Participation and Successful Patient Recruitment in a Randomized Clinical Trial of Dyspepsia Treatment in Primary Care

Research in primary care is a growing field; the need for research on new diagnostic and therapeutic methods, the prognostic value of clinical signs and symptoms, and the effectiveness of clinical strategies in the population where these clinical contributions will be applied is well recognized.^1-5 The number and scale of research projects in primary care is expanding continuously, and research networks are being established.^6-8 This development, however, is putting increasing pressure on family physicians (FP) to actively participate in research. From an FP’s perspective there is a delicate balance between active research participation and efficient clinical practice.⁹ Proper planning to minimize paperwork and the delegation of research logistics to practice assistants can avoid many practical obstacles.^7,10,11

Motivating and recruiting FPs to participate is an essential step in conducting primary care research. Factors such as the clinical relevance of the research subject, personal interest in the topic, ownership, personal contact with the research group, and the required time investment have been shown to influence the participation of FPs.^5,11-15

Earlier studies have shown that higher-qualified physicians (with more continuing medical education training or a degree in research), physicians involved in under-or postgraduate training, FPs with research experience, and physicians working in well-organized practices (with more practice assistants and management protocols) are more interested in participating in research. Sex, the number of physicians per practice, and wages do not influence participation.¹⁵ The actual impact of financial incentives, however, is unclear. One study reported that incentives raised participation,¹⁶ while others could not confirm this.^12,15 Some have also drawn attention to the ethical and methodologic aspects of payment for research.^5,17

After successfully contracting with FPs to recruit patients for the study, the next task for a research group is to attain the maximal recruitment of patients. Unfortunately, less than half of the participating physicians actually recruit patients in the research project,^9,12,18 and often only a minority (20%)¹⁸ of the eligible patients are actually included. Our objective in this study was to identify practice and physician characteristics determining successful patient recruitment among FPs participating in a combined randomized clinical trial/cohort study on drug treatment of dyspepsia in the Netherlands.

Methods

Setting

Our data were compiled from a practice-based research network (PBRN) used for a primary care study of dyspepsia, the CIRANO study (Cisapride or Ranitidine in NonOrganic dyspepsia), which was conducted from 1996-1998 in the Netherlands. The CIRANO project consisted of 2 parts: a cohort study, in which dyspeptic patients were included and followed up for 1 year, and a randomized clinical trial in which patients selected from the cohort were treated with either an H2 blocker or a prokinetic drug.¹⁹ It was designed by the dyspepsia group of the Julius Centre, a group of primary care researchers who have been involved in gastrointestinal research and guideline development in the Netherlands for a number of years. Janssen Cilag Inc. was the sole sponsor of the project. The protocol was approved by the academic ethical committee, and data monitoring was done in accordance with the GCP guidelines (good clinical practice, a government protocol for conducting drug trials).

In the cohort study the workload for the participating physicians was small. After identification and inclusion by the FP, patients had to complete a validated dyspepsia symptom score, a quality of life questionnaire (COOP/WONCA chart), and a mental health state check list (GHQ 12). Also, the practice assistant performed a Helicobacter pylori whole- blood test. Follow-up of the patient was done by the research group. The FP workload in the clinical trial was heavier. After inclusion, the patients were randomized to one of the treatment arms, treated for 4 weeks, and followed up for 3 months. Patients were seen by the FP at inclusion and after 1 and 3 months.

Monitoring, data recording, and verification were performed by a clinical research organization under supervision of the research group. Data were stored and analyzed by the group.

FPs were given a financial incentive for each patient they included. It comprised a reimbursement for the extra practice time spent completing the research protocol. The estimated overall time investment for FPs was 2 hours with an additional 5 minutes for each patient included in the cohort and 1 additional hour for each patient included in the randomized clinical trial. Since the workload differed significantly, the reimbursement was higher for the patients included in the clinical trial ($25 per patient in the cohort, $70 for each patient in the randomized clinical trial). Also, project bulletins were distributed regularly during the course of the project.

All FPs in the academic network of the Utrecht University (2000 FPs, one third of all Dutch FPs) were invited by the academic research group to participate in the CIRANO study. Two hundred of them expressed interest in the study and asked for documentation. A total of 165 FPs finally signed the research contract.

Questionnaire

Five months after the CIRANO project was completed, all the participating physicians were sent an anonymous questionnaire containing 4 sections: (1) demographic and practice data, (2) initial motivation to participate, (3) evaluation of the logistics of the project, and (4) motivation to participate in future projects. The evaluation questions were Likert-type (a scale of 4 answer categories); motivation was analyzed by asking respondents to indicate the 3 most important reasons from a list of 8 Table 1. A reminder was sent 1 month after the first mailing. Data from the questionnaire, as well as the number of patients included in the study, were entered in SPSS for Windows software version 8.5 for analysis (SPSS, Inc; Chicago, Ill). Questionnaires that were not fully completed were excluded.

Analysis

To calculate odds ratios the number of recruited patients per FP was dichotomized, with cut-off points at the 25th percentile of inclusion: 0 to 4 versus 5 or more patients for inclusion in the cohort study, and 0 or 1 patient versus 2 or more for inclusion in the clinical trial. The association between demographic data, motivating factors and the number of recruited patients was calculated and expressed as an odds ratio (with 95% confidence interval [CI]). Factors that were thus associated with recruitment at a P level of less than 0.25 (so as not to exclude potentially important variables), together with 7 factors known from the literature to be relevant (sex, list size, years in practice, practice location, research experience, high specialization, and financial incentive-driven motivation) were entered in a logistic regression model.

Using a stepwise-backward procedure, determinants of maximal inclusion were analyzed and reported as adjusted odds ratio (with 95% CI). As the workload and the financial incentive for the clinical trial and cohort study differed significantly, we analyzed inclusion in the 2 parts of the research project separately.

Results

Of the 165 participating FPs, 132 returned the questionnaire; the response rate was 80%. Since 4 of the questionnaires were incomplete, data from 128 family physicians could be used for analysis. Most responders were men (87%), and half had been in practice for more than 5 years, primarily in semi-urban areas of the Netherlands (68%). Most (77%) were involved in other professional activities, such as vocational training, continuing medical education (CME), or activities of the College of Family Physicians (CFP) at the district level. Half the responders worked in a group practice, and more than 60% of the practices were “specialized” (defined as performing at least 4 of the following clinical activities in routine daily practice: minor surgery, Doppler studies, electrocardiography, cervical screening, intrauterine device insertion, diabetes protocol, or spirometry). Also, 57% of the participants had previous research experience.

The initial motivation for participation in the project varied Table 1. For the majority of the participants, the research topic and the participation of our academic research group were the most important factors. One third of the respondents considered participation a professional obligation, were attracted by the personal appeal by the research group, or were intrigued by the presentation of the project. The involvement of the sponsor and the financial incentive were important for only a minority in their decision to participate.

In general, the project was well evaluated; 80% of the respondents stated that the project had met their expectations (56% fully, 24% partially), and 60% noted that they would consider participation in a similar research project in the future. More specifically, the participants were satisfied with the quality of the correspondence, the newsletter, and the monitoring of the project Table 2. However, 47% of the participating FPs thought that the overall time investment in the project was too burdensome, and one third mentioned the negative impact the application of the GCP guidelines had on the workload of the project.

From September 1996 until January 1998 these 128 physicians recruited 793 patients in the cohort phase of the study (average = 6.3 per FP; standard deviation [SD]=6.6) and 527 in the clinical trial (average = 4.2 per FP; SD=4.9). A total of 15% of the FPs recruited no patients in the cohort study, while 59% recruited 4 or more patients. In comparison, 21% of the FPs did not recruit any patients in the clinical trial, and 65% recruited 2 or more patients.

In the univariate analysis only the factors “active in CME/CFP” and “motivation by the academic research group” were associated with the number of recruited patients. These associations occurred in both the cohort study and the randomized clinical trial Table 3. After entering these 2 factors were entered in a logistic model, together with 7 factors earlier reported relevant in the literature, multivariate analysis indicated that only the factor “motivation by the participation of the academic research group” predicted the number of patients recruited in cohort study (adjusted odds ratio [OR] = 3.5; 95% CI, 1.4-9.0) and clinical trial (adjusted OR = 2.9; 95% CI, 1.2-6.9).

Discussion

The combination of participation in research and daily clinical practice requires a major time investment. Even though FPs consider their participation thoroughly before a research project commences, the actual numbers of patients they recruit are often disappointing.

In this large randomized trial on dyspepsia in primary care we showed that those FPs whose motivation was driven by the participation of an academic department of family medicine in the research group recruited the most patients. They were 3 times more likely than their colleagues to recruit at least 2 patients for the clinical trial or 5 patients for the cohort. Other factors such as list (practice) size, involvement in professional CME/CFP activities, research experience, and financial incentive may have played a role in the FPs’ decision to participate in the research project but were not associated with the actual number of patients they recruited.

As in most projects, a minority of the participating physicians did not manage to recruit any patients. These colleagues either underestimated the time investment required, had second thoughts about the acceptability for their patients, or were disappointed by the planning and paperwork of the project.

Factors determining patient recruitment in primary care research have hardly been studied. Busy schedules, forgetfulness, poor patient compliance, and FP involvement in too many projects are a few of the reasons given to explain poor recruitment.^18,9

One third of all Dutch FPs were invited to participate in the dyspepsia study. Even though bias might have been caused by either the subject (dyspepsia physicians), the fact that half of the FPs had experience in research, or the fact that the participants were generally very active in numerous professional activities (active physicians), we think the results of our study can be generalized to the primary care setting in the Netherlands. Our conclusions may, however, require modification in other countries because of differences in practice organization and research climate in primary care.

Although there were various reasons for participation in the CIRANO study, they are consistent with earlier reports. FPs who participated in our dyspepsia project were mainly motivated by the subject and by the fact that the project was affiliated with our academic primary care research group. The motivation was not a matter of personal acquaintance, since most of the participants were not known to the members of the research group.

A substantial number of the participating colleagues also felt that participation was a professional obligation. This perception might have been induced by the fact that during the introduction of the project, special emphasis was put on the evidence missing from certain paragraphs of the Dutch guidelines on dyspepsia and on the need for primary care-based research to fill this gap. Although the research group felt that this was an important aspect of motivation, the evaluation showed that while it was an important reason to participate, it was not independently associated with patient recruitment. Only 10% of the participants stated that the financial incentive was a major reason to participate. Although this could be an unrealistic subjective statement, multivariate analysis confirmed that incentive-driven motivation was not related to the number of patients recruited. The fact that the results were the same for both the cohort study and the clinical trial might also be an indication that the amount of the incentive played a minor role in patient recruitment. This confirms earlier reports^12,13 that FPs probably do not participate in research for the money, although they do want a proper reimbursement for the time invested.

The fact that the majority of our study group were involved in professional education or organization confirms once again¹⁵ that active colleagues are the ones most motivated for research. Interest in research, however, obviously does not guarantee successful inclusion. Although a high level of practice organization and a high specialization in clinical activities have also reportedly been associated with optimal recruitment, we could not confirm this with our data.

Conclusions

Collaborators for primary care research projects should primarily be sought among the colleagues who are already active in different professional fields, and who have a strong affiliation with academic research. Successful participation is mainly determined by the initial motivation of the FP: Those who are motivated by the presence of an academic research group in the study recruit best. The research topic, the amount of the financial incentive, research experience, and other factors often suggested to influence patient recruitment are probably less important.

Research in primary care is a growing field; the need for research on new diagnostic and therapeutic methods, the prognostic value of clinical signs and symptoms, and the effectiveness of clinical strategies in the population where these clinical contributions will be applied is well recognized.^1-5 The number and scale of research projects in primary care is expanding continuously, and research networks are being established.^6-8 This development, however, is putting increasing pressure on family physicians (FP) to actively participate in research. From an FP’s perspective there is a delicate balance between active research participation and efficient clinical practice.⁹ Proper planning to minimize paperwork and the delegation of research logistics to practice assistants can avoid many practical obstacles.^7,10,11

Motivating and recruiting FPs to participate is an essential step in conducting primary care research. Factors such as the clinical relevance of the research subject, personal interest in the topic, ownership, personal contact with the research group, and the required time investment have been shown to influence the participation of FPs.^5,11-15

Earlier studies have shown that higher-qualified physicians (with more continuing medical education training or a degree in research), physicians involved in under-or postgraduate training, FPs with research experience, and physicians working in well-organized practices (with more practice assistants and management protocols) are more interested in participating in research. Sex, the number of physicians per practice, and wages do not influence participation.¹⁵ The actual impact of financial incentives, however, is unclear. One study reported that incentives raised participation,¹⁶ while others could not confirm this.^12,15 Some have also drawn attention to the ethical and methodologic aspects of payment for research.^5,17

After successfully contracting with FPs to recruit patients for the study, the next task for a research group is to attain the maximal recruitment of patients. Unfortunately, less than half of the participating physicians actually recruit patients in the research project,^9,12,18 and often only a minority (20%)¹⁸ of the eligible patients are actually included. Our objective in this study was to identify practice and physician characteristics determining successful patient recruitment among FPs participating in a combined randomized clinical trial/cohort study on drug treatment of dyspepsia in the Netherlands.

Methods

Setting

Our data were compiled from a practice-based research network (PBRN) used for a primary care study of dyspepsia, the CIRANO study (Cisapride or Ranitidine in NonOrganic dyspepsia), which was conducted from 1996-1998 in the Netherlands. The CIRANO project consisted of 2 parts: a cohort study, in which dyspeptic patients were included and followed up for 1 year, and a randomized clinical trial in which patients selected from the cohort were treated with either an H2 blocker or a prokinetic drug.¹⁹ It was designed by the dyspepsia group of the Julius Centre, a group of primary care researchers who have been involved in gastrointestinal research and guideline development in the Netherlands for a number of years. Janssen Cilag Inc. was the sole sponsor of the project. The protocol was approved by the academic ethical committee, and data monitoring was done in accordance with the GCP guidelines (good clinical practice, a government protocol for conducting drug trials).

In the cohort study the workload for the participating physicians was small. After identification and inclusion by the FP, patients had to complete a validated dyspepsia symptom score, a quality of life questionnaire (COOP/WONCA chart), and a mental health state check list (GHQ 12). Also, the practice assistant performed a Helicobacter pylori whole- blood test. Follow-up of the patient was done by the research group. The FP workload in the clinical trial was heavier. After inclusion, the patients were randomized to one of the treatment arms, treated for 4 weeks, and followed up for 3 months. Patients were seen by the FP at inclusion and after 1 and 3 months.

Monitoring, data recording, and verification were performed by a clinical research organization under supervision of the research group. Data were stored and analyzed by the group.

FPs were given a financial incentive for each patient they included. It comprised a reimbursement for the extra practice time spent completing the research protocol. The estimated overall time investment for FPs was 2 hours with an additional 5 minutes for each patient included in the cohort and 1 additional hour for each patient included in the randomized clinical trial. Since the workload differed significantly, the reimbursement was higher for the patients included in the clinical trial ($25 per patient in the cohort, $70 for each patient in the randomized clinical trial). Also, project bulletins were distributed regularly during the course of the project.

All FPs in the academic network of the Utrecht University (2000 FPs, one third of all Dutch FPs) were invited by the academic research group to participate in the CIRANO study. Two hundred of them expressed interest in the study and asked for documentation. A total of 165 FPs finally signed the research contract.

Questionnaire

Five months after the CIRANO project was completed, all the participating physicians were sent an anonymous questionnaire containing 4 sections: (1) demographic and practice data, (2) initial motivation to participate, (3) evaluation of the logistics of the project, and (4) motivation to participate in future projects. The evaluation questions were Likert-type (a scale of 4 answer categories); motivation was analyzed by asking respondents to indicate the 3 most important reasons from a list of 8 Table 1. A reminder was sent 1 month after the first mailing. Data from the questionnaire, as well as the number of patients included in the study, were entered in SPSS for Windows software version 8.5 for analysis (SPSS, Inc; Chicago, Ill). Questionnaires that were not fully completed were excluded.

Analysis

To calculate odds ratios the number of recruited patients per FP was dichotomized, with cut-off points at the 25th percentile of inclusion: 0 to 4 versus 5 or more patients for inclusion in the cohort study, and 0 or 1 patient versus 2 or more for inclusion in the clinical trial. The association between demographic data, motivating factors and the number of recruited patients was calculated and expressed as an odds ratio (with 95% confidence interval [CI]). Factors that were thus associated with recruitment at a P level of less than 0.25 (so as not to exclude potentially important variables), together with 7 factors known from the literature to be relevant (sex, list size, years in practice, practice location, research experience, high specialization, and financial incentive-driven motivation) were entered in a logistic regression model.

Using a stepwise-backward procedure, determinants of maximal inclusion were analyzed and reported as adjusted odds ratio (with 95% CI). As the workload and the financial incentive for the clinical trial and cohort study differed significantly, we analyzed inclusion in the 2 parts of the research project separately.

Results

Of the 165 participating FPs, 132 returned the questionnaire; the response rate was 80%. Since 4 of the questionnaires were incomplete, data from 128 family physicians could be used for analysis. Most responders were men (87%), and half had been in practice for more than 5 years, primarily in semi-urban areas of the Netherlands (68%). Most (77%) were involved in other professional activities, such as vocational training, continuing medical education (CME), or activities of the College of Family Physicians (CFP) at the district level. Half the responders worked in a group practice, and more than 60% of the practices were “specialized” (defined as performing at least 4 of the following clinical activities in routine daily practice: minor surgery, Doppler studies, electrocardiography, cervical screening, intrauterine device insertion, diabetes protocol, or spirometry). Also, 57% of the participants had previous research experience.

The initial motivation for participation in the project varied Table 1. For the majority of the participants, the research topic and the participation of our academic research group were the most important factors. One third of the respondents considered participation a professional obligation, were attracted by the personal appeal by the research group, or were intrigued by the presentation of the project. The involvement of the sponsor and the financial incentive were important for only a minority in their decision to participate.

In general, the project was well evaluated; 80% of the respondents stated that the project had met their expectations (56% fully, 24% partially), and 60% noted that they would consider participation in a similar research project in the future. More specifically, the participants were satisfied with the quality of the correspondence, the newsletter, and the monitoring of the project Table 2. However, 47% of the participating FPs thought that the overall time investment in the project was too burdensome, and one third mentioned the negative impact the application of the GCP guidelines had on the workload of the project.

From September 1996 until January 1998 these 128 physicians recruited 793 patients in the cohort phase of the study (average = 6.3 per FP; standard deviation [SD]=6.6) and 527 in the clinical trial (average = 4.2 per FP; SD=4.9). A total of 15% of the FPs recruited no patients in the cohort study, while 59% recruited 4 or more patients. In comparison, 21% of the FPs did not recruit any patients in the clinical trial, and 65% recruited 2 or more patients.

In the univariate analysis only the factors “active in CME/CFP” and “motivation by the academic research group” were associated with the number of recruited patients. These associations occurred in both the cohort study and the randomized clinical trial Table 3. After entering these 2 factors were entered in a logistic model, together with 7 factors earlier reported relevant in the literature, multivariate analysis indicated that only the factor “motivation by the participation of the academic research group” predicted the number of patients recruited in cohort study (adjusted odds ratio [OR] = 3.5; 95% CI, 1.4-9.0) and clinical trial (adjusted OR = 2.9; 95% CI, 1.2-6.9).

Discussion

The combination of participation in research and daily clinical practice requires a major time investment. Even though FPs consider their participation thoroughly before a research project commences, the actual numbers of patients they recruit are often disappointing.

In this large randomized trial on dyspepsia in primary care we showed that those FPs whose motivation was driven by the participation of an academic department of family medicine in the research group recruited the most patients. They were 3 times more likely than their colleagues to recruit at least 2 patients for the clinical trial or 5 patients for the cohort. Other factors such as list (practice) size, involvement in professional CME/CFP activities, research experience, and financial incentive may have played a role in the FPs’ decision to participate in the research project but were not associated with the actual number of patients they recruited.

As in most projects, a minority of the participating physicians did not manage to recruit any patients. These colleagues either underestimated the time investment required, had second thoughts about the acceptability for their patients, or were disappointed by the planning and paperwork of the project.

Factors determining patient recruitment in primary care research have hardly been studied. Busy schedules, forgetfulness, poor patient compliance, and FP involvement in too many projects are a few of the reasons given to explain poor recruitment.^18,9

One third of all Dutch FPs were invited to participate in the dyspepsia study. Even though bias might have been caused by either the subject (dyspepsia physicians), the fact that half of the FPs had experience in research, or the fact that the participants were generally very active in numerous professional activities (active physicians), we think the results of our study can be generalized to the primary care setting in the Netherlands. Our conclusions may, however, require modification in other countries because of differences in practice organization and research climate in primary care.

Although there were various reasons for participation in the CIRANO study, they are consistent with earlier reports. FPs who participated in our dyspepsia project were mainly motivated by the subject and by the fact that the project was affiliated with our academic primary care research group. The motivation was not a matter of personal acquaintance, since most of the participants were not known to the members of the research group.

A substantial number of the participating colleagues also felt that participation was a professional obligation. This perception might have been induced by the fact that during the introduction of the project, special emphasis was put on the evidence missing from certain paragraphs of the Dutch guidelines on dyspepsia and on the need for primary care-based research to fill this gap. Although the research group felt that this was an important aspect of motivation, the evaluation showed that while it was an important reason to participate, it was not independently associated with patient recruitment. Only 10% of the participants stated that the financial incentive was a major reason to participate. Although this could be an unrealistic subjective statement, multivariate analysis confirmed that incentive-driven motivation was not related to the number of patients recruited. The fact that the results were the same for both the cohort study and the clinical trial might also be an indication that the amount of the incentive played a minor role in patient recruitment. This confirms earlier reports^12,13 that FPs probably do not participate in research for the money, although they do want a proper reimbursement for the time invested.

The fact that the majority of our study group were involved in professional education or organization confirms once again¹⁵ that active colleagues are the ones most motivated for research. Interest in research, however, obviously does not guarantee successful inclusion. Although a high level of practice organization and a high specialization in clinical activities have also reportedly been associated with optimal recruitment, we could not confirm this with our data.

Conclusions

Collaborators for primary care research projects should primarily be sought among the colleagues who are already active in different professional fields, and who have a strong affiliation with academic research. Successful participation is mainly determined by the initial motivation of the FP: Those who are motivated by the presence of an academic research group in the study recruit best. The research topic, the amount of the financial incentive, research experience, and other factors often suggested to influence patient recruitment are probably less important.

Research in primary care is a growing field; the need for research on new diagnostic and therapeutic methods, the prognostic value of clinical signs and symptoms, and the effectiveness of clinical strategies in the population where these clinical contributions will be applied is well recognized.^1-5 The number and scale of research projects in primary care is expanding continuously, and research networks are being established.^6-8 This development, however, is putting increasing pressure on family physicians (FP) to actively participate in research. From an FP’s perspective there is a delicate balance between active research participation and efficient clinical practice.⁹ Proper planning to minimize paperwork and the delegation of research logistics to practice assistants can avoid many practical obstacles.^7,10,11

Motivating and recruiting FPs to participate is an essential step in conducting primary care research. Factors such as the clinical relevance of the research subject, personal interest in the topic, ownership, personal contact with the research group, and the required time investment have been shown to influence the participation of FPs.^5,11-15

Earlier studies have shown that higher-qualified physicians (with more continuing medical education training or a degree in research), physicians involved in under-or postgraduate training, FPs with research experience, and physicians working in well-organized practices (with more practice assistants and management protocols) are more interested in participating in research. Sex, the number of physicians per practice, and wages do not influence participation.¹⁵ The actual impact of financial incentives, however, is unclear. One study reported that incentives raised participation,¹⁶ while others could not confirm this.^12,15 Some have also drawn attention to the ethical and methodologic aspects of payment for research.^5,17

After successfully contracting with FPs to recruit patients for the study, the next task for a research group is to attain the maximal recruitment of patients. Unfortunately, less than half of the participating physicians actually recruit patients in the research project,^9,12,18 and often only a minority (20%)¹⁸ of the eligible patients are actually included. Our objective in this study was to identify practice and physician characteristics determining successful patient recruitment among FPs participating in a combined randomized clinical trial/cohort study on drug treatment of dyspepsia in the Netherlands.

Methods

Setting

Our data were compiled from a practice-based research network (PBRN) used for a primary care study of dyspepsia, the CIRANO study (Cisapride or Ranitidine in NonOrganic dyspepsia), which was conducted from 1996-1998 in the Netherlands. The CIRANO project consisted of 2 parts: a cohort study, in which dyspeptic patients were included and followed up for 1 year, and a randomized clinical trial in which patients selected from the cohort were treated with either an H2 blocker or a prokinetic drug.¹⁹ It was designed by the dyspepsia group of the Julius Centre, a group of primary care researchers who have been involved in gastrointestinal research and guideline development in the Netherlands for a number of years. Janssen Cilag Inc. was the sole sponsor of the project. The protocol was approved by the academic ethical committee, and data monitoring was done in accordance with the GCP guidelines (good clinical practice, a government protocol for conducting drug trials).

In the cohort study the workload for the participating physicians was small. After identification and inclusion by the FP, patients had to complete a validated dyspepsia symptom score, a quality of life questionnaire (COOP/WONCA chart), and a mental health state check list (GHQ 12). Also, the practice assistant performed a Helicobacter pylori whole- blood test. Follow-up of the patient was done by the research group. The FP workload in the clinical trial was heavier. After inclusion, the patients were randomized to one of the treatment arms, treated for 4 weeks, and followed up for 3 months. Patients were seen by the FP at inclusion and after 1 and 3 months.

Monitoring, data recording, and verification were performed by a clinical research organization under supervision of the research group. Data were stored and analyzed by the group.

FPs were given a financial incentive for each patient they included. It comprised a reimbursement for the extra practice time spent completing the research protocol. The estimated overall time investment for FPs was 2 hours with an additional 5 minutes for each patient included in the cohort and 1 additional hour for each patient included in the randomized clinical trial. Since the workload differed significantly, the reimbursement was higher for the patients included in the clinical trial ($25 per patient in the cohort, $70 for each patient in the randomized clinical trial). Also, project bulletins were distributed regularly during the course of the project.

All FPs in the academic network of the Utrecht University (2000 FPs, one third of all Dutch FPs) were invited by the academic research group to participate in the CIRANO study. Two hundred of them expressed interest in the study and asked for documentation. A total of 165 FPs finally signed the research contract.

Questionnaire

Five months after the CIRANO project was completed, all the participating physicians were sent an anonymous questionnaire containing 4 sections: (1) demographic and practice data, (2) initial motivation to participate, (3) evaluation of the logistics of the project, and (4) motivation to participate in future projects. The evaluation questions were Likert-type (a scale of 4 answer categories); motivation was analyzed by asking respondents to indicate the 3 most important reasons from a list of 8 Table 1. A reminder was sent 1 month after the first mailing. Data from the questionnaire, as well as the number of patients included in the study, were entered in SPSS for Windows software version 8.5 for analysis (SPSS, Inc; Chicago, Ill). Questionnaires that were not fully completed were excluded.

Analysis

To calculate odds ratios the number of recruited patients per FP was dichotomized, with cut-off points at the 25th percentile of inclusion: 0 to 4 versus 5 or more patients for inclusion in the cohort study, and 0 or 1 patient versus 2 or more for inclusion in the clinical trial. The association between demographic data, motivating factors and the number of recruited patients was calculated and expressed as an odds ratio (with 95% confidence interval [CI]). Factors that were thus associated with recruitment at a P level of less than 0.25 (so as not to exclude potentially important variables), together with 7 factors known from the literature to be relevant (sex, list size, years in practice, practice location, research experience, high specialization, and financial incentive-driven motivation) were entered in a logistic regression model.

Using a stepwise-backward procedure, determinants of maximal inclusion were analyzed and reported as adjusted odds ratio (with 95% CI). As the workload and the financial incentive for the clinical trial and cohort study differed significantly, we analyzed inclusion in the 2 parts of the research project separately.

Results

Of the 165 participating FPs, 132 returned the questionnaire; the response rate was 80%. Since 4 of the questionnaires were incomplete, data from 128 family physicians could be used for analysis. Most responders were men (87%), and half had been in practice for more than 5 years, primarily in semi-urban areas of the Netherlands (68%). Most (77%) were involved in other professional activities, such as vocational training, continuing medical education (CME), or activities of the College of Family Physicians (CFP) at the district level. Half the responders worked in a group practice, and more than 60% of the practices were “specialized” (defined as performing at least 4 of the following clinical activities in routine daily practice: minor surgery, Doppler studies, electrocardiography, cervical screening, intrauterine device insertion, diabetes protocol, or spirometry). Also, 57% of the participants had previous research experience.

The initial motivation for participation in the project varied Table 1. For the majority of the participants, the research topic and the participation of our academic research group were the most important factors. One third of the respondents considered participation a professional obligation, were attracted by the personal appeal by the research group, or were intrigued by the presentation of the project. The involvement of the sponsor and the financial incentive were important for only a minority in their decision to participate.

In general, the project was well evaluated; 80% of the respondents stated that the project had met their expectations (56% fully, 24% partially), and 60% noted that they would consider participation in a similar research project in the future. More specifically, the participants were satisfied with the quality of the correspondence, the newsletter, and the monitoring of the project Table 2. However, 47% of the participating FPs thought that the overall time investment in the project was too burdensome, and one third mentioned the negative impact the application of the GCP guidelines had on the workload of the project.

From September 1996 until January 1998 these 128 physicians recruited 793 patients in the cohort phase of the study (average = 6.3 per FP; standard deviation [SD]=6.6) and 527 in the clinical trial (average = 4.2 per FP; SD=4.9). A total of 15% of the FPs recruited no patients in the cohort study, while 59% recruited 4 or more patients. In comparison, 21% of the FPs did not recruit any patients in the clinical trial, and 65% recruited 2 or more patients.

In the univariate analysis only the factors “active in CME/CFP” and “motivation by the academic research group” were associated with the number of recruited patients. These associations occurred in both the cohort study and the randomized clinical trial Table 3. After entering these 2 factors were entered in a logistic model, together with 7 factors earlier reported relevant in the literature, multivariate analysis indicated that only the factor “motivation by the participation of the academic research group” predicted the number of patients recruited in cohort study (adjusted odds ratio [OR] = 3.5; 95% CI, 1.4-9.0) and clinical trial (adjusted OR = 2.9; 95% CI, 1.2-6.9).

Discussion

The combination of participation in research and daily clinical practice requires a major time investment. Even though FPs consider their participation thoroughly before a research project commences, the actual numbers of patients they recruit are often disappointing.

In this large randomized trial on dyspepsia in primary care we showed that those FPs whose motivation was driven by the participation of an academic department of family medicine in the research group recruited the most patients. They were 3 times more likely than their colleagues to recruit at least 2 patients for the clinical trial or 5 patients for the cohort. Other factors such as list (practice) size, involvement in professional CME/CFP activities, research experience, and financial incentive may have played a role in the FPs’ decision to participate in the research project but were not associated with the actual number of patients they recruited.

As in most projects, a minority of the participating physicians did not manage to recruit any patients. These colleagues either underestimated the time investment required, had second thoughts about the acceptability for their patients, or were disappointed by the planning and paperwork of the project.

Factors determining patient recruitment in primary care research have hardly been studied. Busy schedules, forgetfulness, poor patient compliance, and FP involvement in too many projects are a few of the reasons given to explain poor recruitment.^18,9

One third of all Dutch FPs were invited to participate in the dyspepsia study. Even though bias might have been caused by either the subject (dyspepsia physicians), the fact that half of the FPs had experience in research, or the fact that the participants were generally very active in numerous professional activities (active physicians), we think the results of our study can be generalized to the primary care setting in the Netherlands. Our conclusions may, however, require modification in other countries because of differences in practice organization and research climate in primary care.

Although there were various reasons for participation in the CIRANO study, they are consistent with earlier reports. FPs who participated in our dyspepsia project were mainly motivated by the subject and by the fact that the project was affiliated with our academic primary care research group. The motivation was not a matter of personal acquaintance, since most of the participants were not known to the members of the research group.

A substantial number of the participating colleagues also felt that participation was a professional obligation. This perception might have been induced by the fact that during the introduction of the project, special emphasis was put on the evidence missing from certain paragraphs of the Dutch guidelines on dyspepsia and on the need for primary care-based research to fill this gap. Although the research group felt that this was an important aspect of motivation, the evaluation showed that while it was an important reason to participate, it was not independently associated with patient recruitment. Only 10% of the participants stated that the financial incentive was a major reason to participate. Although this could be an unrealistic subjective statement, multivariate analysis confirmed that incentive-driven motivation was not related to the number of patients recruited. The fact that the results were the same for both the cohort study and the clinical trial might also be an indication that the amount of the incentive played a minor role in patient recruitment. This confirms earlier reports^12,13 that FPs probably do not participate in research for the money, although they do want a proper reimbursement for the time invested.

The fact that the majority of our study group were involved in professional education or organization confirms once again¹⁵ that active colleagues are the ones most motivated for research. Interest in research, however, obviously does not guarantee successful inclusion. Although a high level of practice organization and a high specialization in clinical activities have also reportedly been associated with optimal recruitment, we could not confirm this with our data.

Conclusions

Collaborators for primary care research projects should primarily be sought among the colleagues who are already active in different professional fields, and who have a strong affiliation with academic research. Successful participation is mainly determined by the initial motivation of the FP: Those who are motivated by the presence of an academic research group in the study recruit best. The research topic, the amount of the financial incentive, research experience, and other factors often suggested to influence patient recruitment are probably less important.