Original Research

The medical literature generally recommends moistening the speculum with water for performance of a Papanicolaou (Pap) test, because gel lubricants interfere with specimen analysis and assessment of vaginal secretions.^1,2 After an extensive literature search, we found little information that identified or substantiated the type or frequency of interference or distortion in analysis or assessment with regard to gel lubricants on cervical cytologic evaluation. The only study of gel lubricant use that we found recommended further study because surprisingly few Pap smears are rendered inadequate despite the high prevalence of gel use.³

Due to these findings and the lack of literature substantiating interference or distortion with gel lubricants, we investigated whether there is a difference in Pap smear obscuration rates with gellubricated vs water-lubricated speculum samples.

Methods

Target population

The target population consisted of all women who received Pap smears between 1995 and 1999 at the University of Tennessee Health Sciences Center HealthPlex Family Medicine Residency Program in Memphis, Tennessee. Pap smears were obtained by resident physicians in the Department of Family Medicine, University of Tennessee Health Science Center. The specific technique used by the residents was left to their discretion and each was asked to describe the usual use of lubricants.

More than 4169 Pap smears were identified via Current Procedural Terminology codes (A88141, A88155, A88164, and/or A88167). Of these, 649 charts were selected by using every sixth record. From those selected, 615 contained adequate information to be included in the study.

Data collection

We gathered medical record data by using a retrospective review of medical records, including the medical record number, date of birth, date of service, provider performing pelvic examination or obtaining cervical cytology smear, identification of the laboratory processing and reporting each cytology report, and insurance coverage (Medicare, private, self-payer, and TennCare/ Medicaid). Cervical cytology report information retrieved included sample adequacy (satisfactory or unsatisfactory), whether the sample was identified as obscured, and whether obscuration was caused by blood.

We also collected data from the medical record on potential confounders, including socioeconomic status (determined by insurance source) and reproductive status (currently pregnant, menopausal, or posthysterectomy). Medical records containing incomplete documentation of any portion of the review criteria were excluded.

Analysis

Statistical analysis was completed with SAS 8.1. Simple χ² analysis was used where appropriate to demonstrate associations. A stepwise regression model was considered, but none of the χ² statistics were significant, which eliminated the need for a modeling procedure.

Results

Of the 615 participants, 50 were pregnant, 49 were menopausal, and 42 had undergone a hysterectomy. By matching clinicians’ survey responses to the cytology specimens they collected, we determined that 379 were acquired with water, 81 with gel, and 155 without lubricant.

We reviewed cytology reports for the documented level of adequacy, the presence of any obscuration, and the type of obscuration (see Table). for cytology findings). All 27 obscured and 4 inadequate specimens (5% of the 615 cytology reports reviewed) were reported among women who were pregnant, menopausal, or posthysterectomy. Menopausal women accounted for 89% (24) of obscured specimens and 100% (4) of inadequate specimens. Within the menopausal group, 63% (15) of the specimens were obscured by blood and 37% (9) were obscured by “other.” The term “other” was not defined further or explained on any cytology report. The 5 laboratories reporting obscuration by “other” were contacted, and all reported that this term defines obscuration by nonblood contaminants. Pregnant women accounted for 7% (2) of the obscured specimens, with 1 obscured by blood and 1 obscured by “other.” Women identified as posthysterectomy contributed 4% (1) of the obscured specimens; it was reported as obscured by “other.”

Reports identifying obscured or inadequate specimens and socioeconomic status were also cross-tabulated against type of lubricant used in consideration for possible bias. The outcome showed no identified indication.

No statistically significant difference was found in the likelihood of specimen obscuration or adequacy vs inadequacy between water, gel, or no lubricant. The occurrence of obscuration was lower with the use of water lubricant (3.2%) than with gel lubricant (6.2%) or no lubricant (6.5%). However, this difference was not statistically significant (P<.20).

TABLE
Lubricant use and cytology findings

Discussion

The purpose of this study was to identify any differences in the occurrence of contamination or distortion of cervical cytology test results between water and gel as the lubricant. With a sample size that allowed us to detect an absolute difference as small as 7%, we found no significant difference between the use of gel or water lubricant in the likelihood of cell obscuration or inadequacy. These findings did not support current data reported in several publications and may explain the lack of publications describing specific adverse gel effects on sampling collection.

Inadequate specimens in postmenopausal women

The number of obscured and inadequate specimens found within the group of women who had reached menopause was not unexpected because of hormonal changes in cervical cells and the physical structure of the uterus. Although not unexpected, it is of concern that this group includes many older women who constitute an underscreened subgroup who frequently forego routine cervical cancer screening unless they have gynecologic problems.⁴

In recognizing the need for this group to obtain testing and maintain routine screening compliance, minimizing discomfort related to cervical cell acquisition procedure should be a primary consideration. Because lubricant minimizes friction and optimizes the ease of speculum insertion, gel can be considered an effective choice for these women.

Sampling errors

Nationally, approximately two thirds of false-negative smears are related to inadequate sampling, and the primary sampling error is the failure to obtain cells from the transformational zone, where cancer is known to develop.^5,6 The high percentage of specimen adequacy (99% for the water and gel groups and 100% for the no-lubricant group) found during this study may be attributed to the homogeneity in clinical training of the participating residents.

Although different labs evaluated cytology specimens (depending on the payment source), all providers who performed cervical cell acquisition were considered influenced by similar training. Also, all of our residents are taught that when gel lubricant is used, a thin coat is to be placed only on the external speculum blade surfaces.

Limitations of this study

The size of the study population was limited by medical record completeness and the response rate for physician surveys. A larger study might have found a difference, although it is questionable whether such a difference would be statistically significant.

Reliance on a survey of the usual type of lubricant may be less accurate than direct observation; however, direct observation was not practical in our setting. The adequacy and quality of cytology specimens also could have been affected by cervicitis, vaginitis, interval from last menstrual period, and use of hormone therapy, but these conditions would not be expected to affect the patients of physicians using one type of lubricant more than those using another.

In addition, we were limited in designing the study by the lack of comparison literature. As with other studies of this size, further research is recommended, with additional clinicians and study populations to reinforce and elaborate on the current findings.

Conclusions

A thin coat of water-soluble gel on the external vaginal speculum blade surfaces did not compromise the adequacy or interpretation of cervical cytology. Gel should be considered an option in obtaining Pap smears to ease insertion, minimize discomfort, and perhaps help maintain regular interval sampling compliance. Physicians choosing to use gel should be careful to apply only a thin layer to the outer blades of the speculum.

Corresponding author
Pamela D. Connor, PhD, 66 N. Pauline, Memphis, TN 38163. E-mail: [email protected].

The medical literature generally recommends moistening the speculum with water for performance of a Papanicolaou (Pap) test, because gel lubricants interfere with specimen analysis and assessment of vaginal secretions.^1,2 After an extensive literature search, we found little information that identified or substantiated the type or frequency of interference or distortion in analysis or assessment with regard to gel lubricants on cervical cytologic evaluation. The only study of gel lubricant use that we found recommended further study because surprisingly few Pap smears are rendered inadequate despite the high prevalence of gel use.³

Due to these findings and the lack of literature substantiating interference or distortion with gel lubricants, we investigated whether there is a difference in Pap smear obscuration rates with gellubricated vs water-lubricated speculum samples.

Methods

Target population

The target population consisted of all women who received Pap smears between 1995 and 1999 at the University of Tennessee Health Sciences Center HealthPlex Family Medicine Residency Program in Memphis, Tennessee. Pap smears were obtained by resident physicians in the Department of Family Medicine, University of Tennessee Health Science Center. The specific technique used by the residents was left to their discretion and each was asked to describe the usual use of lubricants.

More than 4169 Pap smears were identified via Current Procedural Terminology codes (A88141, A88155, A88164, and/or A88167). Of these, 649 charts were selected by using every sixth record. From those selected, 615 contained adequate information to be included in the study.

Data collection

We gathered medical record data by using a retrospective review of medical records, including the medical record number, date of birth, date of service, provider performing pelvic examination or obtaining cervical cytology smear, identification of the laboratory processing and reporting each cytology report, and insurance coverage (Medicare, private, self-payer, and TennCare/ Medicaid). Cervical cytology report information retrieved included sample adequacy (satisfactory or unsatisfactory), whether the sample was identified as obscured, and whether obscuration was caused by blood.

We also collected data from the medical record on potential confounders, including socioeconomic status (determined by insurance source) and reproductive status (currently pregnant, menopausal, or posthysterectomy). Medical records containing incomplete documentation of any portion of the review criteria were excluded.

Analysis

Statistical analysis was completed with SAS 8.1. Simple χ² analysis was used where appropriate to demonstrate associations. A stepwise regression model was considered, but none of the χ² statistics were significant, which eliminated the need for a modeling procedure.

Results

Of the 615 participants, 50 were pregnant, 49 were menopausal, and 42 had undergone a hysterectomy. By matching clinicians’ survey responses to the cytology specimens they collected, we determined that 379 were acquired with water, 81 with gel, and 155 without lubricant.

We reviewed cytology reports for the documented level of adequacy, the presence of any obscuration, and the type of obscuration (see Table). for cytology findings). All 27 obscured and 4 inadequate specimens (5% of the 615 cytology reports reviewed) were reported among women who were pregnant, menopausal, or posthysterectomy. Menopausal women accounted for 89% (24) of obscured specimens and 100% (4) of inadequate specimens. Within the menopausal group, 63% (15) of the specimens were obscured by blood and 37% (9) were obscured by “other.” The term “other” was not defined further or explained on any cytology report. The 5 laboratories reporting obscuration by “other” were contacted, and all reported that this term defines obscuration by nonblood contaminants. Pregnant women accounted for 7% (2) of the obscured specimens, with 1 obscured by blood and 1 obscured by “other.” Women identified as posthysterectomy contributed 4% (1) of the obscured specimens; it was reported as obscured by “other.”

Reports identifying obscured or inadequate specimens and socioeconomic status were also cross-tabulated against type of lubricant used in consideration for possible bias. The outcome showed no identified indication.

No statistically significant difference was found in the likelihood of specimen obscuration or adequacy vs inadequacy between water, gel, or no lubricant. The occurrence of obscuration was lower with the use of water lubricant (3.2%) than with gel lubricant (6.2%) or no lubricant (6.5%). However, this difference was not statistically significant (P<.20).

TABLE
Lubricant use and cytology findings

Discussion

The purpose of this study was to identify any differences in the occurrence of contamination or distortion of cervical cytology test results between water and gel as the lubricant. With a sample size that allowed us to detect an absolute difference as small as 7%, we found no significant difference between the use of gel or water lubricant in the likelihood of cell obscuration or inadequacy. These findings did not support current data reported in several publications and may explain the lack of publications describing specific adverse gel effects on sampling collection.

Inadequate specimens in postmenopausal women

The number of obscured and inadequate specimens found within the group of women who had reached menopause was not unexpected because of hormonal changes in cervical cells and the physical structure of the uterus. Although not unexpected, it is of concern that this group includes many older women who constitute an underscreened subgroup who frequently forego routine cervical cancer screening unless they have gynecologic problems.⁴

In recognizing the need for this group to obtain testing and maintain routine screening compliance, minimizing discomfort related to cervical cell acquisition procedure should be a primary consideration. Because lubricant minimizes friction and optimizes the ease of speculum insertion, gel can be considered an effective choice for these women.

Sampling errors

Nationally, approximately two thirds of false-negative smears are related to inadequate sampling, and the primary sampling error is the failure to obtain cells from the transformational zone, where cancer is known to develop.^5,6 The high percentage of specimen adequacy (99% for the water and gel groups and 100% for the no-lubricant group) found during this study may be attributed to the homogeneity in clinical training of the participating residents.

Although different labs evaluated cytology specimens (depending on the payment source), all providers who performed cervical cell acquisition were considered influenced by similar training. Also, all of our residents are taught that when gel lubricant is used, a thin coat is to be placed only on the external speculum blade surfaces.

Limitations of this study

The size of the study population was limited by medical record completeness and the response rate for physician surveys. A larger study might have found a difference, although it is questionable whether such a difference would be statistically significant.

Reliance on a survey of the usual type of lubricant may be less accurate than direct observation; however, direct observation was not practical in our setting. The adequacy and quality of cytology specimens also could have been affected by cervicitis, vaginitis, interval from last menstrual period, and use of hormone therapy, but these conditions would not be expected to affect the patients of physicians using one type of lubricant more than those using another.

In addition, we were limited in designing the study by the lack of comparison literature. As with other studies of this size, further research is recommended, with additional clinicians and study populations to reinforce and elaborate on the current findings.

Conclusions

A thin coat of water-soluble gel on the external vaginal speculum blade surfaces did not compromise the adequacy or interpretation of cervical cytology. Gel should be considered an option in obtaining Pap smears to ease insertion, minimize discomfort, and perhaps help maintain regular interval sampling compliance. Physicians choosing to use gel should be careful to apply only a thin layer to the outer blades of the speculum.

Corresponding author
Pamela D. Connor, PhD, 66 N. Pauline, Memphis, TN 38163. E-mail: [email protected].

The medical literature generally recommends moistening the speculum with water for performance of a Papanicolaou (Pap) test, because gel lubricants interfere with specimen analysis and assessment of vaginal secretions.^1,2 After an extensive literature search, we found little information that identified or substantiated the type or frequency of interference or distortion in analysis or assessment with regard to gel lubricants on cervical cytologic evaluation. The only study of gel lubricant use that we found recommended further study because surprisingly few Pap smears are rendered inadequate despite the high prevalence of gel use.³

Due to these findings and the lack of literature substantiating interference or distortion with gel lubricants, we investigated whether there is a difference in Pap smear obscuration rates with gellubricated vs water-lubricated speculum samples.

Methods

Target population

The target population consisted of all women who received Pap smears between 1995 and 1999 at the University of Tennessee Health Sciences Center HealthPlex Family Medicine Residency Program in Memphis, Tennessee. Pap smears were obtained by resident physicians in the Department of Family Medicine, University of Tennessee Health Science Center. The specific technique used by the residents was left to their discretion and each was asked to describe the usual use of lubricants.

More than 4169 Pap smears were identified via Current Procedural Terminology codes (A88141, A88155, A88164, and/or A88167). Of these, 649 charts were selected by using every sixth record. From those selected, 615 contained adequate information to be included in the study.

Data collection

We gathered medical record data by using a retrospective review of medical records, including the medical record number, date of birth, date of service, provider performing pelvic examination or obtaining cervical cytology smear, identification of the laboratory processing and reporting each cytology report, and insurance coverage (Medicare, private, self-payer, and TennCare/ Medicaid). Cervical cytology report information retrieved included sample adequacy (satisfactory or unsatisfactory), whether the sample was identified as obscured, and whether obscuration was caused by blood.

We also collected data from the medical record on potential confounders, including socioeconomic status (determined by insurance source) and reproductive status (currently pregnant, menopausal, or posthysterectomy). Medical records containing incomplete documentation of any portion of the review criteria were excluded.

Analysis

Statistical analysis was completed with SAS 8.1. Simple χ² analysis was used where appropriate to demonstrate associations. A stepwise regression model was considered, but none of the χ² statistics were significant, which eliminated the need for a modeling procedure.

Results

Of the 615 participants, 50 were pregnant, 49 were menopausal, and 42 had undergone a hysterectomy. By matching clinicians’ survey responses to the cytology specimens they collected, we determined that 379 were acquired with water, 81 with gel, and 155 without lubricant.

We reviewed cytology reports for the documented level of adequacy, the presence of any obscuration, and the type of obscuration (see Table). for cytology findings). All 27 obscured and 4 inadequate specimens (5% of the 615 cytology reports reviewed) were reported among women who were pregnant, menopausal, or posthysterectomy. Menopausal women accounted for 89% (24) of obscured specimens and 100% (4) of inadequate specimens. Within the menopausal group, 63% (15) of the specimens were obscured by blood and 37% (9) were obscured by “other.” The term “other” was not defined further or explained on any cytology report. The 5 laboratories reporting obscuration by “other” were contacted, and all reported that this term defines obscuration by nonblood contaminants. Pregnant women accounted for 7% (2) of the obscured specimens, with 1 obscured by blood and 1 obscured by “other.” Women identified as posthysterectomy contributed 4% (1) of the obscured specimens; it was reported as obscured by “other.”

Reports identifying obscured or inadequate specimens and socioeconomic status were also cross-tabulated against type of lubricant used in consideration for possible bias. The outcome showed no identified indication.

No statistically significant difference was found in the likelihood of specimen obscuration or adequacy vs inadequacy between water, gel, or no lubricant. The occurrence of obscuration was lower with the use of water lubricant (3.2%) than with gel lubricant (6.2%) or no lubricant (6.5%). However, this difference was not statistically significant (P<.20).

TABLE
Lubricant use and cytology findings

Discussion

The purpose of this study was to identify any differences in the occurrence of contamination or distortion of cervical cytology test results between water and gel as the lubricant. With a sample size that allowed us to detect an absolute difference as small as 7%, we found no significant difference between the use of gel or water lubricant in the likelihood of cell obscuration or inadequacy. These findings did not support current data reported in several publications and may explain the lack of publications describing specific adverse gel effects on sampling collection.

Inadequate specimens in postmenopausal women

The number of obscured and inadequate specimens found within the group of women who had reached menopause was not unexpected because of hormonal changes in cervical cells and the physical structure of the uterus. Although not unexpected, it is of concern that this group includes many older women who constitute an underscreened subgroup who frequently forego routine cervical cancer screening unless they have gynecologic problems.⁴

In recognizing the need for this group to obtain testing and maintain routine screening compliance, minimizing discomfort related to cervical cell acquisition procedure should be a primary consideration. Because lubricant minimizes friction and optimizes the ease of speculum insertion, gel can be considered an effective choice for these women.

Sampling errors

Nationally, approximately two thirds of false-negative smears are related to inadequate sampling, and the primary sampling error is the failure to obtain cells from the transformational zone, where cancer is known to develop.^5,6 The high percentage of specimen adequacy (99% for the water and gel groups and 100% for the no-lubricant group) found during this study may be attributed to the homogeneity in clinical training of the participating residents.

Although different labs evaluated cytology specimens (depending on the payment source), all providers who performed cervical cell acquisition were considered influenced by similar training. Also, all of our residents are taught that when gel lubricant is used, a thin coat is to be placed only on the external speculum blade surfaces.

Limitations of this study

The size of the study population was limited by medical record completeness and the response rate for physician surveys. A larger study might have found a difference, although it is questionable whether such a difference would be statistically significant.

Reliance on a survey of the usual type of lubricant may be less accurate than direct observation; however, direct observation was not practical in our setting. The adequacy and quality of cytology specimens also could have been affected by cervicitis, vaginitis, interval from last menstrual period, and use of hormone therapy, but these conditions would not be expected to affect the patients of physicians using one type of lubricant more than those using another.

In addition, we were limited in designing the study by the lack of comparison literature. As with other studies of this size, further research is recommended, with additional clinicians and study populations to reinforce and elaborate on the current findings.

Conclusions

A thin coat of water-soluble gel on the external vaginal speculum blade surfaces did not compromise the adequacy or interpretation of cervical cytology. Gel should be considered an option in obtaining Pap smears to ease insertion, minimize discomfort, and perhaps help maintain regular interval sampling compliance. Physicians choosing to use gel should be careful to apply only a thin layer to the outer blades of the speculum.

Corresponding author
Pamela D. Connor, PhD, 66 N. Pauline, Memphis, TN 38163. E-mail: [email protected].

To evaluate psychostimulants in the treatment of attention deficit–hyperactivity disorder (ADHD), predominantly inattentive subtype with coexisting academic impairment, a consecutive sample of 35 students from a private, primary care, office-based practice was followed for 1 year. All participants received psychostimulants, multimodal interventions, and treatment of comorbid disorders. Baseline mean grade-point averages (GPAs) from the preceding school year were compared with mean GPAs calculated at 1 year. Statistical analysis was by a paired samples t test.

Of 32 students who completed the study, 27 pupils’ GPAs did not improve (84.4%), while 5 pupils’ GPAs did improve (15.6%) (P=.176).

These findings call for additional research to further define predominantly inattentive ADHD in patients who present with inattention and academic concerns, and the role of stimulants in the treatment of this disorder.

Diagnostic criteria

In 1994, the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) redefined the full syndrome of attention deficit hyperactivity disorder as combined ADHD, and introduced 2 new subtypes: predominantly inattentive and predominantly hyperactive-impulsive.¹ Since publication, the majority of new cases identified by DSM-IV have been predominantly inattentive ADHD.² Primary care physicians manage 86% of patients with ADHD.³

The clinical issues

The diagnostic criteria defining predominantly inattentive ADHD and the evidence supporting its inclusion as a separate subtype mainly involve students with academic impairment.⁴ Measuring the effect of pharmacologic intervention on ADHD and academic functioning is important.^5,6

Research on the use of psychostimulants in patients with attention deficit disorder without hyperactivity as defined by the DSM-III⁷ showed a high rate of nonresponders and no evidence of long-term effects on academic achievement and learning.^8-10 It is not clear whether these results apply to patients with predominantly inattentive ADHD.¹¹ A recent National Institutes of Health Consensus Statement acknowledged the need for research that specifically targets predominantly inattentive ADHD and the effects of psychotropic therapy on school performance associated with the subtype.¹²

The following study was therefore designed to address these issues and determine the effect of psychostimulant treatment in patients with predominantly inattentive ADHD and academic impairment.

Methods

The 35 participants from the author’s rural, office-based practice, seen because of academic concerns and inattention, were consecutively diagnosed with predominantly inattentive ADHD based on information obtained from parents and teachers and application of the DSM-IV criteria.¹ Clinical examinations ruled out physical or neurologic handicaps and uncorrected visual or hearing impairments ( Table 1).

Seven participants had academic impairment as the only comorbidity with predominantly inattentive ADHD. Twenty-eight had multiple comorbidities. These included anxiety symptoms (12), dysgraphia (12), psychosomatic complaints (11), social problems (6), communication disorders (4), learning disabilities (3), enuresis (3), and dysphoria (3). Six parents of the students had a history of anxiety–depression and 2 had generalized anxiety disorder.

Anxiety symptoms, psychosomatic complaints, dysphoria, and fine-motor dyspraxia were descriptive problems and not considered disorders using DSM-IV criteria.¹ Learning disabilities and communication disorders were diagnosed by school psychologists and speech language pathologists, respectively. Social impairment was diagnosed using the asocial domain on the Conner’s Teacher Rating Scale¹³ and noting t scores of ≥1.5 standard deviations above the mean. Enuresis was diagnosed from information obtained from the history and physical exam. None of the cohort met DSM-IV criteria for oppositional defiant disorder or conduct disorder.¹

The diagnostic protocol for ADHD and coexisting disorders used in this study was consistent with the recommendations endorsed by the American Academy of Pediatrics and the American Academy of Family Physicians.¹⁴

The baseline GPA for each participant was determined by taking the GPA from each report card of the preceding school year (either four 9-week report cards or six 6-week report cards) and calculating the mean GPA. The mean GPA after the school year following psychostimulant therapy was calculated for each student in the same manner and compared with his mean baseline GPA.

Participants were assessed every 6 to 9 weeks (when they brought their report cards to the office) for compliance and possible side effects of medication. Dosage adjustments were determined by using follow-up information obtained from parents and teachers, based on DSM-IV criteria for predominantly inattentive ADHD.

All patients, families, and school personnel received educational information on predominantly inattentive ADHD throughout the study. This is consistent with the practice parameters for ADHD from the American Academy of Child and Adolescent Psychiatry and a national perspective on ADHD treatment in primary care practice settings, which states: “providing information about symptoms of ADHD, areas of impairment, etiology, and principles of behavior management to parents and teachers constitutes sound clinical practice.”¹⁵ Statistical analysis was performed by a paired samples t test.

TABLE 1
Profile of participants in study of ADHD treatment and academic performance

Results

Thirty-two of 35 students completed the study. Using a Mann-Whitney U test, no significant differences were found between these patients and those who did not complete the study (P=.80 for baseline GPA differences and P=.80 for age.)

According to follow-up information from parents and teachers, all participants exhibited short-term improvements in DSM-IV criteria for predominantly inattentive ADHD at some point during the study. Five pupils who completed the study had improved GPAs (15.6%), while the remaining 27 participants showed no change or decreased GPAs (84.4%).

Using students t tests to compare age, baseline GPAs, and number of comorbidities and χ² for parental psychopathology, no significant differences were found between students with improved GPAs and those without improvement in their GPAs (P=.61 for age, P=.93 for baseline GPA differences, P=.53 for differences in comorbidities, and P=.70 for differences in parental psychopathology; see Table 1). Using a paired sample t test on data from all 32 participants showed that the overall treatment effect was not significant (P=.176; see Table 2).

TABLE 2
Grade-point averages at baseline and at the study’s conclusion*

Discussion

Psychostimulant therapy did not significantly improve the outcome measures (GPAs) in the cohort diagnosed with predominantly inattentive ADHD and academic impairment. Additional comorbidities were diagnosed and treated, but differences among participants were not statistically significant. Short-term decreases in DSM-IV symptoms of predominantly inattentive ADHD did not translate into academic gains.

Limitations to the present study include the small sample size and lack of a control group. Thus, the findings should be considered preliminary. GPAs are not standardized scores and are sensitive to varying influences. However, the American Academy of Pediatrics notes that even when standardized instruments are used to assess stimulant treatment for ADHD, there is “frequently no association with improvements in academic achievement.”¹⁶ Only short-term gains in academic efficiency have been reported.¹⁷

The average doses employed (methylphenidate 16.7 mg/d, dextroamphetamine 11 mg/d) were smaller than the starting doses used successfully in the Multimodal Treatment Study of Children with ADHD (methylphenidate 30.5 mg/d, dextroamphetamine 15.25 mg/d).¹⁸ However, this study excluded patients with predominantly inattentive ADHD.¹⁹ The lower dosages used in the present study are compatible with the practice parameters of the American Academy of Child and Adolescent Psychiatry for ADHD without hyperactivity.²⁰

All participants in the study received educational assistance. Those students not attending resource classes qualified for accommodations and modifications under Section 504 of the Rehabilitation Act of 1973 guidelines. The small sample sizes precluded an analysis of the effects of these different educational interventions on GPAs. The input from multiple teachers and classroom settings could not be delineated. However, GPAs have the advantage of being readily accessible. In addition, the findings obtained from a community-based practice with patients and families in their natural environment support the study’s results.

How do the results of the present study correlate with the literature on predominantly inattentive ADHD, and how should clinicians incorporate these data into their evaluations of students who have inattention and academic concerns? Results from the Pediatric Research in Office Settings and the Ambulatory Sentinel Practice Network²¹ note that there is “a lack of standardization in the primary care evaluation of attentional problems.” Inattention is not unique to predominantly inattentive ADHD. Children and adolescents with language/learning disorders,^22-24 anxiety/depression,²⁵ and family dysfunction²⁶ are also described as inattentive.

It is difficult to define accurately what is meant by inattention in predominantly inattentive ADHD because the psychological construct of attention is not the same as that being measured behaviorally in predominantly inattentive ADHD.²⁷ In addition, the unifying theory on ADHD, which involves deficits in behavior inhibition and executive function, does not include predominantly inattentive ADHD in the definition.^28,29 The American Academy of Pediatrics concludes that with ADHD the need “to develop more valid and precise diagnostic criteria is essential.”³⁰

The present study should be considered an introductory step in the evaluation of psychostimulant treatment in predominantly inattentive ADHD. GPAs are easily obtained by busy clinicians and are time-efficient measures of treatment outcomes. Clearly, additional research, using larger groups and controls, is needed.

ACKNOWLEDGMENTS

The author thanks Glenn N. Jones, PhD, for his assistance with the statistical analysis.

To evaluate psychostimulants in the treatment of attention deficit–hyperactivity disorder (ADHD), predominantly inattentive subtype with coexisting academic impairment, a consecutive sample of 35 students from a private, primary care, office-based practice was followed for 1 year. All participants received psychostimulants, multimodal interventions, and treatment of comorbid disorders. Baseline mean grade-point averages (GPAs) from the preceding school year were compared with mean GPAs calculated at 1 year. Statistical analysis was by a paired samples t test.

Of 32 students who completed the study, 27 pupils’ GPAs did not improve (84.4%), while 5 pupils’ GPAs did improve (15.6%) (P=.176).

These findings call for additional research to further define predominantly inattentive ADHD in patients who present with inattention and academic concerns, and the role of stimulants in the treatment of this disorder.

Diagnostic criteria

In 1994, the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) redefined the full syndrome of attention deficit hyperactivity disorder as combined ADHD, and introduced 2 new subtypes: predominantly inattentive and predominantly hyperactive-impulsive.¹ Since publication, the majority of new cases identified by DSM-IV have been predominantly inattentive ADHD.² Primary care physicians manage 86% of patients with ADHD.³

The clinical issues

The diagnostic criteria defining predominantly inattentive ADHD and the evidence supporting its inclusion as a separate subtype mainly involve students with academic impairment.⁴ Measuring the effect of pharmacologic intervention on ADHD and academic functioning is important.^5,6

Research on the use of psychostimulants in patients with attention deficit disorder without hyperactivity as defined by the DSM-III⁷ showed a high rate of nonresponders and no evidence of long-term effects on academic achievement and learning.^8-10 It is not clear whether these results apply to patients with predominantly inattentive ADHD.¹¹ A recent National Institutes of Health Consensus Statement acknowledged the need for research that specifically targets predominantly inattentive ADHD and the effects of psychotropic therapy on school performance associated with the subtype.¹²

The following study was therefore designed to address these issues and determine the effect of psychostimulant treatment in patients with predominantly inattentive ADHD and academic impairment.

Methods

The 35 participants from the author’s rural, office-based practice, seen because of academic concerns and inattention, were consecutively diagnosed with predominantly inattentive ADHD based on information obtained from parents and teachers and application of the DSM-IV criteria.¹ Clinical examinations ruled out physical or neurologic handicaps and uncorrected visual or hearing impairments ( Table 1).

Seven participants had academic impairment as the only comorbidity with predominantly inattentive ADHD. Twenty-eight had multiple comorbidities. These included anxiety symptoms (12), dysgraphia (12), psychosomatic complaints (11), social problems (6), communication disorders (4), learning disabilities (3), enuresis (3), and dysphoria (3). Six parents of the students had a history of anxiety–depression and 2 had generalized anxiety disorder.

Anxiety symptoms, psychosomatic complaints, dysphoria, and fine-motor dyspraxia were descriptive problems and not considered disorders using DSM-IV criteria.¹ Learning disabilities and communication disorders were diagnosed by school psychologists and speech language pathologists, respectively. Social impairment was diagnosed using the asocial domain on the Conner’s Teacher Rating Scale¹³ and noting t scores of ≥1.5 standard deviations above the mean. Enuresis was diagnosed from information obtained from the history and physical exam. None of the cohort met DSM-IV criteria for oppositional defiant disorder or conduct disorder.¹

The diagnostic protocol for ADHD and coexisting disorders used in this study was consistent with the recommendations endorsed by the American Academy of Pediatrics and the American Academy of Family Physicians.¹⁴

The baseline GPA for each participant was determined by taking the GPA from each report card of the preceding school year (either four 9-week report cards or six 6-week report cards) and calculating the mean GPA. The mean GPA after the school year following psychostimulant therapy was calculated for each student in the same manner and compared with his mean baseline GPA.

Participants were assessed every 6 to 9 weeks (when they brought their report cards to the office) for compliance and possible side effects of medication. Dosage adjustments were determined by using follow-up information obtained from parents and teachers, based on DSM-IV criteria for predominantly inattentive ADHD.

All patients, families, and school personnel received educational information on predominantly inattentive ADHD throughout the study. This is consistent with the practice parameters for ADHD from the American Academy of Child and Adolescent Psychiatry and a national perspective on ADHD treatment in primary care practice settings, which states: “providing information about symptoms of ADHD, areas of impairment, etiology, and principles of behavior management to parents and teachers constitutes sound clinical practice.”¹⁵ Statistical analysis was performed by a paired samples t test.

TABLE 1
Profile of participants in study of ADHD treatment and academic performance

Results

Thirty-two of 35 students completed the study. Using a Mann-Whitney U test, no significant differences were found between these patients and those who did not complete the study (P=.80 for baseline GPA differences and P=.80 for age.)

According to follow-up information from parents and teachers, all participants exhibited short-term improvements in DSM-IV criteria for predominantly inattentive ADHD at some point during the study. Five pupils who completed the study had improved GPAs (15.6%), while the remaining 27 participants showed no change or decreased GPAs (84.4%).

Using students t tests to compare age, baseline GPAs, and number of comorbidities and χ² for parental psychopathology, no significant differences were found between students with improved GPAs and those without improvement in their GPAs (P=.61 for age, P=.93 for baseline GPA differences, P=.53 for differences in comorbidities, and P=.70 for differences in parental psychopathology; see Table 1). Using a paired sample t test on data from all 32 participants showed that the overall treatment effect was not significant (P=.176; see Table 2).

TABLE 2
Grade-point averages at baseline and at the study’s conclusion*

Discussion

Psychostimulant therapy did not significantly improve the outcome measures (GPAs) in the cohort diagnosed with predominantly inattentive ADHD and academic impairment. Additional comorbidities were diagnosed and treated, but differences among participants were not statistically significant. Short-term decreases in DSM-IV symptoms of predominantly inattentive ADHD did not translate into academic gains.

Limitations to the present study include the small sample size and lack of a control group. Thus, the findings should be considered preliminary. GPAs are not standardized scores and are sensitive to varying influences. However, the American Academy of Pediatrics notes that even when standardized instruments are used to assess stimulant treatment for ADHD, there is “frequently no association with improvements in academic achievement.”¹⁶ Only short-term gains in academic efficiency have been reported.¹⁷

The average doses employed (methylphenidate 16.7 mg/d, dextroamphetamine 11 mg/d) were smaller than the starting doses used successfully in the Multimodal Treatment Study of Children with ADHD (methylphenidate 30.5 mg/d, dextroamphetamine 15.25 mg/d).¹⁸ However, this study excluded patients with predominantly inattentive ADHD.¹⁹ The lower dosages used in the present study are compatible with the practice parameters of the American Academy of Child and Adolescent Psychiatry for ADHD without hyperactivity.²⁰

All participants in the study received educational assistance. Those students not attending resource classes qualified for accommodations and modifications under Section 504 of the Rehabilitation Act of 1973 guidelines. The small sample sizes precluded an analysis of the effects of these different educational interventions on GPAs. The input from multiple teachers and classroom settings could not be delineated. However, GPAs have the advantage of being readily accessible. In addition, the findings obtained from a community-based practice with patients and families in their natural environment support the study’s results.

How do the results of the present study correlate with the literature on predominantly inattentive ADHD, and how should clinicians incorporate these data into their evaluations of students who have inattention and academic concerns? Results from the Pediatric Research in Office Settings and the Ambulatory Sentinel Practice Network²¹ note that there is “a lack of standardization in the primary care evaluation of attentional problems.” Inattention is not unique to predominantly inattentive ADHD. Children and adolescents with language/learning disorders,^22-24 anxiety/depression,²⁵ and family dysfunction²⁶ are also described as inattentive.

It is difficult to define accurately what is meant by inattention in predominantly inattentive ADHD because the psychological construct of attention is not the same as that being measured behaviorally in predominantly inattentive ADHD.²⁷ In addition, the unifying theory on ADHD, which involves deficits in behavior inhibition and executive function, does not include predominantly inattentive ADHD in the definition.^28,29 The American Academy of Pediatrics concludes that with ADHD the need “to develop more valid and precise diagnostic criteria is essential.”³⁰

The present study should be considered an introductory step in the evaluation of psychostimulant treatment in predominantly inattentive ADHD. GPAs are easily obtained by busy clinicians and are time-efficient measures of treatment outcomes. Clearly, additional research, using larger groups and controls, is needed.

ACKNOWLEDGMENTS

The author thanks Glenn N. Jones, PhD, for his assistance with the statistical analysis.

To evaluate psychostimulants in the treatment of attention deficit–hyperactivity disorder (ADHD), predominantly inattentive subtype with coexisting academic impairment, a consecutive sample of 35 students from a private, primary care, office-based practice was followed for 1 year. All participants received psychostimulants, multimodal interventions, and treatment of comorbid disorders. Baseline mean grade-point averages (GPAs) from the preceding school year were compared with mean GPAs calculated at 1 year. Statistical analysis was by a paired samples t test.

Of 32 students who completed the study, 27 pupils’ GPAs did not improve (84.4%), while 5 pupils’ GPAs did improve (15.6%) (P=.176).

These findings call for additional research to further define predominantly inattentive ADHD in patients who present with inattention and academic concerns, and the role of stimulants in the treatment of this disorder.

Diagnostic criteria

In 1994, the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) redefined the full syndrome of attention deficit hyperactivity disorder as combined ADHD, and introduced 2 new subtypes: predominantly inattentive and predominantly hyperactive-impulsive.¹ Since publication, the majority of new cases identified by DSM-IV have been predominantly inattentive ADHD.² Primary care physicians manage 86% of patients with ADHD.³

The clinical issues

The diagnostic criteria defining predominantly inattentive ADHD and the evidence supporting its inclusion as a separate subtype mainly involve students with academic impairment.⁴ Measuring the effect of pharmacologic intervention on ADHD and academic functioning is important.^5,6

Research on the use of psychostimulants in patients with attention deficit disorder without hyperactivity as defined by the DSM-III⁷ showed a high rate of nonresponders and no evidence of long-term effects on academic achievement and learning.^8-10 It is not clear whether these results apply to patients with predominantly inattentive ADHD.¹¹ A recent National Institutes of Health Consensus Statement acknowledged the need for research that specifically targets predominantly inattentive ADHD and the effects of psychotropic therapy on school performance associated with the subtype.¹²

The following study was therefore designed to address these issues and determine the effect of psychostimulant treatment in patients with predominantly inattentive ADHD and academic impairment.

Methods

The 35 participants from the author’s rural, office-based practice, seen because of academic concerns and inattention, were consecutively diagnosed with predominantly inattentive ADHD based on information obtained from parents and teachers and application of the DSM-IV criteria.¹ Clinical examinations ruled out physical or neurologic handicaps and uncorrected visual or hearing impairments ( Table 1).

Seven participants had academic impairment as the only comorbidity with predominantly inattentive ADHD. Twenty-eight had multiple comorbidities. These included anxiety symptoms (12), dysgraphia (12), psychosomatic complaints (11), social problems (6), communication disorders (4), learning disabilities (3), enuresis (3), and dysphoria (3). Six parents of the students had a history of anxiety–depression and 2 had generalized anxiety disorder.

Anxiety symptoms, psychosomatic complaints, dysphoria, and fine-motor dyspraxia were descriptive problems and not considered disorders using DSM-IV criteria.¹ Learning disabilities and communication disorders were diagnosed by school psychologists and speech language pathologists, respectively. Social impairment was diagnosed using the asocial domain on the Conner’s Teacher Rating Scale¹³ and noting t scores of ≥1.5 standard deviations above the mean. Enuresis was diagnosed from information obtained from the history and physical exam. None of the cohort met DSM-IV criteria for oppositional defiant disorder or conduct disorder.¹

The diagnostic protocol for ADHD and coexisting disorders used in this study was consistent with the recommendations endorsed by the American Academy of Pediatrics and the American Academy of Family Physicians.¹⁴

The baseline GPA for each participant was determined by taking the GPA from each report card of the preceding school year (either four 9-week report cards or six 6-week report cards) and calculating the mean GPA. The mean GPA after the school year following psychostimulant therapy was calculated for each student in the same manner and compared with his mean baseline GPA.

Participants were assessed every 6 to 9 weeks (when they brought their report cards to the office) for compliance and possible side effects of medication. Dosage adjustments were determined by using follow-up information obtained from parents and teachers, based on DSM-IV criteria for predominantly inattentive ADHD.

All patients, families, and school personnel received educational information on predominantly inattentive ADHD throughout the study. This is consistent with the practice parameters for ADHD from the American Academy of Child and Adolescent Psychiatry and a national perspective on ADHD treatment in primary care practice settings, which states: “providing information about symptoms of ADHD, areas of impairment, etiology, and principles of behavior management to parents and teachers constitutes sound clinical practice.”¹⁵ Statistical analysis was performed by a paired samples t test.

TABLE 1
Profile of participants in study of ADHD treatment and academic performance

Results

Thirty-two of 35 students completed the study. Using a Mann-Whitney U test, no significant differences were found between these patients and those who did not complete the study (P=.80 for baseline GPA differences and P=.80 for age.)

According to follow-up information from parents and teachers, all participants exhibited short-term improvements in DSM-IV criteria for predominantly inattentive ADHD at some point during the study. Five pupils who completed the study had improved GPAs (15.6%), while the remaining 27 participants showed no change or decreased GPAs (84.4%).

Using students t tests to compare age, baseline GPAs, and number of comorbidities and χ² for parental psychopathology, no significant differences were found between students with improved GPAs and those without improvement in their GPAs (P=.61 for age, P=.93 for baseline GPA differences, P=.53 for differences in comorbidities, and P=.70 for differences in parental psychopathology; see Table 1). Using a paired sample t test on data from all 32 participants showed that the overall treatment effect was not significant (P=.176; see Table 2).

TABLE 2
Grade-point averages at baseline and at the study’s conclusion*

Discussion

Psychostimulant therapy did not significantly improve the outcome measures (GPAs) in the cohort diagnosed with predominantly inattentive ADHD and academic impairment. Additional comorbidities were diagnosed and treated, but differences among participants were not statistically significant. Short-term decreases in DSM-IV symptoms of predominantly inattentive ADHD did not translate into academic gains.

Limitations to the present study include the small sample size and lack of a control group. Thus, the findings should be considered preliminary. GPAs are not standardized scores and are sensitive to varying influences. However, the American Academy of Pediatrics notes that even when standardized instruments are used to assess stimulant treatment for ADHD, there is “frequently no association with improvements in academic achievement.”¹⁶ Only short-term gains in academic efficiency have been reported.¹⁷

The average doses employed (methylphenidate 16.7 mg/d, dextroamphetamine 11 mg/d) were smaller than the starting doses used successfully in the Multimodal Treatment Study of Children with ADHD (methylphenidate 30.5 mg/d, dextroamphetamine 15.25 mg/d).¹⁸ However, this study excluded patients with predominantly inattentive ADHD.¹⁹ The lower dosages used in the present study are compatible with the practice parameters of the American Academy of Child and Adolescent Psychiatry for ADHD without hyperactivity.²⁰

All participants in the study received educational assistance. Those students not attending resource classes qualified for accommodations and modifications under Section 504 of the Rehabilitation Act of 1973 guidelines. The small sample sizes precluded an analysis of the effects of these different educational interventions on GPAs. The input from multiple teachers and classroom settings could not be delineated. However, GPAs have the advantage of being readily accessible. In addition, the findings obtained from a community-based practice with patients and families in their natural environment support the study’s results.

How do the results of the present study correlate with the literature on predominantly inattentive ADHD, and how should clinicians incorporate these data into their evaluations of students who have inattention and academic concerns? Results from the Pediatric Research in Office Settings and the Ambulatory Sentinel Practice Network²¹ note that there is “a lack of standardization in the primary care evaluation of attentional problems.” Inattention is not unique to predominantly inattentive ADHD. Children and adolescents with language/learning disorders,^22-24 anxiety/depression,²⁵ and family dysfunction²⁶ are also described as inattentive.

It is difficult to define accurately what is meant by inattention in predominantly inattentive ADHD because the psychological construct of attention is not the same as that being measured behaviorally in predominantly inattentive ADHD.²⁷ In addition, the unifying theory on ADHD, which involves deficits in behavior inhibition and executive function, does not include predominantly inattentive ADHD in the definition.^28,29 The American Academy of Pediatrics concludes that with ADHD the need “to develop more valid and precise diagnostic criteria is essential.”³⁰

The present study should be considered an introductory step in the evaluation of psychostimulant treatment in predominantly inattentive ADHD. GPAs are easily obtained by busy clinicians and are time-efficient measures of treatment outcomes. Clearly, additional research, using larger groups and controls, is needed.

ACKNOWLEDGMENTS

The author thanks Glenn N. Jones, PhD, for his assistance with the statistical analysis.

With escalating health care costs, primary care physicians need a simple way to monitor and modify the highusing behavior of their managed care patients. Several studies have shown that <20% of a primary care physician’s patient load will use 90% of the expended resources each year.¹ Although many of these expenditures may be unavoidable due to acute injury or illness, many of these high-users are patients with chronic illnesses.

Most efforts to contain costs have focused on developing clinical care protocols for expensive illnesses (ie, coronary heart failure, diabetes)² to reduce the need for inpatient management. Also, health maintenance organizations (HMOs) have developed incentive plans for physicians who hold down costs by reducing use of high-cost services.³ Several studies have shown that when realtime databases are used and available for feedback to physicians, quality improves and cost is contained.^4,5

Other than descriptions of disease-focused case management, there is little information in the literature on methods primary care physicians can use themselves to monitor patients’ use patterns. Our recent study showed that physicians are often unaware of the activity of some of their highest-using patients and miss the opportunity to intervene.⁶

We conducted a randomized prospective trial comparing 3 different interventions that primary care physicians can use to monitor and modify their patients’ resource use patterns. The goal of this study was to find a relatively simple method that would be accepted by primary care physicians to lower high-cost encounters among their highest users of medical services.

Methods

Study sample

Sixteen primary care physicians—employed at least 5 years at 4 different satellite clinics of a large multispecialty clinic—were randomly divided into a 4-member control group and three 4-member intervention groups. Two-year retrospective financial data of each physician’s patient load were analyzed to determine which patients had been among the top 10% in resource use each of the last 2 years.

From the resulting group of 3200 patients, 100 patients of each primary care physician were chosen randomly to be followed for 1 year, along with their primary care physician in the 4-member groups. All 1600 cases were available for analysis, maintaining health plan enrollment throughout the study period. Fourteen patients died during the study period. Health plan financial data and clinic visit data were used. Table 1 shows physician and patient demographics.

TABLE 1
Physician and patient demographics

Study design

Patients’ health care use for the study period was tracked through the information system of the multispecialty clinic. It was confirmed by reviewing charge data from the patients’ HMO billing record.

Data were analyzed on a quarterly basis, and then compiled for an annual figure at the end of the study. At the end of the study, all physicians in the 3 intervention groups (n=12) were surveyed about their acceptance of incorporating moderate or maximal intervention into their clinical practice. This study was approved by the Institutional Review Board.

The control group was unaware of the study and had no contact with study personnel until the study was completed. The 3 intervention groups were divided into minimal, moderate, and maximal intervention.

Minimal intervention. Primary care physicians received a list of 100 of their patients designated as high users with identifying information. General suggestions were given to primary care physicians on how they could monitor/modify high users’ behavior: make regular appointments, have the nurse call for follow-up after an emergency department visit or hospital admission.

Moderate intervention. Primary care physicians received the initial list and quarterly updates of patients on their lists who had an emergency department visit or inpatient admission or did not follow-up with them in the clinic within 2 weeks of the high-cost encounter.

Maximal intervention. Intervention in the maximal group was the same as for moderate intervention, except that patients who did not make a follow-up visit within 2 weeks were contacted by a case manager to determine barriers to access and to facilitate a follow-up visit with the primary care physician. Where appropriate, a follow-up visit was made with the primary care physician by the case manager.

Outcome measures

Emergency department visits and inpatient admissions were designated as high-cost encounters because of their potential for high use, accounting for a significant portion of non-surgical cost for HMO members, and a high likelihood of lack of follow-up after the encounter. Review of HMO financial data revealed these to be members’ highest (nonsurgical) costs. A calculated variable: A high-cost encounter was calculated by determining a binary outcome variable derived by aggregating emergency department and inpatient visits.

Data analysis

The study groups were compared by logistic regression. The 95% confidence intervals (CIs) accompanying the odds ratios (ORs) are the tests of significance. If the range of the CI includes the value 1, the difference between groups being compared is not statistically significant (α=.05).

Results

Table 2 shows the OR of a high-cost encounter (emergency department visit or inpatient admission) for each intervention group. The unit of measure for this table is patient-months.^7,8 All ORs are read from left to right. For example, the minimal intervention group is 2.19 times more likely to have an emergency department event than maximal group.

The risk of a high-cost encounter was significantly greater for the minimal intervention than for the moderate or maximal intervention groups. The moderate group had a statistically significant greater risk of a high-cost encounter than the maximal intervention group, but the observed magnitude of the risk was small and the lower limit of the CI is very close to 1. The clinical importance of this finding may be questioned in light of the cost effectiveness of the maximal intervention.

The probability of an emergency department visit was significantly reduced for minimal compared with moderate and maximal intervention. The risk for emergency department events was the same for the moderate and maximal intervention groups.

The minimal group was more likely to have an admission than both the moderate and maximal intervention groups. The maximal group was also less likely to have an admission than the moderate intervention group. The moderate intervention appears to be the most costeffective because of reductions achieved with minimal staff involvement.

TABLE 2
Odds ratio of high-cost encounter* for each intervention group

Physician acceptance

All physicians in the 3 intervention groups were surveyed after study completion. Ninety percent agreed with the statement “I will use the moderate intervention now that it is shown to reduce utilization.”

Maximal intervention was thought to be less useful because many patients contacted were under the care of specialists and had no intention of returning to the primary care physician for care. Most of these patients did not require the use of the care manager, so the primary care physicians considered this extra expense as unnecessary.

Discussion

Our results appear to support the contention that primary care physicians can use relatively simple methods to monitor and modify the highuse behavior of members of their managed care panels. By designating frequent users of medical services as “high risk” for future utilization, primary care physicians can track these patients in a proactive fashion using a real-time database system.

At least in this relatively large, vertically integrated, multispecialty health system, emergency department and inpatient admissions were significantly reduced using the database. The moderate intervention appeared to be relatively well accepted by the primary care physicians and able to be instituted within their practice without much difficulty.

If adopted by larger health care systems, this method should result in considerable savings. Other studies in different health care settings are needed before this method can be recommended on a wider basis.

With escalating health care costs, primary care physicians need a simple way to monitor and modify the highusing behavior of their managed care patients. Several studies have shown that <20% of a primary care physician’s patient load will use 90% of the expended resources each year.¹ Although many of these expenditures may be unavoidable due to acute injury or illness, many of these high-users are patients with chronic illnesses.

Most efforts to contain costs have focused on developing clinical care protocols for expensive illnesses (ie, coronary heart failure, diabetes)² to reduce the need for inpatient management. Also, health maintenance organizations (HMOs) have developed incentive plans for physicians who hold down costs by reducing use of high-cost services.³ Several studies have shown that when realtime databases are used and available for feedback to physicians, quality improves and cost is contained.^4,5

Other than descriptions of disease-focused case management, there is little information in the literature on methods primary care physicians can use themselves to monitor patients’ use patterns. Our recent study showed that physicians are often unaware of the activity of some of their highest-using patients and miss the opportunity to intervene.⁶

We conducted a randomized prospective trial comparing 3 different interventions that primary care physicians can use to monitor and modify their patients’ resource use patterns. The goal of this study was to find a relatively simple method that would be accepted by primary care physicians to lower high-cost encounters among their highest users of medical services.

Methods

Study sample

Sixteen primary care physicians—employed at least 5 years at 4 different satellite clinics of a large multispecialty clinic—were randomly divided into a 4-member control group and three 4-member intervention groups. Two-year retrospective financial data of each physician’s patient load were analyzed to determine which patients had been among the top 10% in resource use each of the last 2 years.

From the resulting group of 3200 patients, 100 patients of each primary care physician were chosen randomly to be followed for 1 year, along with their primary care physician in the 4-member groups. All 1600 cases were available for analysis, maintaining health plan enrollment throughout the study period. Fourteen patients died during the study period. Health plan financial data and clinic visit data were used. Table 1 shows physician and patient demographics.

TABLE 1
Physician and patient demographics

Study design

Patients’ health care use for the study period was tracked through the information system of the multispecialty clinic. It was confirmed by reviewing charge data from the patients’ HMO billing record.

Data were analyzed on a quarterly basis, and then compiled for an annual figure at the end of the study. At the end of the study, all physicians in the 3 intervention groups (n=12) were surveyed about their acceptance of incorporating moderate or maximal intervention into their clinical practice. This study was approved by the Institutional Review Board.

The control group was unaware of the study and had no contact with study personnel until the study was completed. The 3 intervention groups were divided into minimal, moderate, and maximal intervention.

Minimal intervention. Primary care physicians received a list of 100 of their patients designated as high users with identifying information. General suggestions were given to primary care physicians on how they could monitor/modify high users’ behavior: make regular appointments, have the nurse call for follow-up after an emergency department visit or hospital admission.

Moderate intervention. Primary care physicians received the initial list and quarterly updates of patients on their lists who had an emergency department visit or inpatient admission or did not follow-up with them in the clinic within 2 weeks of the high-cost encounter.

Maximal intervention. Intervention in the maximal group was the same as for moderate intervention, except that patients who did not make a follow-up visit within 2 weeks were contacted by a case manager to determine barriers to access and to facilitate a follow-up visit with the primary care physician. Where appropriate, a follow-up visit was made with the primary care physician by the case manager.

Outcome measures

Emergency department visits and inpatient admissions were designated as high-cost encounters because of their potential for high use, accounting for a significant portion of non-surgical cost for HMO members, and a high likelihood of lack of follow-up after the encounter. Review of HMO financial data revealed these to be members’ highest (nonsurgical) costs. A calculated variable: A high-cost encounter was calculated by determining a binary outcome variable derived by aggregating emergency department and inpatient visits.

Data analysis

The study groups were compared by logistic regression. The 95% confidence intervals (CIs) accompanying the odds ratios (ORs) are the tests of significance. If the range of the CI includes the value 1, the difference between groups being compared is not statistically significant (α=.05).

Results

Table 2 shows the OR of a high-cost encounter (emergency department visit or inpatient admission) for each intervention group. The unit of measure for this table is patient-months.^7,8 All ORs are read from left to right. For example, the minimal intervention group is 2.19 times more likely to have an emergency department event than maximal group.

The risk of a high-cost encounter was significantly greater for the minimal intervention than for the moderate or maximal intervention groups. The moderate group had a statistically significant greater risk of a high-cost encounter than the maximal intervention group, but the observed magnitude of the risk was small and the lower limit of the CI is very close to 1. The clinical importance of this finding may be questioned in light of the cost effectiveness of the maximal intervention.

The probability of an emergency department visit was significantly reduced for minimal compared with moderate and maximal intervention. The risk for emergency department events was the same for the moderate and maximal intervention groups.

The minimal group was more likely to have an admission than both the moderate and maximal intervention groups. The maximal group was also less likely to have an admission than the moderate intervention group. The moderate intervention appears to be the most costeffective because of reductions achieved with minimal staff involvement.

TABLE 2
Odds ratio of high-cost encounter* for each intervention group

Physician acceptance

All physicians in the 3 intervention groups were surveyed after study completion. Ninety percent agreed with the statement “I will use the moderate intervention now that it is shown to reduce utilization.”

Maximal intervention was thought to be less useful because many patients contacted were under the care of specialists and had no intention of returning to the primary care physician for care. Most of these patients did not require the use of the care manager, so the primary care physicians considered this extra expense as unnecessary.

Discussion

Our results appear to support the contention that primary care physicians can use relatively simple methods to monitor and modify the highuse behavior of members of their managed care panels. By designating frequent users of medical services as “high risk” for future utilization, primary care physicians can track these patients in a proactive fashion using a real-time database system.

At least in this relatively large, vertically integrated, multispecialty health system, emergency department and inpatient admissions were significantly reduced using the database. The moderate intervention appeared to be relatively well accepted by the primary care physicians and able to be instituted within their practice without much difficulty.

If adopted by larger health care systems, this method should result in considerable savings. Other studies in different health care settings are needed before this method can be recommended on a wider basis.

With escalating health care costs, primary care physicians need a simple way to monitor and modify the highusing behavior of their managed care patients. Several studies have shown that <20% of a primary care physician’s patient load will use 90% of the expended resources each year.¹ Although many of these expenditures may be unavoidable due to acute injury or illness, many of these high-users are patients with chronic illnesses.

Most efforts to contain costs have focused on developing clinical care protocols for expensive illnesses (ie, coronary heart failure, diabetes)² to reduce the need for inpatient management. Also, health maintenance organizations (HMOs) have developed incentive plans for physicians who hold down costs by reducing use of high-cost services.³ Several studies have shown that when realtime databases are used and available for feedback to physicians, quality improves and cost is contained.^4,5

Other than descriptions of disease-focused case management, there is little information in the literature on methods primary care physicians can use themselves to monitor patients’ use patterns. Our recent study showed that physicians are often unaware of the activity of some of their highest-using patients and miss the opportunity to intervene.⁶

We conducted a randomized prospective trial comparing 3 different interventions that primary care physicians can use to monitor and modify their patients’ resource use patterns. The goal of this study was to find a relatively simple method that would be accepted by primary care physicians to lower high-cost encounters among their highest users of medical services.

Methods

Study sample

Sixteen primary care physicians—employed at least 5 years at 4 different satellite clinics of a large multispecialty clinic—were randomly divided into a 4-member control group and three 4-member intervention groups. Two-year retrospective financial data of each physician’s patient load were analyzed to determine which patients had been among the top 10% in resource use each of the last 2 years.

From the resulting group of 3200 patients, 100 patients of each primary care physician were chosen randomly to be followed for 1 year, along with their primary care physician in the 4-member groups. All 1600 cases were available for analysis, maintaining health plan enrollment throughout the study period. Fourteen patients died during the study period. Health plan financial data and clinic visit data were used. Table 1 shows physician and patient demographics.

TABLE 1
Physician and patient demographics

Study design

Patients’ health care use for the study period was tracked through the information system of the multispecialty clinic. It was confirmed by reviewing charge data from the patients’ HMO billing record.

Data were analyzed on a quarterly basis, and then compiled for an annual figure at the end of the study. At the end of the study, all physicians in the 3 intervention groups (n=12) were surveyed about their acceptance of incorporating moderate or maximal intervention into their clinical practice. This study was approved by the Institutional Review Board.

The control group was unaware of the study and had no contact with study personnel until the study was completed. The 3 intervention groups were divided into minimal, moderate, and maximal intervention.

Minimal intervention. Primary care physicians received a list of 100 of their patients designated as high users with identifying information. General suggestions were given to primary care physicians on how they could monitor/modify high users’ behavior: make regular appointments, have the nurse call for follow-up after an emergency department visit or hospital admission.

Moderate intervention. Primary care physicians received the initial list and quarterly updates of patients on their lists who had an emergency department visit or inpatient admission or did not follow-up with them in the clinic within 2 weeks of the high-cost encounter.

Maximal intervention. Intervention in the maximal group was the same as for moderate intervention, except that patients who did not make a follow-up visit within 2 weeks were contacted by a case manager to determine barriers to access and to facilitate a follow-up visit with the primary care physician. Where appropriate, a follow-up visit was made with the primary care physician by the case manager.

Outcome measures

Emergency department visits and inpatient admissions were designated as high-cost encounters because of their potential for high use, accounting for a significant portion of non-surgical cost for HMO members, and a high likelihood of lack of follow-up after the encounter. Review of HMO financial data revealed these to be members’ highest (nonsurgical) costs. A calculated variable: A high-cost encounter was calculated by determining a binary outcome variable derived by aggregating emergency department and inpatient visits.

Data analysis

The study groups were compared by logistic regression. The 95% confidence intervals (CIs) accompanying the odds ratios (ORs) are the tests of significance. If the range of the CI includes the value 1, the difference between groups being compared is not statistically significant (α=.05).

Results

Table 2 shows the OR of a high-cost encounter (emergency department visit or inpatient admission) for each intervention group. The unit of measure for this table is patient-months.^7,8 All ORs are read from left to right. For example, the minimal intervention group is 2.19 times more likely to have an emergency department event than maximal group.

The risk of a high-cost encounter was significantly greater for the minimal intervention than for the moderate or maximal intervention groups. The moderate group had a statistically significant greater risk of a high-cost encounter than the maximal intervention group, but the observed magnitude of the risk was small and the lower limit of the CI is very close to 1. The clinical importance of this finding may be questioned in light of the cost effectiveness of the maximal intervention.

The probability of an emergency department visit was significantly reduced for minimal compared with moderate and maximal intervention. The risk for emergency department events was the same for the moderate and maximal intervention groups.

The minimal group was more likely to have an admission than both the moderate and maximal intervention groups. The maximal group was also less likely to have an admission than the moderate intervention group. The moderate intervention appears to be the most costeffective because of reductions achieved with minimal staff involvement.

TABLE 2
Odds ratio of high-cost encounter* for each intervention group

Physician acceptance

All physicians in the 3 intervention groups were surveyed after study completion. Ninety percent agreed with the statement “I will use the moderate intervention now that it is shown to reduce utilization.”

Maximal intervention was thought to be less useful because many patients contacted were under the care of specialists and had no intention of returning to the primary care physician for care. Most of these patients did not require the use of the care manager, so the primary care physicians considered this extra expense as unnecessary.

Discussion

Our results appear to support the contention that primary care physicians can use relatively simple methods to monitor and modify the highuse behavior of members of their managed care panels. By designating frequent users of medical services as “high risk” for future utilization, primary care physicians can track these patients in a proactive fashion using a real-time database system.

At least in this relatively large, vertically integrated, multispecialty health system, emergency department and inpatient admissions were significantly reduced using the database. The moderate intervention appeared to be relatively well accepted by the primary care physicians and able to be instituted within their practice without much difficulty.

If adopted by larger health care systems, this method should result in considerable savings. Other studies in different health care settings are needed before this method can be recommended on a wider basis.

Adapalene (Differin®) is a naphthoic-acid derivative with retinoid activity that is effective in the treatment of mild to moderate acne vulgaris.1-4 Adapalene, in both gel and cream formulations, at the marketed and approved concentration of 0.1%, is better tolerated than most tretinoin formulations, including tretinoin microsphere gel 0.1% (Retin-A Micro®) and tretinoin cream 0.025% (Avita®).5-10 The cumulative irritancy assay (patch test) is designed to assess the irritation potential of topically applied materials. Irritation results obtained from this type of assay are due to direct damage to the epidermal cells, and no immunologic (allergic) mechanism is involved. Results of this standard assay are widely accepted to be indicators of irritation. This study compared the irritation potential of adapalene gel and solution with several retinoid and retinoidlike products containing either tazarotene or tretinoin.back to top

METHODS This cumulative irritancy study was conducted as a single-center, randomized, controlled, investigator/evaluator, double-blind, intraindividual comparison involving healthy subjects meeting specific inclusion-exclusion criteria. The cumulative irritancy assay, a 21-day patch test, was designed to assess the irritation potential of topically applied dermatologic materials under stressful conditions (ie, occlusion).11 A total of 42 subjects (6 males and 36 females) ranging in age from 22.9 to 74.8 years were enrolled and evaluated. All subjects received adapalene gel 0.1%, adapalene solution 0.1%, tazarotene gel 0.1%, tazarotene gel 0.05%, tretinoin microsphere gel 0.1%, tretinoin cream 0.025%, tretinoin gel 0.025%, and white petrolatum (negative control). Approximately 0.2 g of each of the 7 test products and negative control was applied to 8 sites on the upper area of the back according to a predefined randomization list. Application was made under occlusive conditions for 24 hours (4 times per week) and 72 hours (once weekly) for 3 weeks. At each study visit, skin reactions (erythema scores±other local reactions) were assessed by the same trained board-certified physician evaluator during the study, 15 to 30 minutes after removal of the product, using the grading scale for erythema (Table 1).

Statistical Methodology Sample Size, Design, and Randomization—A standard sample size for this type of cumulative irritancy clinical study is 25 subjects. To account for the multiplicity of comparisons, planned enrollment was estimated at 48 subjects. Enrollment was completed at 42 subjects, with the consent of the sponsor. On initiation, each of the 8 products was applied to one of the zones (Z1–Z8) according to the predefined randomization schedule. This randomization schedule was generated by the RANUNI routine of SAS using 8x8 Latin squares. Statistically Analyzed Variables—For evaluating the cutaneous tolerance, a cumulative irritancy index (CII) was calculated for each treatment and for each subject, as follows: CII=sum of irritation score/number of readings. The following conventions were applied for the CII calculation: baseline (day 1) score was excluded from the calculation. When the irritation reaction was rated 3 for any site, the product application was discontinued for the incriminated sites, and a score of 3 was assigned to the remaining readings (last observation carried forward). When a subject missed a scheduled visit, the scores of the sites from the next visit were assigned to the previously missed visit. Individual CII scores were averaged across subjects to obtain an MCII score for each treatment. MCII scores were submitted to an analysis of variance with effects for subject, zone, and formulation. To adjust for multiple comparisons, MCII score was compared, and formulations were classified using the Tukey multiple comparisons test performed at the 1% and 5% significance levels. According to MCII values, each test product could be classified into the irritation classes (Table 2).

results Of the 42 subjects enrolled, 38 subjects (90.5%) completed the study. Demographic data are presented in Table 3. Results are summarized in Table 4 and Figure 1. Figure 2 shows a clinical photograph of typical irritation observed during the study.

Adapalene (Differin®) is a naphthoic-acid derivative with retinoid activity that is effective in the treatment of mild to moderate acne vulgaris.1-4 Adapalene, in both gel and cream formulations, at the marketed and approved concentration of 0.1%, is better tolerated than most tretinoin formulations, including tretinoin microsphere gel 0.1% (Retin-A Micro®) and tretinoin cream 0.025% (Avita®).5-10 The cumulative irritancy assay (patch test) is designed to assess the irritation potential of topically applied materials. Irritation results obtained from this type of assay are due to direct damage to the epidermal cells, and no immunologic (allergic) mechanism is involved. Results of this standard assay are widely accepted to be indicators of irritation. This study compared the irritation potential of adapalene gel and solution with several retinoid and retinoidlike products containing either tazarotene or tretinoin.back to top

METHODS This cumulative irritancy study was conducted as a single-center, randomized, controlled, investigator/evaluator, double-blind, intraindividual comparison involving healthy subjects meeting specific inclusion-exclusion criteria. The cumulative irritancy assay, a 21-day patch test, was designed to assess the irritation potential of topically applied dermatologic materials under stressful conditions (ie, occlusion).11 A total of 42 subjects (6 males and 36 females) ranging in age from 22.9 to 74.8 years were enrolled and evaluated. All subjects received adapalene gel 0.1%, adapalene solution 0.1%, tazarotene gel 0.1%, tazarotene gel 0.05%, tretinoin microsphere gel 0.1%, tretinoin cream 0.025%, tretinoin gel 0.025%, and white petrolatum (negative control). Approximately 0.2 g of each of the 7 test products and negative control was applied to 8 sites on the upper area of the back according to a predefined randomization list. Application was made under occlusive conditions for 24 hours (4 times per week) and 72 hours (once weekly) for 3 weeks. At each study visit, skin reactions (erythema scores±other local reactions) were assessed by the same trained board-certified physician evaluator during the study, 15 to 30 minutes after removal of the product, using the grading scale for erythema (Table 1).

Statistical Methodology Sample Size, Design, and Randomization—A standard sample size for this type of cumulative irritancy clinical study is 25 subjects. To account for the multiplicity of comparisons, planned enrollment was estimated at 48 subjects. Enrollment was completed at 42 subjects, with the consent of the sponsor. On initiation, each of the 8 products was applied to one of the zones (Z1–Z8) according to the predefined randomization schedule. This randomization schedule was generated by the RANUNI routine of SAS using 8x8 Latin squares. Statistically Analyzed Variables—For evaluating the cutaneous tolerance, a cumulative irritancy index (CII) was calculated for each treatment and for each subject, as follows: CII=sum of irritation score/number of readings. The following conventions were applied for the CII calculation: baseline (day 1) score was excluded from the calculation. When the irritation reaction was rated 3 for any site, the product application was discontinued for the incriminated sites, and a score of 3 was assigned to the remaining readings (last observation carried forward). When a subject missed a scheduled visit, the scores of the sites from the next visit were assigned to the previously missed visit. Individual CII scores were averaged across subjects to obtain an MCII score for each treatment. MCII scores were submitted to an analysis of variance with effects for subject, zone, and formulation. To adjust for multiple comparisons, MCII score was compared, and formulations were classified using the Tukey multiple comparisons test performed at the 1% and 5% significance levels. According to MCII values, each test product could be classified into the irritation classes (Table 2).

results Of the 42 subjects enrolled, 38 subjects (90.5%) completed the study. Demographic data are presented in Table 3. Results are summarized in Table 4 and Figure 1. Figure 2 shows a clinical photograph of typical irritation observed during the study.

Adapalene (Differin®) is a naphthoic-acid derivative with retinoid activity that is effective in the treatment of mild to moderate acne vulgaris.1-4 Adapalene, in both gel and cream formulations, at the marketed and approved concentration of 0.1%, is better tolerated than most tretinoin formulations, including tretinoin microsphere gel 0.1% (Retin-A Micro®) and tretinoin cream 0.025% (Avita®).5-10 The cumulative irritancy assay (patch test) is designed to assess the irritation potential of topically applied materials. Irritation results obtained from this type of assay are due to direct damage to the epidermal cells, and no immunologic (allergic) mechanism is involved. Results of this standard assay are widely accepted to be indicators of irritation. This study compared the irritation potential of adapalene gel and solution with several retinoid and retinoidlike products containing either tazarotene or tretinoin.back to top

METHODS This cumulative irritancy study was conducted as a single-center, randomized, controlled, investigator/evaluator, double-blind, intraindividual comparison involving healthy subjects meeting specific inclusion-exclusion criteria. The cumulative irritancy assay, a 21-day patch test, was designed to assess the irritation potential of topically applied dermatologic materials under stressful conditions (ie, occlusion).11 A total of 42 subjects (6 males and 36 females) ranging in age from 22.9 to 74.8 years were enrolled and evaluated. All subjects received adapalene gel 0.1%, adapalene solution 0.1%, tazarotene gel 0.1%, tazarotene gel 0.05%, tretinoin microsphere gel 0.1%, tretinoin cream 0.025%, tretinoin gel 0.025%, and white petrolatum (negative control). Approximately 0.2 g of each of the 7 test products and negative control was applied to 8 sites on the upper area of the back according to a predefined randomization list. Application was made under occlusive conditions for 24 hours (4 times per week) and 72 hours (once weekly) for 3 weeks. At each study visit, skin reactions (erythema scores±other local reactions) were assessed by the same trained board-certified physician evaluator during the study, 15 to 30 minutes after removal of the product, using the grading scale for erythema (Table 1).

Statistical Methodology Sample Size, Design, and Randomization—A standard sample size for this type of cumulative irritancy clinical study is 25 subjects. To account for the multiplicity of comparisons, planned enrollment was estimated at 48 subjects. Enrollment was completed at 42 subjects, with the consent of the sponsor. On initiation, each of the 8 products was applied to one of the zones (Z1–Z8) according to the predefined randomization schedule. This randomization schedule was generated by the RANUNI routine of SAS using 8x8 Latin squares. Statistically Analyzed Variables—For evaluating the cutaneous tolerance, a cumulative irritancy index (CII) was calculated for each treatment and for each subject, as follows: CII=sum of irritation score/number of readings. The following conventions were applied for the CII calculation: baseline (day 1) score was excluded from the calculation. When the irritation reaction was rated 3 for any site, the product application was discontinued for the incriminated sites, and a score of 3 was assigned to the remaining readings (last observation carried forward). When a subject missed a scheduled visit, the scores of the sites from the next visit were assigned to the previously missed visit. Individual CII scores were averaged across subjects to obtain an MCII score for each treatment. MCII scores were submitted to an analysis of variance with effects for subject, zone, and formulation. To adjust for multiple comparisons, MCII score was compared, and formulations were classified using the Tukey multiple comparisons test performed at the 1% and 5% significance levels. According to MCII values, each test product could be classified into the irritation classes (Table 2).

results Of the 42 subjects enrolled, 38 subjects (90.5%) completed the study. Demographic data are presented in Table 3. Results are summarized in Table 4 and Figure 1. Figure 2 shows a clinical photograph of typical irritation observed during the study.

Cutaneous melasma is a relatively common dermatologic disease, occurring most commonly in Asian and Hispanic women of childbearing years.1-5 Exposure to solar UV radiation is the most important environmental factor in the pathogenesis of melasma.2,3 Therapy for melasma remains a challenge. Pharmacologic treatments are the mainstay.2,6,7 Hydroquinone, azelaic acid, tretinoin, and topical corticosteroids have been used as monotherapy7-11 or in various combinations.12-15 Kligman and Willis15 found that monotherapy with hydroquinone, tretinoin, or the topical corticosteroid dexamethasone did not produce substantial hypopigmentation within a 3-month treatment period. However, they did observe satisfactory results with a combination of tretinoin 0.1%, hydroquinone 5.0%, and dexamethasone 0.1% in a hydrophilic ointment.15 Furthermore, Kligman and Willis,15 as well as other researchers, have noted efficacy and safety benefits with use of hydroquinone, tretinoin, and various topical corticosteroids. In experimental and clinical studies, the use of tretinoin and other retinoids has been found to abrogate the epidermal atrophy that can occur with topical corticosteroids.16,17 This could be due to the ability of tretinoin and other retinoids to induce hyperplasia of epidermal cells and to induce dermal collagen synthesis.16,17 The objective of the 2 well-controlled trials featured in this article was to compare the efficacy and safety of the combination of hydroquinone, tretinoin, and the fluorinated topical corticosteroid fluocinolone acetonide, in a hydrophilic cream formulation, with 3 dual-combination products in the clearing of melasma. back to top

METHODS Study Design—The 2 pivotal trials used similar multicenter, randomized, investigator-blind, active-control, parallel-group protocols. Thirteen centers were involved in these trials. Both studies compared a triple-combination hydrophilic cream vehicle containing tretinoin 0.05%, hydroquinone 4.0%, and fluocinolone acetonide 0.01% (RA+HQ+FA) with the dual-combination products tretinoin plus hydroquinone (RA+HQ), tretinoin plus fluocinolone acetonide (RA+FA), and hydroquinone plus fluocinolone acetonide (HQ+FA). All products involved the same drug concentrations and vehicle. All formulations were used once daily at night. A total of 641 adult patients were randomized to the various treatment groups. Objective evaluation of melasma severity at baseline and at various points after treatment involved investigator assessment of global improvement from baseline using an 8-point scale (0=completely clear to 7=worse) at each follow-up visit. A baseline photograph was used for comparison. Patient Population—Patients enrolled in the study were predominantly white women (aged 21 to 75 years) with Fitzpatrick skin types I through IV. For enrollment into the study, all patients had to demonstrate a stable hyperpigmentation on the face for at least 3 months’ duration, macular lesions that were neither depressed nor atrophic, and melasma severity scores of at least 2 (ie, hyperpigmentation that was at least moderately darker than the surrounding normal skin). There were no significant differences in demographic parameters or skin phototypes among patients in each of the 4 treatment groups. The degree of hyperpigmentation in all patients was moderate to severe. Efficacy and Safety Analysis—The primary efficacy end point involved the investigators’ assessment of the proportion of intent-to-treat patients in each treatment group who achieved complete clearing at week 8. The secondary end point (secondary success) involved the proportion of intent-to-treat patients in each treatment group who achieved complete clearing (score=0) or near-complete clearing (ie, mild residual hyperpigmentation, score=1) by week 8 (Table 1).

RESULTS Efficacy—Significantly more of the patients treated with RA+HQ+FA (26.1%) experienced complete clearing compared with each of the dual-therapy groups at week 8 (9.5% for RA+HQ, 1.9% for RA+FA, and 2.5% for HQ+FA, P

Cutaneous melasma is a relatively common dermatologic disease, occurring most commonly in Asian and Hispanic women of childbearing years.1-5 Exposure to solar UV radiation is the most important environmental factor in the pathogenesis of melasma.2,3 Therapy for melasma remains a challenge. Pharmacologic treatments are the mainstay.2,6,7 Hydroquinone, azelaic acid, tretinoin, and topical corticosteroids have been used as monotherapy7-11 or in various combinations.12-15 Kligman and Willis15 found that monotherapy with hydroquinone, tretinoin, or the topical corticosteroid dexamethasone did not produce substantial hypopigmentation within a 3-month treatment period. However, they did observe satisfactory results with a combination of tretinoin 0.1%, hydroquinone 5.0%, and dexamethasone 0.1% in a hydrophilic ointment.15 Furthermore, Kligman and Willis,15 as well as other researchers, have noted efficacy and safety benefits with use of hydroquinone, tretinoin, and various topical corticosteroids. In experimental and clinical studies, the use of tretinoin and other retinoids has been found to abrogate the epidermal atrophy that can occur with topical corticosteroids.16,17 This could be due to the ability of tretinoin and other retinoids to induce hyperplasia of epidermal cells and to induce dermal collagen synthesis.16,17 The objective of the 2 well-controlled trials featured in this article was to compare the efficacy and safety of the combination of hydroquinone, tretinoin, and the fluorinated topical corticosteroid fluocinolone acetonide, in a hydrophilic cream formulation, with 3 dual-combination products in the clearing of melasma. back to top

METHODS Study Design—The 2 pivotal trials used similar multicenter, randomized, investigator-blind, active-control, parallel-group protocols. Thirteen centers were involved in these trials. Both studies compared a triple-combination hydrophilic cream vehicle containing tretinoin 0.05%, hydroquinone 4.0%, and fluocinolone acetonide 0.01% (RA+HQ+FA) with the dual-combination products tretinoin plus hydroquinone (RA+HQ), tretinoin plus fluocinolone acetonide (RA+FA), and hydroquinone plus fluocinolone acetonide (HQ+FA). All products involved the same drug concentrations and vehicle. All formulations were used once daily at night. A total of 641 adult patients were randomized to the various treatment groups. Objective evaluation of melasma severity at baseline and at various points after treatment involved investigator assessment of global improvement from baseline using an 8-point scale (0=completely clear to 7=worse) at each follow-up visit. A baseline photograph was used for comparison. Patient Population—Patients enrolled in the study were predominantly white women (aged 21 to 75 years) with Fitzpatrick skin types I through IV. For enrollment into the study, all patients had to demonstrate a stable hyperpigmentation on the face for at least 3 months’ duration, macular lesions that were neither depressed nor atrophic, and melasma severity scores of at least 2 (ie, hyperpigmentation that was at least moderately darker than the surrounding normal skin). There were no significant differences in demographic parameters or skin phototypes among patients in each of the 4 treatment groups. The degree of hyperpigmentation in all patients was moderate to severe. Efficacy and Safety Analysis—The primary efficacy end point involved the investigators’ assessment of the proportion of intent-to-treat patients in each treatment group who achieved complete clearing at week 8. The secondary end point (secondary success) involved the proportion of intent-to-treat patients in each treatment group who achieved complete clearing (score=0) or near-complete clearing (ie, mild residual hyperpigmentation, score=1) by week 8 (Table 1).

RESULTS Efficacy—Significantly more of the patients treated with RA+HQ+FA (26.1%) experienced complete clearing compared with each of the dual-therapy groups at week 8 (9.5% for RA+HQ, 1.9% for RA+FA, and 2.5% for HQ+FA, P

Cutaneous melasma is a relatively common dermatologic disease, occurring most commonly in Asian and Hispanic women of childbearing years.1-5 Exposure to solar UV radiation is the most important environmental factor in the pathogenesis of melasma.2,3 Therapy for melasma remains a challenge. Pharmacologic treatments are the mainstay.2,6,7 Hydroquinone, azelaic acid, tretinoin, and topical corticosteroids have been used as monotherapy7-11 or in various combinations.12-15 Kligman and Willis15 found that monotherapy with hydroquinone, tretinoin, or the topical corticosteroid dexamethasone did not produce substantial hypopigmentation within a 3-month treatment period. However, they did observe satisfactory results with a combination of tretinoin 0.1%, hydroquinone 5.0%, and dexamethasone 0.1% in a hydrophilic ointment.15 Furthermore, Kligman and Willis,15 as well as other researchers, have noted efficacy and safety benefits with use of hydroquinone, tretinoin, and various topical corticosteroids. In experimental and clinical studies, the use of tretinoin and other retinoids has been found to abrogate the epidermal atrophy that can occur with topical corticosteroids.16,17 This could be due to the ability of tretinoin and other retinoids to induce hyperplasia of epidermal cells and to induce dermal collagen synthesis.16,17 The objective of the 2 well-controlled trials featured in this article was to compare the efficacy and safety of the combination of hydroquinone, tretinoin, and the fluorinated topical corticosteroid fluocinolone acetonide, in a hydrophilic cream formulation, with 3 dual-combination products in the clearing of melasma. back to top

METHODS Study Design—The 2 pivotal trials used similar multicenter, randomized, investigator-blind, active-control, parallel-group protocols. Thirteen centers were involved in these trials. Both studies compared a triple-combination hydrophilic cream vehicle containing tretinoin 0.05%, hydroquinone 4.0%, and fluocinolone acetonide 0.01% (RA+HQ+FA) with the dual-combination products tretinoin plus hydroquinone (RA+HQ), tretinoin plus fluocinolone acetonide (RA+FA), and hydroquinone plus fluocinolone acetonide (HQ+FA). All products involved the same drug concentrations and vehicle. All formulations were used once daily at night. A total of 641 adult patients were randomized to the various treatment groups. Objective evaluation of melasma severity at baseline and at various points after treatment involved investigator assessment of global improvement from baseline using an 8-point scale (0=completely clear to 7=worse) at each follow-up visit. A baseline photograph was used for comparison. Patient Population—Patients enrolled in the study were predominantly white women (aged 21 to 75 years) with Fitzpatrick skin types I through IV. For enrollment into the study, all patients had to demonstrate a stable hyperpigmentation on the face for at least 3 months’ duration, macular lesions that were neither depressed nor atrophic, and melasma severity scores of at least 2 (ie, hyperpigmentation that was at least moderately darker than the surrounding normal skin). There were no significant differences in demographic parameters or skin phototypes among patients in each of the 4 treatment groups. The degree of hyperpigmentation in all patients was moderate to severe. Efficacy and Safety Analysis—The primary efficacy end point involved the investigators’ assessment of the proportion of intent-to-treat patients in each treatment group who achieved complete clearing at week 8. The secondary end point (secondary success) involved the proportion of intent-to-treat patients in each treatment group who achieved complete clearing (score=0) or near-complete clearing (ie, mild residual hyperpigmentation, score=1) by week 8 (Table 1).

RESULTS Efficacy—Significantly more of the patients treated with RA+HQ+FA (26.1%) experienced complete clearing compared with each of the dual-therapy groups at week 8 (9.5% for RA+HQ, 1.9% for RA+FA, and 2.5% for HQ+FA, P

As the physician workforce diversifies,^1,2 the question of patients’ preferences for physicians by sex and race becomes increasingly important. Early investigations suggested that many patients, especially males, prefer same-sex physicians across a variety of clinical complaints,^3-5 but subsequent studies found these preferences to be more limited,^6-9 except for sex-specific health problems (eg, gynecologic examinations and sexual health issues).¹⁰

A more recent study examining patients’ actual selections of physicians in a large health maintenance organization showed that most patients of both sexes chose a male physician.¹¹ Whether these findings reflect actual patients’ preferences is debatable, however, because patients’ choices may have been influenced by the greater availability of male physicians on the panel.

Compared with sex, even less is known about preferences for physicians’ race, a topic that is complicated by patient and physician attributes such as language, religion, ethnicity, immigration status, acculturation, and multiracial identities. One recent survey on minority health care found that approximately one fourth of African American and Latino patients who had chosen same-race physicians reported explicitly considering the physician’s race or ethnicity in making their selection.¹²

In this study, we examined people’s choices when asked to select a male or female African American, Latino, or European American actor-portrayed “video doctor” to be their physician. Choices were examined at 2 time points: after viewing a brief introduction and after viewing the delivery of a brief health advice message. Our research questions were: After gaining a first impression, will patients choose a male of European descent regardless of their own sex and race? Will exposure to the video doctors’ deliveries of a brief health advice message alter these preferences? The video doctor methodology allowed us to offer participants a verisimilar experience of choosing a physician from a diverse panel and to avoid the limitations of availability and access inherent in real-life choices.

Methods

Video doctor filming and editing

We selected 6 actors of similar age (45 years) and attractiveness: 1 female and 1 male African American, Latino, and European American. We used the term Latino to represent a racial identity characterized by dark hair and a medium complexion. The fictitious surnames of the Latino and Latina video doctors also indicated their ethnicity.

When producing the video doctor presentations, we held constant the script, the setting (a doctor’s office), and the clothing. Two segments were produced for each video doctor: a brief introduction in which the doctor used a fictitious name assigned by the researchers to say, for example, “Hi, I’m Dr. Ann Johnson,” and a 45-second health advice message about eating 5 fruits and/or vegetables a day (chosen because of the neutral and universally relevant nature of this topic). The health message contained key elements known to enhance effectiveness of brief interventions.¹³ The actors’ deliveries of the message were standardized to include interpersonal elements associated with patient-centered health care and positive patient behavior change—for example, warmth, friendliness, empathy, and a nonjudgmental, respectful, and collaborative affect.^14,15 (A full description of our procedures is available in Appendix A at www.jfponline.com.)

To balance the video doctors with respect to any possible order effect, we created 18 video presentations showing the video doctors in different orders. We obtained the sequences by creating 6 x 6 Latin squares containing all 720 possible orders and then randomly selecting 3 Latin squares and using the 18 orders contained therein. By delivering 1 of the 18 orders to each group of 22 to 24 participants, we obtained nearly perfect balance in the ordering of the video doctors.

Participants

Individuals at a shopping mall in the San Francisco Bay Area aged >18 years and able to read and write English were invited to watch a short video and rate doctors for a healthcare research project. Four hundred people participated; 395 completed questionnaires. Participants were told that their responses were anonymous, and each questionnaire was marked only with the group number. Study procedures were approved by the Committee on Human Research at the University of California at San Francisco.

FIGURE
Video doctors

Study design and procedures

After viewing brief introductions of each video doctor (Figure), participants were asked: “If you were to choose 1 of these doctors to be your doctor, which would you pick?” They were then instructed to write the number of their choice on the questionnaire.

Participants then viewed the message from each video doctor about eating 5 fruits and vegetables a day. After each presentation, participants rated the video doctor by circling a number on 7-point scales, where a response of 7 indicated the following qualities: very professional, very knowledgeable, excellent communication skills, respectfulness, genuine/authentic, warm/friendly, and pleasant facial expressions.^14,15 Participants also rated each video doctor on a 7-point scale for how likely they would be to increase their fruit and vegetable consumption, how interested they might be in choosing this person as their doctor, and how comfortable they might be in talking with this person about personal health matters such as sexual, alcohol, and drug-using behaviors.

After viewing and rating all 6 video doctors, participants again viewed the 6 head shots together and answered the following question: “Now that you’ve heard each video doctor, which one would you pick to be your doctor?” To conclude, participants answered demographic questions, turned in their booklets, and received a $20 gift certificate.

Statistical analysis

Differences in the initial preferences for the sex and race of the video doctors by the sex and race of the participants were studied by using standard 2-way tables, with Fisher exact tests for 2 × 2 tables and χ² tests for larger tables. Multivariable analysis of sex preferences for the video doctor was done with logistic regression to test the effect of participants’ demographic variables. Matched pair analysis, with an exact version of the McNemar test, was used to assess whether participants’ tendency to choose a same-sex or a same-race video doctor changed from their initial to their final selection.

From each participant’s ratings of the video doctors, an assessment score was generated by averaging the 10 scaled ratings. The clustered assessment scores were analyzed with a normal linear mixed model analysis with a random effect to represent participant scoring tendency and fixed effects to account for the differential mean score for the preferred vs nonpreferred video doctors and differences in mean score depending on the order in which the video doctor was scored. All analyses were performed in Stata 6.0. (More detailed on the methods is found in Appendix A at www.jfponline.com.)

Results

Demographics

Participants were diverse in sex (61% female, 39% male), ethnicity (30% Asian American, 29% European American, 26% Latino, 8% African American, and 7% other), age (11% were 18 to 19 years old, 24% were 20 to 29, 18% were 30 to 39, 17% were 40 to 49, 13% were 50 to 59, 8% were 60 to 69, and 9% were 70 to 87), and education (9% had less than a high school education, 34% had a high school diploma or graduation equivalency diploma, 26% had some college, 22% were college graduates, and 9% had graduate degrees).

Initial preferences for video doctors

Initial sex preference. The strong preference for a female video doctor was significantly different from the 50% preference for each sex that would be expected in the absence of any sex preference (P<.0001). Most females (85%) and males (63%) selected a female video doctor (difference between males and females significant at P<.001; Table 1). The percentages of sex preference by race were not significantly different from one another (P=.36).

Multivariable logistic regression confirmed the relation between participants’ sex and the sex preference of the video doctor but showed no convincing evidence of differences in sex preference related to race (P=.73), age (P=.15), schooling (P=.23), marital status (P=.13), or employment status (P=.19).

Initial race preference. For their initial video doctor selection, 53% of participants chose a European American, 29% chose a Latino, and 18% chose an African American. This pattern of preference was significantly different from the 33.3% for each race that would be expected in the absence of a racial preference (P<.001; Table 2).

Video doctor racial preferences differed significantly by race of the participant (P<.0001), with a preference for the same race. A substantial number of participants, however, chose a different-race video doctor. Racial preferences were similar across male and female participants (P=.98).

TABLE 1
Initial and final video doctor selections by sex

TABLE 2
Initial and final video doctor selections by race

Final preferences for video doctors

Final sex preference. The preference for a female video doctor increased across female and male participants (P<.001; Table 1). The net shift among males from male to female video doctor was significant (P=.014). More female participants shifted from male to female (9%) than from female to male (4%), although the difference was not statistically significant (P=.10).

Final race preference. Forty-eight percent of African American participants, 56% of Latino participants, and 44% of European Americans chose a different-race video doctor. Among Asian and other-race participants, a sizable shift occurred so that only 43% selected a European American video doctor (Table 2).

Between the initial and final selections, 3% of African American participants shifted to a video doctor of a different race, whereas 7% shifted to an African American video doctor. Eleven percent of Latino participants shifted to a different-race video doctor, whereas 6% shifted to a Latino video doctor. Among European American participants, 22% shifted to a different-race video doctor, whereas 12% shifted to a European American video doctor. With the exception of African American participants, there was a significant net shift from same- to different-race choice (P=.036). Many Asian and other-race participants shifted from a European American video doctor to a non–European American video doctor (14% net).

Assessment scores

The 3 female video doctors, who were chosen by more participants than were the 3 male video doctors at the initial and final selections, also received higher mean assessment scores (Table 3). On particular items, the highest score was 6.001 (of a possible 7), received by the European American female for the question: “How professional is this doctor?” The lowest score was 3.590 received by the European American male for the question: “If this person were your doctor, how comfortable might you be in talking with this person about personal health matters?”

TABLE 3
Selection of video doctor by sex and race

Association of preferences and ratings. Analysis of the mean assessment scores showed a substantial rating tendency among participants, by which they tended to give all 6 video doctors relatively high or low scores. Our analysis indicated that 34.9% (95% confidence interval [CI], 30.4–39.5) of the variance in assessment scores is explained by rating tendency.

We also found that participants tended to increase their scores as they proceeded through the sequence of doctors. Compared with the first video doctor, the second through the sixth video doctors received increases in mean scores of 0.15 (P=.016), 0.16 (P=.011), 0.29 (P<.001), 0.43 (P<.001), and 0.60 (P<.001), respectively. These results showed the importance of using multiple presentation orders to balance the order effect.

After adjusting for the order effect and the respondent rating tendency, the mean assessment scores given to video doctors selected at the initial stage were an average of 0.7 points higher than scores given to the other video doctors (P<.001, 95% CI, 0.56–0.81). At the final selection, the chosen video doctor scored on average 1.04 units higher on the assessment scores than did the other video doctors (P<.001, 95% CI, 0.94–1.1). Thus, the selection made based on the video doctors’ images and brief introductions alone was significantly associated with the subsequent assessment, and the final selection of video doctor was even more strongly associated with the assessment.

Discussion

More participants preferred same-race physicians at the initial selection (66% of European Americans, 51% of Latinos, and 50% of African Americans). This effect was not as large as one might expect, however, because a substantial minority of subjects in each racial category selected a different-race video doctor at the initial selection and a majority of Latinos selected a different-race video doctor at the final selection.

After viewing the delivery of the prevention message, more in each group, except for African Americans, chose a video doctor of a different race. In addition, at final selection, 57% of Asian and other-race participants chose a non– European American video doctor. With regard to sex, most males and females chose a female video doctor at the initial selection, and even more did so at the final selection. These data suggested that many healthcare consumers are in concordance with the recent shift toward a more diverse population of physicians and that the white male physician may no longer be viewed as the stereotypical medical professional.

The qualities patients seek in a doctor

The assessment scores for the video doctors indicated that participants were choosing, both on first impressions and after further exposure, video doctors who they perceived to possess the qualities associated with patient-centered care.^21,22 Although the overall ranking of the 6 video doctors was unchanged from initial to final selection, after viewing the delivery of the prevention message, many participants altered their choices: more males and females chose a female video doctor; more European American and Latino participants shifted from same-race to different-race video doctors; and more Asian and other-race participants shifted from European American to non–European American video doctors.

These findings suggested that, even in brief meetings with physicians, patients respond to a combination of patient-centered qualities and that this combination may carry more weight than the physician’s sex and race. In other words, from the point of view of the public at large, physicians of both sexes and all races can possess the desired physician qualities, and people may be receptive to any physician who exhibits these qualities.

Preference for a female doctor

Our finding that men and women in our sample preferred a female video doctor contrasts with sex preference findings from previous studies,^3,6,8,10,11 although in general studies on sex preference of physicians have shown inconsistent findings. The female preference finding in our study may represent evolving positive attitudes toward and increasing familiarity with female physicians. From 1971 to 1991, the percentage of women first-year medical school students rose from 13.7% to 39.8%.¹⁴

The strong female preference also may represent sex stereotyping. Patients reported that they desire physicians who are sensitive to their needs and circumstances, deliver a warm and empathic style of care,¹⁵ invite participation in decision making,¹⁶ engage in emotionally focused talk, and provide health information within patients’ social, emotional, and cultural contexts.¹⁷ Other studies found that women, when compared with men, provide a style of care that approximates these patient-centered characteristics.^18-20

Our participants, many of whom preferred female video doctors even at first, may have strongly associated a patient-centered, empathic style with being female. The particular female actors we chose also may have been better able to exhibit, regardless of our efforts to standardize, the combination of professional and personal skills most desired in a doctor.

Racial preferences

The preference for a same-race video doctor may have several origins. People may feel more familiar and comfortable with race-concordant relationships in general and may believe that a physician of one’s own race can better attend to specific health concerns. Same-race preference also may arise from the desire to avoid a racially prejudiced physician. Racially concordant as opposed to discordant care has been associated with increased patient satisfaction and use of health care services and with higher ratings from patients regarding their level of participation during physician visits.^16,23

As indicated in our study and others, African Americans express a stronger preference than do individuals from other racial groups for receiving care from physicians of their own race.²³ To support patients in exercising their racial preferences, some health care professional organizations, such as the National Medical Association, have provided a toll-free number that patients can call to locate a local African American physician.

Limitations of the study

The study had several limitations. We may not have successfully held constant the actors’ personalities and acting abilities. Future video doctor studies about patients’ acceptance regarding physicians’ race and sex could address this drawback by including multiple video doctors in each sex and race category.

Because only English-speaking participants were included in the study, we do not know whether Latinos who spoke only Spanish would have chosen differently. Our study also used a convenience sample in a San Francisco Bay Area shopping mall, and our results may not be generalizable to other populations.

We were unable to study the same-race preferences of the Asian participants in our sample. Because more than 10% of physicians practicing in the United States are of Asian ancestry, patients’ receptivity to Asian physicians and Asian patients’ preference for a same-race physician would be important research topics. Diversity of language and culture among various Asian and other ethnicities also could be addressed with a well-designed video doctor study. The absence of an Asian video doctor, however, did allow us to examine the selections made by participants when no same-race video doctor was available.

Strengths of the study

A major strength of our study was that participants represented both sexes and a range of ages, races, and education levels. In addition, the video technology allowed participants to select a video doctor based on a verisimilar experience and without the constraints of availability and access found in real-life choices. All our study participants accepted the survey questions and responded to the video doctor as a “real” physician.

Video doctor technology does allow for holding constant certain variables such as age, appearance, message content, and style of delivery, an advantage that cannot be achieved in real encounters between patients and physicians.

Challenges for the future

Some of our most crucial health care challenges are providing access to quality care and equal career opportunities for those who seek to practice medicine. Our results supported the growing diversity of the population of physicians, and emphasized that many patients will choose physicians, regardless of their sex and race, who appear professional, competent, and caring. Medical schools need to continue the trend toward teaching patient-centered, empathic care and recruiting and retaining minority physicians to rectify current imbalances. In addition, practicing physicians can take note that providing quality care for patients of all cultural backgrounds may be an easier task than they think—the common language of compassion may transcend our differences.

Future studies could use video doctor technology to confirm our findings and to further investigate patients’ preferences and attitudes about various dimensions of the relationship between patient and physician. As the patient population and the physician workforce diversify, and as managed care organizations continue to strive to increase patient satisfaction and retention, information about patient preferences could inform the future of health care delivery.

Acknowledgments

We thank Scott Ludwig for his excellent casting of actors, directing, and video production; and Annabelle Ison for designing subject recruitment materials. We also thank our video doctors, the staff of Tanforan Park Shopping Center in San Bruno, CA, and the mall visitors who volunteered to participate in the study.

Corresponding author
Barbara Gerbert, PhD, University of California at San Francisco, 350 Parnassus Avenue, Suite 905, San Francisco, CA 94117. E-mail: [email protected].

As the physician workforce diversifies,^1,2 the question of patients’ preferences for physicians by sex and race becomes increasingly important. Early investigations suggested that many patients, especially males, prefer same-sex physicians across a variety of clinical complaints,^3-5 but subsequent studies found these preferences to be more limited,^6-9 except for sex-specific health problems (eg, gynecologic examinations and sexual health issues).¹⁰

A more recent study examining patients’ actual selections of physicians in a large health maintenance organization showed that most patients of both sexes chose a male physician.¹¹ Whether these findings reflect actual patients’ preferences is debatable, however, because patients’ choices may have been influenced by the greater availability of male physicians on the panel.

Compared with sex, even less is known about preferences for physicians’ race, a topic that is complicated by patient and physician attributes such as language, religion, ethnicity, immigration status, acculturation, and multiracial identities. One recent survey on minority health care found that approximately one fourth of African American and Latino patients who had chosen same-race physicians reported explicitly considering the physician’s race or ethnicity in making their selection.¹²

In this study, we examined people’s choices when asked to select a male or female African American, Latino, or European American actor-portrayed “video doctor” to be their physician. Choices were examined at 2 time points: after viewing a brief introduction and after viewing the delivery of a brief health advice message. Our research questions were: After gaining a first impression, will patients choose a male of European descent regardless of their own sex and race? Will exposure to the video doctors’ deliveries of a brief health advice message alter these preferences? The video doctor methodology allowed us to offer participants a verisimilar experience of choosing a physician from a diverse panel and to avoid the limitations of availability and access inherent in real-life choices.

Methods

Video doctor filming and editing

We selected 6 actors of similar age (45 years) and attractiveness: 1 female and 1 male African American, Latino, and European American. We used the term Latino to represent a racial identity characterized by dark hair and a medium complexion. The fictitious surnames of the Latino and Latina video doctors also indicated their ethnicity.

When producing the video doctor presentations, we held constant the script, the setting (a doctor’s office), and the clothing. Two segments were produced for each video doctor: a brief introduction in which the doctor used a fictitious name assigned by the researchers to say, for example, “Hi, I’m Dr. Ann Johnson,” and a 45-second health advice message about eating 5 fruits and/or vegetables a day (chosen because of the neutral and universally relevant nature of this topic). The health message contained key elements known to enhance effectiveness of brief interventions.¹³ The actors’ deliveries of the message were standardized to include interpersonal elements associated with patient-centered health care and positive patient behavior change—for example, warmth, friendliness, empathy, and a nonjudgmental, respectful, and collaborative affect.^14,15 (A full description of our procedures is available in Appendix A at www.jfponline.com.)

To balance the video doctors with respect to any possible order effect, we created 18 video presentations showing the video doctors in different orders. We obtained the sequences by creating 6 x 6 Latin squares containing all 720 possible orders and then randomly selecting 3 Latin squares and using the 18 orders contained therein. By delivering 1 of the 18 orders to each group of 22 to 24 participants, we obtained nearly perfect balance in the ordering of the video doctors.

Participants

Individuals at a shopping mall in the San Francisco Bay Area aged >18 years and able to read and write English were invited to watch a short video and rate doctors for a healthcare research project. Four hundred people participated; 395 completed questionnaires. Participants were told that their responses were anonymous, and each questionnaire was marked only with the group number. Study procedures were approved by the Committee on Human Research at the University of California at San Francisco.

FIGURE
Video doctors

Study design and procedures

After viewing brief introductions of each video doctor (Figure), participants were asked: “If you were to choose 1 of these doctors to be your doctor, which would you pick?” They were then instructed to write the number of their choice on the questionnaire.

Participants then viewed the message from each video doctor about eating 5 fruits and vegetables a day. After each presentation, participants rated the video doctor by circling a number on 7-point scales, where a response of 7 indicated the following qualities: very professional, very knowledgeable, excellent communication skills, respectfulness, genuine/authentic, warm/friendly, and pleasant facial expressions.^14,15 Participants also rated each video doctor on a 7-point scale for how likely they would be to increase their fruit and vegetable consumption, how interested they might be in choosing this person as their doctor, and how comfortable they might be in talking with this person about personal health matters such as sexual, alcohol, and drug-using behaviors.

After viewing and rating all 6 video doctors, participants again viewed the 6 head shots together and answered the following question: “Now that you’ve heard each video doctor, which one would you pick to be your doctor?” To conclude, participants answered demographic questions, turned in their booklets, and received a $20 gift certificate.

Statistical analysis

Differences in the initial preferences for the sex and race of the video doctors by the sex and race of the participants were studied by using standard 2-way tables, with Fisher exact tests for 2 × 2 tables and χ² tests for larger tables. Multivariable analysis of sex preferences for the video doctor was done with logistic regression to test the effect of participants’ demographic variables. Matched pair analysis, with an exact version of the McNemar test, was used to assess whether participants’ tendency to choose a same-sex or a same-race video doctor changed from their initial to their final selection.

From each participant’s ratings of the video doctors, an assessment score was generated by averaging the 10 scaled ratings. The clustered assessment scores were analyzed with a normal linear mixed model analysis with a random effect to represent participant scoring tendency and fixed effects to account for the differential mean score for the preferred vs nonpreferred video doctors and differences in mean score depending on the order in which the video doctor was scored. All analyses were performed in Stata 6.0. (More detailed on the methods is found in Appendix A at www.jfponline.com.)

Results

Demographics

Participants were diverse in sex (61% female, 39% male), ethnicity (30% Asian American, 29% European American, 26% Latino, 8% African American, and 7% other), age (11% were 18 to 19 years old, 24% were 20 to 29, 18% were 30 to 39, 17% were 40 to 49, 13% were 50 to 59, 8% were 60 to 69, and 9% were 70 to 87), and education (9% had less than a high school education, 34% had a high school diploma or graduation equivalency diploma, 26% had some college, 22% were college graduates, and 9% had graduate degrees).

Initial preferences for video doctors

Initial sex preference. The strong preference for a female video doctor was significantly different from the 50% preference for each sex that would be expected in the absence of any sex preference (P<.0001). Most females (85%) and males (63%) selected a female video doctor (difference between males and females significant at P<.001; Table 1). The percentages of sex preference by race were not significantly different from one another (P=.36).

Multivariable logistic regression confirmed the relation between participants’ sex and the sex preference of the video doctor but showed no convincing evidence of differences in sex preference related to race (P=.73), age (P=.15), schooling (P=.23), marital status (P=.13), or employment status (P=.19).

Initial race preference. For their initial video doctor selection, 53% of participants chose a European American, 29% chose a Latino, and 18% chose an African American. This pattern of preference was significantly different from the 33.3% for each race that would be expected in the absence of a racial preference (P<.001; Table 2).

Video doctor racial preferences differed significantly by race of the participant (P<.0001), with a preference for the same race. A substantial number of participants, however, chose a different-race video doctor. Racial preferences were similar across male and female participants (P=.98).

TABLE 1
Initial and final video doctor selections by sex

TABLE 2
Initial and final video doctor selections by race

Final preferences for video doctors

Final sex preference. The preference for a female video doctor increased across female and male participants (P<.001; Table 1). The net shift among males from male to female video doctor was significant (P=.014). More female participants shifted from male to female (9%) than from female to male (4%), although the difference was not statistically significant (P=.10).

Final race preference. Forty-eight percent of African American participants, 56% of Latino participants, and 44% of European Americans chose a different-race video doctor. Among Asian and other-race participants, a sizable shift occurred so that only 43% selected a European American video doctor (Table 2).

Between the initial and final selections, 3% of African American participants shifted to a video doctor of a different race, whereas 7% shifted to an African American video doctor. Eleven percent of Latino participants shifted to a different-race video doctor, whereas 6% shifted to a Latino video doctor. Among European American participants, 22% shifted to a different-race video doctor, whereas 12% shifted to a European American video doctor. With the exception of African American participants, there was a significant net shift from same- to different-race choice (P=.036). Many Asian and other-race participants shifted from a European American video doctor to a non–European American video doctor (14% net).

Assessment scores

The 3 female video doctors, who were chosen by more participants than were the 3 male video doctors at the initial and final selections, also received higher mean assessment scores (Table 3). On particular items, the highest score was 6.001 (of a possible 7), received by the European American female for the question: “How professional is this doctor?” The lowest score was 3.590 received by the European American male for the question: “If this person were your doctor, how comfortable might you be in talking with this person about personal health matters?”

TABLE 3
Selection of video doctor by sex and race

Association of preferences and ratings. Analysis of the mean assessment scores showed a substantial rating tendency among participants, by which they tended to give all 6 video doctors relatively high or low scores. Our analysis indicated that 34.9% (95% confidence interval [CI], 30.4–39.5) of the variance in assessment scores is explained by rating tendency.

We also found that participants tended to increase their scores as they proceeded through the sequence of doctors. Compared with the first video doctor, the second through the sixth video doctors received increases in mean scores of 0.15 (P=.016), 0.16 (P=.011), 0.29 (P<.001), 0.43 (P<.001), and 0.60 (P<.001), respectively. These results showed the importance of using multiple presentation orders to balance the order effect.

After adjusting for the order effect and the respondent rating tendency, the mean assessment scores given to video doctors selected at the initial stage were an average of 0.7 points higher than scores given to the other video doctors (P<.001, 95% CI, 0.56–0.81). At the final selection, the chosen video doctor scored on average 1.04 units higher on the assessment scores than did the other video doctors (P<.001, 95% CI, 0.94–1.1). Thus, the selection made based on the video doctors’ images and brief introductions alone was significantly associated with the subsequent assessment, and the final selection of video doctor was even more strongly associated with the assessment.

Discussion

More participants preferred same-race physicians at the initial selection (66% of European Americans, 51% of Latinos, and 50% of African Americans). This effect was not as large as one might expect, however, because a substantial minority of subjects in each racial category selected a different-race video doctor at the initial selection and a majority of Latinos selected a different-race video doctor at the final selection.

After viewing the delivery of the prevention message, more in each group, except for African Americans, chose a video doctor of a different race. In addition, at final selection, 57% of Asian and other-race participants chose a non– European American video doctor. With regard to sex, most males and females chose a female video doctor at the initial selection, and even more did so at the final selection. These data suggested that many healthcare consumers are in concordance with the recent shift toward a more diverse population of physicians and that the white male physician may no longer be viewed as the stereotypical medical professional.

The qualities patients seek in a doctor

The assessment scores for the video doctors indicated that participants were choosing, both on first impressions and after further exposure, video doctors who they perceived to possess the qualities associated with patient-centered care.^21,22 Although the overall ranking of the 6 video doctors was unchanged from initial to final selection, after viewing the delivery of the prevention message, many participants altered their choices: more males and females chose a female video doctor; more European American and Latino participants shifted from same-race to different-race video doctors; and more Asian and other-race participants shifted from European American to non–European American video doctors.

These findings suggested that, even in brief meetings with physicians, patients respond to a combination of patient-centered qualities and that this combination may carry more weight than the physician’s sex and race. In other words, from the point of view of the public at large, physicians of both sexes and all races can possess the desired physician qualities, and people may be receptive to any physician who exhibits these qualities.

Preference for a female doctor

Our finding that men and women in our sample preferred a female video doctor contrasts with sex preference findings from previous studies,^3,6,8,10,11 although in general studies on sex preference of physicians have shown inconsistent findings. The female preference finding in our study may represent evolving positive attitudes toward and increasing familiarity with female physicians. From 1971 to 1991, the percentage of women first-year medical school students rose from 13.7% to 39.8%.¹⁴

The strong female preference also may represent sex stereotyping. Patients reported that they desire physicians who are sensitive to their needs and circumstances, deliver a warm and empathic style of care,¹⁵ invite participation in decision making,¹⁶ engage in emotionally focused talk, and provide health information within patients’ social, emotional, and cultural contexts.¹⁷ Other studies found that women, when compared with men, provide a style of care that approximates these patient-centered characteristics.^18-20

Our participants, many of whom preferred female video doctors even at first, may have strongly associated a patient-centered, empathic style with being female. The particular female actors we chose also may have been better able to exhibit, regardless of our efforts to standardize, the combination of professional and personal skills most desired in a doctor.

Racial preferences

The preference for a same-race video doctor may have several origins. People may feel more familiar and comfortable with race-concordant relationships in general and may believe that a physician of one’s own race can better attend to specific health concerns. Same-race preference also may arise from the desire to avoid a racially prejudiced physician. Racially concordant as opposed to discordant care has been associated with increased patient satisfaction and use of health care services and with higher ratings from patients regarding their level of participation during physician visits.^16,23

As indicated in our study and others, African Americans express a stronger preference than do individuals from other racial groups for receiving care from physicians of their own race.²³ To support patients in exercising their racial preferences, some health care professional organizations, such as the National Medical Association, have provided a toll-free number that patients can call to locate a local African American physician.

Limitations of the study

The study had several limitations. We may not have successfully held constant the actors’ personalities and acting abilities. Future video doctor studies about patients’ acceptance regarding physicians’ race and sex could address this drawback by including multiple video doctors in each sex and race category.

Because only English-speaking participants were included in the study, we do not know whether Latinos who spoke only Spanish would have chosen differently. Our study also used a convenience sample in a San Francisco Bay Area shopping mall, and our results may not be generalizable to other populations.

We were unable to study the same-race preferences of the Asian participants in our sample. Because more than 10% of physicians practicing in the United States are of Asian ancestry, patients’ receptivity to Asian physicians and Asian patients’ preference for a same-race physician would be important research topics. Diversity of language and culture among various Asian and other ethnicities also could be addressed with a well-designed video doctor study. The absence of an Asian video doctor, however, did allow us to examine the selections made by participants when no same-race video doctor was available.

Strengths of the study

A major strength of our study was that participants represented both sexes and a range of ages, races, and education levels. In addition, the video technology allowed participants to select a video doctor based on a verisimilar experience and without the constraints of availability and access found in real-life choices. All our study participants accepted the survey questions and responded to the video doctor as a “real” physician.

Video doctor technology does allow for holding constant certain variables such as age, appearance, message content, and style of delivery, an advantage that cannot be achieved in real encounters between patients and physicians.

Challenges for the future

Some of our most crucial health care challenges are providing access to quality care and equal career opportunities for those who seek to practice medicine. Our results supported the growing diversity of the population of physicians, and emphasized that many patients will choose physicians, regardless of their sex and race, who appear professional, competent, and caring. Medical schools need to continue the trend toward teaching patient-centered, empathic care and recruiting and retaining minority physicians to rectify current imbalances. In addition, practicing physicians can take note that providing quality care for patients of all cultural backgrounds may be an easier task than they think—the common language of compassion may transcend our differences.

Future studies could use video doctor technology to confirm our findings and to further investigate patients’ preferences and attitudes about various dimensions of the relationship between patient and physician. As the patient population and the physician workforce diversify, and as managed care organizations continue to strive to increase patient satisfaction and retention, information about patient preferences could inform the future of health care delivery.

Acknowledgments

We thank Scott Ludwig for his excellent casting of actors, directing, and video production; and Annabelle Ison for designing subject recruitment materials. We also thank our video doctors, the staff of Tanforan Park Shopping Center in San Bruno, CA, and the mall visitors who volunteered to participate in the study.

Corresponding author
Barbara Gerbert, PhD, University of California at San Francisco, 350 Parnassus Avenue, Suite 905, San Francisco, CA 94117. E-mail: [email protected].

As the physician workforce diversifies,^1,2 the question of patients’ preferences for physicians by sex and race becomes increasingly important. Early investigations suggested that many patients, especially males, prefer same-sex physicians across a variety of clinical complaints,^3-5 but subsequent studies found these preferences to be more limited,^6-9 except for sex-specific health problems (eg, gynecologic examinations and sexual health issues).¹⁰

A more recent study examining patients’ actual selections of physicians in a large health maintenance organization showed that most patients of both sexes chose a male physician.¹¹ Whether these findings reflect actual patients’ preferences is debatable, however, because patients’ choices may have been influenced by the greater availability of male physicians on the panel.

Compared with sex, even less is known about preferences for physicians’ race, a topic that is complicated by patient and physician attributes such as language, religion, ethnicity, immigration status, acculturation, and multiracial identities. One recent survey on minority health care found that approximately one fourth of African American and Latino patients who had chosen same-race physicians reported explicitly considering the physician’s race or ethnicity in making their selection.¹²

In this study, we examined people’s choices when asked to select a male or female African American, Latino, or European American actor-portrayed “video doctor” to be their physician. Choices were examined at 2 time points: after viewing a brief introduction and after viewing the delivery of a brief health advice message. Our research questions were: After gaining a first impression, will patients choose a male of European descent regardless of their own sex and race? Will exposure to the video doctors’ deliveries of a brief health advice message alter these preferences? The video doctor methodology allowed us to offer participants a verisimilar experience of choosing a physician from a diverse panel and to avoid the limitations of availability and access inherent in real-life choices.

Methods

Video doctor filming and editing

We selected 6 actors of similar age (45 years) and attractiveness: 1 female and 1 male African American, Latino, and European American. We used the term Latino to represent a racial identity characterized by dark hair and a medium complexion. The fictitious surnames of the Latino and Latina video doctors also indicated their ethnicity.

When producing the video doctor presentations, we held constant the script, the setting (a doctor’s office), and the clothing. Two segments were produced for each video doctor: a brief introduction in which the doctor used a fictitious name assigned by the researchers to say, for example, “Hi, I’m Dr. Ann Johnson,” and a 45-second health advice message about eating 5 fruits and/or vegetables a day (chosen because of the neutral and universally relevant nature of this topic). The health message contained key elements known to enhance effectiveness of brief interventions.¹³ The actors’ deliveries of the message were standardized to include interpersonal elements associated with patient-centered health care and positive patient behavior change—for example, warmth, friendliness, empathy, and a nonjudgmental, respectful, and collaborative affect.^14,15 (A full description of our procedures is available in Appendix A at www.jfponline.com.)

To balance the video doctors with respect to any possible order effect, we created 18 video presentations showing the video doctors in different orders. We obtained the sequences by creating 6 x 6 Latin squares containing all 720 possible orders and then randomly selecting 3 Latin squares and using the 18 orders contained therein. By delivering 1 of the 18 orders to each group of 22 to 24 participants, we obtained nearly perfect balance in the ordering of the video doctors.

Participants

Individuals at a shopping mall in the San Francisco Bay Area aged >18 years and able to read and write English were invited to watch a short video and rate doctors for a healthcare research project. Four hundred people participated; 395 completed questionnaires. Participants were told that their responses were anonymous, and each questionnaire was marked only with the group number. Study procedures were approved by the Committee on Human Research at the University of California at San Francisco.

FIGURE
Video doctors

Study design and procedures

After viewing brief introductions of each video doctor (Figure), participants were asked: “If you were to choose 1 of these doctors to be your doctor, which would you pick?” They were then instructed to write the number of their choice on the questionnaire.

Participants then viewed the message from each video doctor about eating 5 fruits and vegetables a day. After each presentation, participants rated the video doctor by circling a number on 7-point scales, where a response of 7 indicated the following qualities: very professional, very knowledgeable, excellent communication skills, respectfulness, genuine/authentic, warm/friendly, and pleasant facial expressions.^14,15 Participants also rated each video doctor on a 7-point scale for how likely they would be to increase their fruit and vegetable consumption, how interested they might be in choosing this person as their doctor, and how comfortable they might be in talking with this person about personal health matters such as sexual, alcohol, and drug-using behaviors.

After viewing and rating all 6 video doctors, participants again viewed the 6 head shots together and answered the following question: “Now that you’ve heard each video doctor, which one would you pick to be your doctor?” To conclude, participants answered demographic questions, turned in their booklets, and received a $20 gift certificate.

Statistical analysis

Differences in the initial preferences for the sex and race of the video doctors by the sex and race of the participants were studied by using standard 2-way tables, with Fisher exact tests for 2 × 2 tables and χ² tests for larger tables. Multivariable analysis of sex preferences for the video doctor was done with logistic regression to test the effect of participants’ demographic variables. Matched pair analysis, with an exact version of the McNemar test, was used to assess whether participants’ tendency to choose a same-sex or a same-race video doctor changed from their initial to their final selection.

From each participant’s ratings of the video doctors, an assessment score was generated by averaging the 10 scaled ratings. The clustered assessment scores were analyzed with a normal linear mixed model analysis with a random effect to represent participant scoring tendency and fixed effects to account for the differential mean score for the preferred vs nonpreferred video doctors and differences in mean score depending on the order in which the video doctor was scored. All analyses were performed in Stata 6.0. (More detailed on the methods is found in Appendix A at www.jfponline.com.)

Results

Demographics

Participants were diverse in sex (61% female, 39% male), ethnicity (30% Asian American, 29% European American, 26% Latino, 8% African American, and 7% other), age (11% were 18 to 19 years old, 24% were 20 to 29, 18% were 30 to 39, 17% were 40 to 49, 13% were 50 to 59, 8% were 60 to 69, and 9% were 70 to 87), and education (9% had less than a high school education, 34% had a high school diploma or graduation equivalency diploma, 26% had some college, 22% were college graduates, and 9% had graduate degrees).

Initial preferences for video doctors

Initial sex preference. The strong preference for a female video doctor was significantly different from the 50% preference for each sex that would be expected in the absence of any sex preference (P<.0001). Most females (85%) and males (63%) selected a female video doctor (difference between males and females significant at P<.001; Table 1). The percentages of sex preference by race were not significantly different from one another (P=.36).

Multivariable logistic regression confirmed the relation between participants’ sex and the sex preference of the video doctor but showed no convincing evidence of differences in sex preference related to race (P=.73), age (P=.15), schooling (P=.23), marital status (P=.13), or employment status (P=.19).

Initial race preference. For their initial video doctor selection, 53% of participants chose a European American, 29% chose a Latino, and 18% chose an African American. This pattern of preference was significantly different from the 33.3% for each race that would be expected in the absence of a racial preference (P<.001; Table 2).

Video doctor racial preferences differed significantly by race of the participant (P<.0001), with a preference for the same race. A substantial number of participants, however, chose a different-race video doctor. Racial preferences were similar across male and female participants (P=.98).

TABLE 1
Initial and final video doctor selections by sex

TABLE 2
Initial and final video doctor selections by race

Final preferences for video doctors

Final sex preference. The preference for a female video doctor increased across female and male participants (P<.001; Table 1). The net shift among males from male to female video doctor was significant (P=.014). More female participants shifted from male to female (9%) than from female to male (4%), although the difference was not statistically significant (P=.10).

Final race preference. Forty-eight percent of African American participants, 56% of Latino participants, and 44% of European Americans chose a different-race video doctor. Among Asian and other-race participants, a sizable shift occurred so that only 43% selected a European American video doctor (Table 2).

Between the initial and final selections, 3% of African American participants shifted to a video doctor of a different race, whereas 7% shifted to an African American video doctor. Eleven percent of Latino participants shifted to a different-race video doctor, whereas 6% shifted to a Latino video doctor. Among European American participants, 22% shifted to a different-race video doctor, whereas 12% shifted to a European American video doctor. With the exception of African American participants, there was a significant net shift from same- to different-race choice (P=.036). Many Asian and other-race participants shifted from a European American video doctor to a non–European American video doctor (14% net).

Assessment scores

The 3 female video doctors, who were chosen by more participants than were the 3 male video doctors at the initial and final selections, also received higher mean assessment scores (Table 3). On particular items, the highest score was 6.001 (of a possible 7), received by the European American female for the question: “How professional is this doctor?” The lowest score was 3.590 received by the European American male for the question: “If this person were your doctor, how comfortable might you be in talking with this person about personal health matters?”

TABLE 3
Selection of video doctor by sex and race

Association of preferences and ratings. Analysis of the mean assessment scores showed a substantial rating tendency among participants, by which they tended to give all 6 video doctors relatively high or low scores. Our analysis indicated that 34.9% (95% confidence interval [CI], 30.4–39.5) of the variance in assessment scores is explained by rating tendency.

We also found that participants tended to increase their scores as they proceeded through the sequence of doctors. Compared with the first video doctor, the second through the sixth video doctors received increases in mean scores of 0.15 (P=.016), 0.16 (P=.011), 0.29 (P<.001), 0.43 (P<.001), and 0.60 (P<.001), respectively. These results showed the importance of using multiple presentation orders to balance the order effect.

After adjusting for the order effect and the respondent rating tendency, the mean assessment scores given to video doctors selected at the initial stage were an average of 0.7 points higher than scores given to the other video doctors (P<.001, 95% CI, 0.56–0.81). At the final selection, the chosen video doctor scored on average 1.04 units higher on the assessment scores than did the other video doctors (P<.001, 95% CI, 0.94–1.1). Thus, the selection made based on the video doctors’ images and brief introductions alone was significantly associated with the subsequent assessment, and the final selection of video doctor was even more strongly associated with the assessment.

Discussion

More participants preferred same-race physicians at the initial selection (66% of European Americans, 51% of Latinos, and 50% of African Americans). This effect was not as large as one might expect, however, because a substantial minority of subjects in each racial category selected a different-race video doctor at the initial selection and a majority of Latinos selected a different-race video doctor at the final selection.

After viewing the delivery of the prevention message, more in each group, except for African Americans, chose a video doctor of a different race. In addition, at final selection, 57% of Asian and other-race participants chose a non– European American video doctor. With regard to sex, most males and females chose a female video doctor at the initial selection, and even more did so at the final selection. These data suggested that many healthcare consumers are in concordance with the recent shift toward a more diverse population of physicians and that the white male physician may no longer be viewed as the stereotypical medical professional.

The qualities patients seek in a doctor

The assessment scores for the video doctors indicated that participants were choosing, both on first impressions and after further exposure, video doctors who they perceived to possess the qualities associated with patient-centered care.^21,22 Although the overall ranking of the 6 video doctors was unchanged from initial to final selection, after viewing the delivery of the prevention message, many participants altered their choices: more males and females chose a female video doctor; more European American and Latino participants shifted from same-race to different-race video doctors; and more Asian and other-race participants shifted from European American to non–European American video doctors.

These findings suggested that, even in brief meetings with physicians, patients respond to a combination of patient-centered qualities and that this combination may carry more weight than the physician’s sex and race. In other words, from the point of view of the public at large, physicians of both sexes and all races can possess the desired physician qualities, and people may be receptive to any physician who exhibits these qualities.

Preference for a female doctor

Our finding that men and women in our sample preferred a female video doctor contrasts with sex preference findings from previous studies,^3,6,8,10,11 although in general studies on sex preference of physicians have shown inconsistent findings. The female preference finding in our study may represent evolving positive attitudes toward and increasing familiarity with female physicians. From 1971 to 1991, the percentage of women first-year medical school students rose from 13.7% to 39.8%.¹⁴

The strong female preference also may represent sex stereotyping. Patients reported that they desire physicians who are sensitive to their needs and circumstances, deliver a warm and empathic style of care,¹⁵ invite participation in decision making,¹⁶ engage in emotionally focused talk, and provide health information within patients’ social, emotional, and cultural contexts.¹⁷ Other studies found that women, when compared with men, provide a style of care that approximates these patient-centered characteristics.^18-20

Our participants, many of whom preferred female video doctors even at first, may have strongly associated a patient-centered, empathic style with being female. The particular female actors we chose also may have been better able to exhibit, regardless of our efforts to standardize, the combination of professional and personal skills most desired in a doctor.

Racial preferences

The preference for a same-race video doctor may have several origins. People may feel more familiar and comfortable with race-concordant relationships in general and may believe that a physician of one’s own race can better attend to specific health concerns. Same-race preference also may arise from the desire to avoid a racially prejudiced physician. Racially concordant as opposed to discordant care has been associated with increased patient satisfaction and use of health care services and with higher ratings from patients regarding their level of participation during physician visits.^16,23

As indicated in our study and others, African Americans express a stronger preference than do individuals from other racial groups for receiving care from physicians of their own race.²³ To support patients in exercising their racial preferences, some health care professional organizations, such as the National Medical Association, have provided a toll-free number that patients can call to locate a local African American physician.

Limitations of the study

The study had several limitations. We may not have successfully held constant the actors’ personalities and acting abilities. Future video doctor studies about patients’ acceptance regarding physicians’ race and sex could address this drawback by including multiple video doctors in each sex and race category.

Because only English-speaking participants were included in the study, we do not know whether Latinos who spoke only Spanish would have chosen differently. Our study also used a convenience sample in a San Francisco Bay Area shopping mall, and our results may not be generalizable to other populations.

We were unable to study the same-race preferences of the Asian participants in our sample. Because more than 10% of physicians practicing in the United States are of Asian ancestry, patients’ receptivity to Asian physicians and Asian patients’ preference for a same-race physician would be important research topics. Diversity of language and culture among various Asian and other ethnicities also could be addressed with a well-designed video doctor study. The absence of an Asian video doctor, however, did allow us to examine the selections made by participants when no same-race video doctor was available.

Strengths of the study

A major strength of our study was that participants represented both sexes and a range of ages, races, and education levels. In addition, the video technology allowed participants to select a video doctor based on a verisimilar experience and without the constraints of availability and access found in real-life choices. All our study participants accepted the survey questions and responded to the video doctor as a “real” physician.

Video doctor technology does allow for holding constant certain variables such as age, appearance, message content, and style of delivery, an advantage that cannot be achieved in real encounters between patients and physicians.

Challenges for the future

Some of our most crucial health care challenges are providing access to quality care and equal career opportunities for those who seek to practice medicine. Our results supported the growing diversity of the population of physicians, and emphasized that many patients will choose physicians, regardless of their sex and race, who appear professional, competent, and caring. Medical schools need to continue the trend toward teaching patient-centered, empathic care and recruiting and retaining minority physicians to rectify current imbalances. In addition, practicing physicians can take note that providing quality care for patients of all cultural backgrounds may be an easier task than they think—the common language of compassion may transcend our differences.

Future studies could use video doctor technology to confirm our findings and to further investigate patients’ preferences and attitudes about various dimensions of the relationship between patient and physician. As the patient population and the physician workforce diversify, and as managed care organizations continue to strive to increase patient satisfaction and retention, information about patient preferences could inform the future of health care delivery.

Acknowledgments

We thank Scott Ludwig for his excellent casting of actors, directing, and video production; and Annabelle Ison for designing subject recruitment materials. We also thank our video doctors, the staff of Tanforan Park Shopping Center in San Bruno, CA, and the mall visitors who volunteered to participate in the study.

Corresponding author
Barbara Gerbert, PhD, University of California at San Francisco, 350 Parnassus Avenue, Suite 905, San Francisco, CA 94117. E-mail: [email protected].

Two recent surveys of patients undergoing cardiac surgery reported that 75% (263 of 376) and 81% (224 of 246) of patients currently use some form of complementary medicine (including herbs, vitamins, supplements, megavitamins, prayer, relaxation, spiritual healing, massage, imagery, and lifestyle and diet modifications).^1,2

Many herbal medicinal products are promoted for hypercholesterolemia, including some of the top-selling supplements. It is therefore vital to establish both the efficacy of these herbal supplements in reducing serum cholesterol levels and their relative safety. This review is an attempt to systematically summarize the evidence from randomized clinical trials for the efficacy and safety of lipid-lowering herbal medicinal products.

Methods

Identification of clinical trials

To identify clinical trials involving herbal medicinal products with hypocholesterolemic properties, we conducted systematic literature searches in the following electronic databases (all from their inception to May 2001): MEDLINE (via PubMed), EMBASE, CINAHL, AMED (Alternative and Allied Medicine Database, British Library Medical Information Centre), the Cochrane Library (Issue 2, 2001), and CISCOM (Research Council for Complementary Medicine, London, UK). The search strategy is summarized in Appendix A (available online at http://www.jfponline.com).

Further relevant papers were located by hand-searching the reference lists of all papers and departmental files. In addition, experts in the field and manufacturers were contacted to provide published and unpublished material.

Inclusion and exclusion criteria

Only randomized clinical trials investigating serum cholesterol reduction of monopreparations of herbal medicinal products administered as supplements were included. These could be placebo-controlled or equivalent trials. All retrieved data including uncontrolled trials, case reports, and preclinical and observational studies were reviewed for safety data. No language restrictions were imposed.

Data extraction and quality assessment

All articles were read in full. Data relating to sample size, study design, intervention and control, treatment duration, primary outcome measures, and results were extracted by the first author and validated by the second. The methodological quality of each trial was assessed using the Jadad scoring system,³ which ranges from 0 (poorest) to 5 (highest). A score of 3 or above indicates reasonable methodological quality.

Results

We identified 11 herbal medicinal products investigated for hypocholesterolemic properties in randomized clinical trials: guggul (Commiphora mukul), artichoke (Cynara scolymus), garlic (Allium sativum), fenugreek (Trigonella foenum- graecum), red yeast (Monascus purpureus) rice, Asian ginseng (Panax ginseng), yarrow (Achillea wilhelmsii), eggplant (Solanum melongena), holy basil (Ocimum sanctum), milk thistle (Silybum marianum), and arjun (Terminalia arjuna).

The efficacy and safety of garlic has been reviewed extensively elsewhere4–6 and is therefore not discussed in this paper. Details of all identified studies are shown in Tables 1–5 (and Table W1, available online at http://www.jfponline.com). Guggul, fenugreek, red yeast rice, and artichoke have been studied most extensively; randomized clinical trials of these herbal medicinal products with a Jadad score of 3 or above are discussed in more depth in Appendix B (available online at http://www.jfponline.com). Table 6 summarizes the adverse events experienced by subjects within these clinical trials and potential herb-drug interactions identified from systematic reviews.

Guggul (Commiphora mukul)

Six randomized clinical trials of guggul, involving 388 patients with different diagnoses, were identified.^7-12 Five were conducted in India and 1 in the United States; 4 were placebo-controlled; and 1 compared guggul with 2 reference compounds. The results suggest reductions in total serum cholesterol from 10% to 27% compared with baseline levels (Tables 1 and W1).

High-density lipoprotein (HDL) cholesterol levels were measured in 3 of the studies.^{7- 9} A significant increase was seen after 8 weeks of treatment in 1 study⁹; in the others, no significant differences were seen.^7,8 A statistically significant decrease in lipid peroxide levels was reported in 1 study, with no corresponding change in the placebo-treated group.⁷

Several mild adverse events were reported during these trials, including rash, nausea, vomiting, eructation, hiccup, headache, loose stools, restlessness, and apprehension, although information regarding adverse events experienced during placebo administration was not always provided. A potential drug interaction with propranolol and diltiazem was investigated in a randomized crossover trial of 17 healthy volunteers, in which guggul was found to significantly reduce the peak plasma concentration of both drugs.¹³

Fenugreek (Trigonella foenum-graecum)

Fenugreek seeds. Five randomized clinical trials were identified, involving 140 patients; all but 1 trial was conducted in India.^14-17 Although the methodological quality of the studies was considered generally poor in 4 of the trials, statistically significant reductions in total serum cholesterol of between 15% and 33% compared with baseline were demonstrated (Table 2).

Fenugreek leaves. In a single-blind study of 20 healthy male volunteers, Abdel-Barry and colleagues found a nonsignificant decrease of 9% in total serum cholesterol after a single dose of an aqueous extract made from fenugreek leaves (40 mg/kg) compared with a reduction of 2.8% after dilute coffee extract (placebo) (Table 2). ¹⁸

Within all the identified studies of fenugreek, patients reported mild gastrointestinal symptoms such as increased flatulence, nausea, fullness, and diarrhea during fenugreek treatment, but none was severe enough to necessitate withdrawal from the study. A 14% reduction in serum potassium was noted in healthy volunteers after a single dose of an aqueous extract of fenugreek leaves. ¹⁸

Red yeast rice

Red yeast rice is produced by solid-state fermentation of washed and cooked rice using the fungus Monascus purpureus. It has been used in Asia as a food preservative and colorant and for its medicinal properties since the Tang Dynasty (ad 800). It is available in capsules that contain a pulverized powder of fermented rice and yeast.

Four randomized clinical trials of the lipid-lowering effects of red yeast rice conducted in patients (n=695) with hyperlipidemia were identified (Table 3).^19-22 In all studies, statistically significant reductions (16% to 31%) in total serum cholesterol compared with placebo or control or baseline were seen.

Adverse events experienced in clinical trials included stomachache, heartburn, dizziness, and flatulence. No changes in liver function tests were demonstrated. There was 1 case report of a 26-year-old man who used red yeast rice in preparing sausages and developed anaphylaxis due to immediate sensitivity to M purpureus.²³ Whether this is relevant to the oral administration of red yeast rice capsules is not clear.

Artichoke (Cynara scolymus)

The choleretic effect of the leaf extract of artichoke has been studied widely, but only 2 randomized clinical trials of its hypocholesterolemic effects, involving 187 patients, were identified (Table 4).^24,25 One trial (n=44 healthy volunteers), published in abstract form only, found no significant difference in lipid levels compared with placebo, although post hoc subanalyses revealed some reductions in total serum cholesterol in patients with baseline levels above 5.4 mmol/L; these results should be interpreted with some caution. Reductions in total cholesterol of 18.5% and 8.6% were reported in the other, larger trial after artichoke and placebo treatments, respectively.

No adverse events were reported during either study. Three post-marketing surveillance studies were located: one included 417 patients and reported excellent tolerability in 95%; in the second (203 patients) no adverse reactions were reported; and the third (553 patients) described mild adverse events in 1.3% of patients (flatulence, hunger, and weakness).²⁴-²⁸

Discussion

Many different herbal medicinal products have been identified with potential lipid-lowering properties (Table 5), but the evidence for each herb is limited. The largest amount of published literature exists for guggul, fenugreek, red yeast rice, and artichoke, with reductions in total serum cholesterol ranging from 10% to 33%.

Although HDL and low-density lipoprotein (LDL) cholesterol were not measured in all the studies, increases in HDL and decreases in LDL levels were seen with guggul, red yeast rice, and yarrow, and decreases in LDL levels were seen in studies of fenugreek, arjun, and artichoke.

Safety

Few adverse events or drug interactions were reported in clinical trials of any of the 11 herbs identified. Many are used extensively in traditional medicine and culinary practices around the world, which supports their relative safety.

However, the long-term safety for use as herbal medicinal products has not been established. Long-term exposure of large numbers of patients within a formal setting would be necessary to determine safety, although difficulties associated with all herbal medicinal products exist, such as the inability to identify active ingredients and the potential for adulteration and misbranded products. No direct or indirect evidence exists for herb-drug interactions for fenugreek, guggul, Asian ginseng, and milk thistle (Table 6).

Study limitations

Although differences in study design, methodological quality, statistical methods, and subject populations create problems with interpretation of these figures, they appear to compare favorably with studies of garlic; the most recent meta-analysis suggested an average effect size of 4% to 6%.⁶ Studies of conventional therapeutic options for hypercholesterolemia (eg, statins) have demonstrated reductions of 20% to 30% in serum cholesterol.²⁹

Several shortcomings of the review need to be addressed. First, although attempts were made to obtain data from unpublished trials by contacting authors and manufacturers, none were located. There is evidence to suggest that studies with significant positive results are more likely to be published,³⁰ and this may be more pronounced with unfamiliar herbal therapies.

Second, because much of this research has been conducted in India and China, our extensive search strategy may not have located all the published material.

Third, there were several weaknesses with the original trials; of the 25 randomized clinical trials of herbal medicinal products for serum cholesterol reduction identified, only 12 scored 3 or more points on the Jadad scale. The most frequent methodological flaws were conduct of single-blind or open studies and incomplete reporting of methods of randomization, blinding, and subject withdrawals.

Conclusions

Evidence suggests that physicians do not ask their patients about complementary and alternative therapies and that patients are reticent to discuss these treatments with their physicians.^{31- 34} Surveys indicate widespread use of complementary and alternative therapies among patients undergoing cardiac surgery.^1,2 Although no equivalent surveys have been conducted for patients with hypercholesterolemia, in light of the relatively large number of herbal medicinal products with potential lipid-lowering properties available, it seems prudent for physicians to explore this area in their clinical decision-making process.

In conclusion, although 11 herbal medicinal products were identified with potential hypo-cholesterolemic activity, the evidence supporting individual plants is limited. In addition to lowering cholesterol, several of the herbs may exert beneficial effects in cardiovascular disease by elevating HDL levels and inhibiting lipid oxidation. The safety profiles of the products in question seems to be encouraging. Further research is therefore warranted to establish the therapeutic value of these herbs in the treatment of hypercholesterolemia.

Acknowledgments

The authors thank Jongbae Park, Barbara Wider, and Francesca Borelli, Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, for translation of papers from Chinese, Italian, and French, to and Esther Prati, Pharmaton, Lugano, for assistance with locating relevant articles. JTC received a research fellowship from Pharmaton SA, Lugano, Switzerland.

Two recent surveys of patients undergoing cardiac surgery reported that 75% (263 of 376) and 81% (224 of 246) of patients currently use some form of complementary medicine (including herbs, vitamins, supplements, megavitamins, prayer, relaxation, spiritual healing, massage, imagery, and lifestyle and diet modifications).^1,2

Many herbal medicinal products are promoted for hypercholesterolemia, including some of the top-selling supplements. It is therefore vital to establish both the efficacy of these herbal supplements in reducing serum cholesterol levels and their relative safety. This review is an attempt to systematically summarize the evidence from randomized clinical trials for the efficacy and safety of lipid-lowering herbal medicinal products.

Methods

Identification of clinical trials

To identify clinical trials involving herbal medicinal products with hypocholesterolemic properties, we conducted systematic literature searches in the following electronic databases (all from their inception to May 2001): MEDLINE (via PubMed), EMBASE, CINAHL, AMED (Alternative and Allied Medicine Database, British Library Medical Information Centre), the Cochrane Library (Issue 2, 2001), and CISCOM (Research Council for Complementary Medicine, London, UK). The search strategy is summarized in Appendix A (available online at http://www.jfponline.com).

Further relevant papers were located by hand-searching the reference lists of all papers and departmental files. In addition, experts in the field and manufacturers were contacted to provide published and unpublished material.

Inclusion and exclusion criteria

Only randomized clinical trials investigating serum cholesterol reduction of monopreparations of herbal medicinal products administered as supplements were included. These could be placebo-controlled or equivalent trials. All retrieved data including uncontrolled trials, case reports, and preclinical and observational studies were reviewed for safety data. No language restrictions were imposed.

Data extraction and quality assessment

All articles were read in full. Data relating to sample size, study design, intervention and control, treatment duration, primary outcome measures, and results were extracted by the first author and validated by the second. The methodological quality of each trial was assessed using the Jadad scoring system,³ which ranges from 0 (poorest) to 5 (highest). A score of 3 or above indicates reasonable methodological quality.

Results

We identified 11 herbal medicinal products investigated for hypocholesterolemic properties in randomized clinical trials: guggul (Commiphora mukul), artichoke (Cynara scolymus), garlic (Allium sativum), fenugreek (Trigonella foenum- graecum), red yeast (Monascus purpureus) rice, Asian ginseng (Panax ginseng), yarrow (Achillea wilhelmsii), eggplant (Solanum melongena), holy basil (Ocimum sanctum), milk thistle (Silybum marianum), and arjun (Terminalia arjuna).

The efficacy and safety of garlic has been reviewed extensively elsewhere4–6 and is therefore not discussed in this paper. Details of all identified studies are shown in Tables 1–5 (and Table W1, available online at http://www.jfponline.com). Guggul, fenugreek, red yeast rice, and artichoke have been studied most extensively; randomized clinical trials of these herbal medicinal products with a Jadad score of 3 or above are discussed in more depth in Appendix B (available online at http://www.jfponline.com). Table 6 summarizes the adverse events experienced by subjects within these clinical trials and potential herb-drug interactions identified from systematic reviews.

Guggul (Commiphora mukul)

Six randomized clinical trials of guggul, involving 388 patients with different diagnoses, were identified.^7-12 Five were conducted in India and 1 in the United States; 4 were placebo-controlled; and 1 compared guggul with 2 reference compounds. The results suggest reductions in total serum cholesterol from 10% to 27% compared with baseline levels (Tables 1 and W1).

High-density lipoprotein (HDL) cholesterol levels were measured in 3 of the studies.^{7- 9} A significant increase was seen after 8 weeks of treatment in 1 study⁹; in the others, no significant differences were seen.^7,8 A statistically significant decrease in lipid peroxide levels was reported in 1 study, with no corresponding change in the placebo-treated group.⁷

Several mild adverse events were reported during these trials, including rash, nausea, vomiting, eructation, hiccup, headache, loose stools, restlessness, and apprehension, although information regarding adverse events experienced during placebo administration was not always provided. A potential drug interaction with propranolol and diltiazem was investigated in a randomized crossover trial of 17 healthy volunteers, in which guggul was found to significantly reduce the peak plasma concentration of both drugs.¹³

Fenugreek (Trigonella foenum-graecum)

Fenugreek seeds. Five randomized clinical trials were identified, involving 140 patients; all but 1 trial was conducted in India.^14-17 Although the methodological quality of the studies was considered generally poor in 4 of the trials, statistically significant reductions in total serum cholesterol of between 15% and 33% compared with baseline were demonstrated (Table 2).

Fenugreek leaves. In a single-blind study of 20 healthy male volunteers, Abdel-Barry and colleagues found a nonsignificant decrease of 9% in total serum cholesterol after a single dose of an aqueous extract made from fenugreek leaves (40 mg/kg) compared with a reduction of 2.8% after dilute coffee extract (placebo) (Table 2). ¹⁸

Within all the identified studies of fenugreek, patients reported mild gastrointestinal symptoms such as increased flatulence, nausea, fullness, and diarrhea during fenugreek treatment, but none was severe enough to necessitate withdrawal from the study. A 14% reduction in serum potassium was noted in healthy volunteers after a single dose of an aqueous extract of fenugreek leaves. ¹⁸

Red yeast rice

Red yeast rice is produced by solid-state fermentation of washed and cooked rice using the fungus Monascus purpureus. It has been used in Asia as a food preservative and colorant and for its medicinal properties since the Tang Dynasty (ad 800). It is available in capsules that contain a pulverized powder of fermented rice and yeast.

Four randomized clinical trials of the lipid-lowering effects of red yeast rice conducted in patients (n=695) with hyperlipidemia were identified (Table 3).^19-22 In all studies, statistically significant reductions (16% to 31%) in total serum cholesterol compared with placebo or control or baseline were seen.

Adverse events experienced in clinical trials included stomachache, heartburn, dizziness, and flatulence. No changes in liver function tests were demonstrated. There was 1 case report of a 26-year-old man who used red yeast rice in preparing sausages and developed anaphylaxis due to immediate sensitivity to M purpureus.²³ Whether this is relevant to the oral administration of red yeast rice capsules is not clear.

Artichoke (Cynara scolymus)

The choleretic effect of the leaf extract of artichoke has been studied widely, but only 2 randomized clinical trials of its hypocholesterolemic effects, involving 187 patients, were identified (Table 4).^24,25 One trial (n=44 healthy volunteers), published in abstract form only, found no significant difference in lipid levels compared with placebo, although post hoc subanalyses revealed some reductions in total serum cholesterol in patients with baseline levels above 5.4 mmol/L; these results should be interpreted with some caution. Reductions in total cholesterol of 18.5% and 8.6% were reported in the other, larger trial after artichoke and placebo treatments, respectively.

No adverse events were reported during either study. Three post-marketing surveillance studies were located: one included 417 patients and reported excellent tolerability in 95%; in the second (203 patients) no adverse reactions were reported; and the third (553 patients) described mild adverse events in 1.3% of patients (flatulence, hunger, and weakness).²⁴-²⁸

Discussion

Many different herbal medicinal products have been identified with potential lipid-lowering properties (Table 5), but the evidence for each herb is limited. The largest amount of published literature exists for guggul, fenugreek, red yeast rice, and artichoke, with reductions in total serum cholesterol ranging from 10% to 33%.

Although HDL and low-density lipoprotein (LDL) cholesterol were not measured in all the studies, increases in HDL and decreases in LDL levels were seen with guggul, red yeast rice, and yarrow, and decreases in LDL levels were seen in studies of fenugreek, arjun, and artichoke.

Safety

Few adverse events or drug interactions were reported in clinical trials of any of the 11 herbs identified. Many are used extensively in traditional medicine and culinary practices around the world, which supports their relative safety.

However, the long-term safety for use as herbal medicinal products has not been established. Long-term exposure of large numbers of patients within a formal setting would be necessary to determine safety, although difficulties associated with all herbal medicinal products exist, such as the inability to identify active ingredients and the potential for adulteration and misbranded products. No direct or indirect evidence exists for herb-drug interactions for fenugreek, guggul, Asian ginseng, and milk thistle (Table 6).

Study limitations

Although differences in study design, methodological quality, statistical methods, and subject populations create problems with interpretation of these figures, they appear to compare favorably with studies of garlic; the most recent meta-analysis suggested an average effect size of 4% to 6%.⁶ Studies of conventional therapeutic options for hypercholesterolemia (eg, statins) have demonstrated reductions of 20% to 30% in serum cholesterol.²⁹

Several shortcomings of the review need to be addressed. First, although attempts were made to obtain data from unpublished trials by contacting authors and manufacturers, none were located. There is evidence to suggest that studies with significant positive results are more likely to be published,³⁰ and this may be more pronounced with unfamiliar herbal therapies.

Second, because much of this research has been conducted in India and China, our extensive search strategy may not have located all the published material.

Third, there were several weaknesses with the original trials; of the 25 randomized clinical trials of herbal medicinal products for serum cholesterol reduction identified, only 12 scored 3 or more points on the Jadad scale. The most frequent methodological flaws were conduct of single-blind or open studies and incomplete reporting of methods of randomization, blinding, and subject withdrawals.

Conclusions

Evidence suggests that physicians do not ask their patients about complementary and alternative therapies and that patients are reticent to discuss these treatments with their physicians.^{31- 34} Surveys indicate widespread use of complementary and alternative therapies among patients undergoing cardiac surgery.^1,2 Although no equivalent surveys have been conducted for patients with hypercholesterolemia, in light of the relatively large number of herbal medicinal products with potential lipid-lowering properties available, it seems prudent for physicians to explore this area in their clinical decision-making process.

In conclusion, although 11 herbal medicinal products were identified with potential hypo-cholesterolemic activity, the evidence supporting individual plants is limited. In addition to lowering cholesterol, several of the herbs may exert beneficial effects in cardiovascular disease by elevating HDL levels and inhibiting lipid oxidation. The safety profiles of the products in question seems to be encouraging. Further research is therefore warranted to establish the therapeutic value of these herbs in the treatment of hypercholesterolemia.

Acknowledgments

The authors thank Jongbae Park, Barbara Wider, and Francesca Borelli, Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, for translation of papers from Chinese, Italian, and French, to and Esther Prati, Pharmaton, Lugano, for assistance with locating relevant articles. JTC received a research fellowship from Pharmaton SA, Lugano, Switzerland.

Two recent surveys of patients undergoing cardiac surgery reported that 75% (263 of 376) and 81% (224 of 246) of patients currently use some form of complementary medicine (including herbs, vitamins, supplements, megavitamins, prayer, relaxation, spiritual healing, massage, imagery, and lifestyle and diet modifications).^1,2

Many herbal medicinal products are promoted for hypercholesterolemia, including some of the top-selling supplements. It is therefore vital to establish both the efficacy of these herbal supplements in reducing serum cholesterol levels and their relative safety. This review is an attempt to systematically summarize the evidence from randomized clinical trials for the efficacy and safety of lipid-lowering herbal medicinal products.

Methods

Identification of clinical trials

To identify clinical trials involving herbal medicinal products with hypocholesterolemic properties, we conducted systematic literature searches in the following electronic databases (all from their inception to May 2001): MEDLINE (via PubMed), EMBASE, CINAHL, AMED (Alternative and Allied Medicine Database, British Library Medical Information Centre), the Cochrane Library (Issue 2, 2001), and CISCOM (Research Council for Complementary Medicine, London, UK). The search strategy is summarized in Appendix A (available online at http://www.jfponline.com).

Further relevant papers were located by hand-searching the reference lists of all papers and departmental files. In addition, experts in the field and manufacturers were contacted to provide published and unpublished material.

Inclusion and exclusion criteria

Only randomized clinical trials investigating serum cholesterol reduction of monopreparations of herbal medicinal products administered as supplements were included. These could be placebo-controlled or equivalent trials. All retrieved data including uncontrolled trials, case reports, and preclinical and observational studies were reviewed for safety data. No language restrictions were imposed.

Data extraction and quality assessment

All articles were read in full. Data relating to sample size, study design, intervention and control, treatment duration, primary outcome measures, and results were extracted by the first author and validated by the second. The methodological quality of each trial was assessed using the Jadad scoring system,³ which ranges from 0 (poorest) to 5 (highest). A score of 3 or above indicates reasonable methodological quality.

Results

We identified 11 herbal medicinal products investigated for hypocholesterolemic properties in randomized clinical trials: guggul (Commiphora mukul), artichoke (Cynara scolymus), garlic (Allium sativum), fenugreek (Trigonella foenum- graecum), red yeast (Monascus purpureus) rice, Asian ginseng (Panax ginseng), yarrow (Achillea wilhelmsii), eggplant (Solanum melongena), holy basil (Ocimum sanctum), milk thistle (Silybum marianum), and arjun (Terminalia arjuna).

The efficacy and safety of garlic has been reviewed extensively elsewhere4–6 and is therefore not discussed in this paper. Details of all identified studies are shown in Tables 1–5 (and Table W1, available online at http://www.jfponline.com). Guggul, fenugreek, red yeast rice, and artichoke have been studied most extensively; randomized clinical trials of these herbal medicinal products with a Jadad score of 3 or above are discussed in more depth in Appendix B (available online at http://www.jfponline.com). Table 6 summarizes the adverse events experienced by subjects within these clinical trials and potential herb-drug interactions identified from systematic reviews.

Guggul (Commiphora mukul)

Six randomized clinical trials of guggul, involving 388 patients with different diagnoses, were identified.^7-12 Five were conducted in India and 1 in the United States; 4 were placebo-controlled; and 1 compared guggul with 2 reference compounds. The results suggest reductions in total serum cholesterol from 10% to 27% compared with baseline levels (Tables 1 and W1).

High-density lipoprotein (HDL) cholesterol levels were measured in 3 of the studies.^{7- 9} A significant increase was seen after 8 weeks of treatment in 1 study⁹; in the others, no significant differences were seen.^7,8 A statistically significant decrease in lipid peroxide levels was reported in 1 study, with no corresponding change in the placebo-treated group.⁷

Several mild adverse events were reported during these trials, including rash, nausea, vomiting, eructation, hiccup, headache, loose stools, restlessness, and apprehension, although information regarding adverse events experienced during placebo administration was not always provided. A potential drug interaction with propranolol and diltiazem was investigated in a randomized crossover trial of 17 healthy volunteers, in which guggul was found to significantly reduce the peak plasma concentration of both drugs.¹³

Fenugreek (Trigonella foenum-graecum)

Fenugreek seeds. Five randomized clinical trials were identified, involving 140 patients; all but 1 trial was conducted in India.^14-17 Although the methodological quality of the studies was considered generally poor in 4 of the trials, statistically significant reductions in total serum cholesterol of between 15% and 33% compared with baseline were demonstrated (Table 2).

Fenugreek leaves. In a single-blind study of 20 healthy male volunteers, Abdel-Barry and colleagues found a nonsignificant decrease of 9% in total serum cholesterol after a single dose of an aqueous extract made from fenugreek leaves (40 mg/kg) compared with a reduction of 2.8% after dilute coffee extract (placebo) (Table 2). ¹⁸

Within all the identified studies of fenugreek, patients reported mild gastrointestinal symptoms such as increased flatulence, nausea, fullness, and diarrhea during fenugreek treatment, but none was severe enough to necessitate withdrawal from the study. A 14% reduction in serum potassium was noted in healthy volunteers after a single dose of an aqueous extract of fenugreek leaves. ¹⁸

Red yeast rice

Red yeast rice is produced by solid-state fermentation of washed and cooked rice using the fungus Monascus purpureus. It has been used in Asia as a food preservative and colorant and for its medicinal properties since the Tang Dynasty (ad 800). It is available in capsules that contain a pulverized powder of fermented rice and yeast.

Four randomized clinical trials of the lipid-lowering effects of red yeast rice conducted in patients (n=695) with hyperlipidemia were identified (Table 3).^19-22 In all studies, statistically significant reductions (16% to 31%) in total serum cholesterol compared with placebo or control or baseline were seen.

Adverse events experienced in clinical trials included stomachache, heartburn, dizziness, and flatulence. No changes in liver function tests were demonstrated. There was 1 case report of a 26-year-old man who used red yeast rice in preparing sausages and developed anaphylaxis due to immediate sensitivity to M purpureus.²³ Whether this is relevant to the oral administration of red yeast rice capsules is not clear.

Artichoke (Cynara scolymus)

The choleretic effect of the leaf extract of artichoke has been studied widely, but only 2 randomized clinical trials of its hypocholesterolemic effects, involving 187 patients, were identified (Table 4).^24,25 One trial (n=44 healthy volunteers), published in abstract form only, found no significant difference in lipid levels compared with placebo, although post hoc subanalyses revealed some reductions in total serum cholesterol in patients with baseline levels above 5.4 mmol/L; these results should be interpreted with some caution. Reductions in total cholesterol of 18.5% and 8.6% were reported in the other, larger trial after artichoke and placebo treatments, respectively.

No adverse events were reported during either study. Three post-marketing surveillance studies were located: one included 417 patients and reported excellent tolerability in 95%; in the second (203 patients) no adverse reactions were reported; and the third (553 patients) described mild adverse events in 1.3% of patients (flatulence, hunger, and weakness).²⁴-²⁸

Discussion

Many different herbal medicinal products have been identified with potential lipid-lowering properties (Table 5), but the evidence for each herb is limited. The largest amount of published literature exists for guggul, fenugreek, red yeast rice, and artichoke, with reductions in total serum cholesterol ranging from 10% to 33%.

Although HDL and low-density lipoprotein (LDL) cholesterol were not measured in all the studies, increases in HDL and decreases in LDL levels were seen with guggul, red yeast rice, and yarrow, and decreases in LDL levels were seen in studies of fenugreek, arjun, and artichoke.

Safety

Few adverse events or drug interactions were reported in clinical trials of any of the 11 herbs identified. Many are used extensively in traditional medicine and culinary practices around the world, which supports their relative safety.

However, the long-term safety for use as herbal medicinal products has not been established. Long-term exposure of large numbers of patients within a formal setting would be necessary to determine safety, although difficulties associated with all herbal medicinal products exist, such as the inability to identify active ingredients and the potential for adulteration and misbranded products. No direct or indirect evidence exists for herb-drug interactions for fenugreek, guggul, Asian ginseng, and milk thistle (Table 6).

Study limitations

Although differences in study design, methodological quality, statistical methods, and subject populations create problems with interpretation of these figures, they appear to compare favorably with studies of garlic; the most recent meta-analysis suggested an average effect size of 4% to 6%.⁶ Studies of conventional therapeutic options for hypercholesterolemia (eg, statins) have demonstrated reductions of 20% to 30% in serum cholesterol.²⁹

Several shortcomings of the review need to be addressed. First, although attempts were made to obtain data from unpublished trials by contacting authors and manufacturers, none were located. There is evidence to suggest that studies with significant positive results are more likely to be published,³⁰ and this may be more pronounced with unfamiliar herbal therapies.

Second, because much of this research has been conducted in India and China, our extensive search strategy may not have located all the published material.

Third, there were several weaknesses with the original trials; of the 25 randomized clinical trials of herbal medicinal products for serum cholesterol reduction identified, only 12 scored 3 or more points on the Jadad scale. The most frequent methodological flaws were conduct of single-blind or open studies and incomplete reporting of methods of randomization, blinding, and subject withdrawals.

Conclusions

Evidence suggests that physicians do not ask their patients about complementary and alternative therapies and that patients are reticent to discuss these treatments with their physicians.^{31- 34} Surveys indicate widespread use of complementary and alternative therapies among patients undergoing cardiac surgery.^1,2 Although no equivalent surveys have been conducted for patients with hypercholesterolemia, in light of the relatively large number of herbal medicinal products with potential lipid-lowering properties available, it seems prudent for physicians to explore this area in their clinical decision-making process.

In conclusion, although 11 herbal medicinal products were identified with potential hypo-cholesterolemic activity, the evidence supporting individual plants is limited. In addition to lowering cholesterol, several of the herbs may exert beneficial effects in cardiovascular disease by elevating HDL levels and inhibiting lipid oxidation. The safety profiles of the products in question seems to be encouraging. Further research is therefore warranted to establish the therapeutic value of these herbs in the treatment of hypercholesterolemia.

Acknowledgments

The authors thank Jongbae Park, Barbara Wider, and Francesca Borelli, Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, for translation of papers from Chinese, Italian, and French, to and Esther Prati, Pharmaton, Lugano, for assistance with locating relevant articles. JTC received a research fellowship from Pharmaton SA, Lugano, Switzerland.