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Poor study design and the tendency to publish positive—but not negative—results threaten the validity of preclinical research, according to an article published in eLife.
“Only a fraction of drugs that show promise in animals end up proving safe and effective in humans,” said study author Jonathan Kimmelman, PhD, of McGill University in Montreal, Quebec, Canada.
“An important reason is because studies in animals are often not well designed and because positive results have a higher chance of being published. They end up skewing what we think we know about the potential of a drug.”
Dr Kimmelman and his colleagues came to this conclusion after evaluating all published animal studies of sunitinib, a drug used to treat advanced kidney cancer, a rare type of stomach cancer, and rare tumors of the neuroendocrine system.
The investigators found evidence to suggest that studies reporting little or no anticancer effect were simply not published, leading anticancer effects of the drug to be overestimated by as much as 45%.
The team noted, however, that these findings do not raise any concerns about the clinical use of sunitinib.
Dr Kimmelman and his colleagues also found that few studies used practices like blinding or randomization. And it was often unclear how many animals had been tested because the sample size was not reported.
The drug was tested against different cancers, and all types tested showed statistically significant anticancer activity, a result that “strains credibility”, according to Dr Kimmelman.
He added that researchers failed to observe the dose-dependent response to the drug that is known to occur in humans.
Finally, the researchers did not test the drug on a range of animal models, focusing instead on juvenile female mice with a compromised immune system. Malignancies tested in a wider range of animal types, such as mice that have spontaneously developed tumors, showed less extreme effect sizes.
“Preclinical research is plagued by poor design and reporting practices, exposing patients to harmful and inactive agents, wasting time in the lab, and driving up the price of drugs,” Dr Kimmelman said.
“Our findings provide compelling reasons for developing and implementing guidelines for the design and reporting of preclinical studies in cancer, similar to those already in use for stroke, epilepsy, and cardiology.” 
Poor study design and the tendency to publish positive—but not negative—results threaten the validity of preclinical research, according to an article published in eLife.
“Only a fraction of drugs that show promise in animals end up proving safe and effective in humans,” said study author Jonathan Kimmelman, PhD, of McGill University in Montreal, Quebec, Canada.
“An important reason is because studies in animals are often not well designed and because positive results have a higher chance of being published. They end up skewing what we think we know about the potential of a drug.”
Dr Kimmelman and his colleagues came to this conclusion after evaluating all published animal studies of sunitinib, a drug used to treat advanced kidney cancer, a rare type of stomach cancer, and rare tumors of the neuroendocrine system.
The investigators found evidence to suggest that studies reporting little or no anticancer effect were simply not published, leading anticancer effects of the drug to be overestimated by as much as 45%.
The team noted, however, that these findings do not raise any concerns about the clinical use of sunitinib.
Dr Kimmelman and his colleagues also found that few studies used practices like blinding or randomization. And it was often unclear how many animals had been tested because the sample size was not reported.
The drug was tested against different cancers, and all types tested showed statistically significant anticancer activity, a result that “strains credibility”, according to Dr Kimmelman.
He added that researchers failed to observe the dose-dependent response to the drug that is known to occur in humans.
Finally, the researchers did not test the drug on a range of animal models, focusing instead on juvenile female mice with a compromised immune system. Malignancies tested in a wider range of animal types, such as mice that have spontaneously developed tumors, showed less extreme effect sizes.
“Preclinical research is plagued by poor design and reporting practices, exposing patients to harmful and inactive agents, wasting time in the lab, and driving up the price of drugs,” Dr Kimmelman said.
“Our findings provide compelling reasons for developing and implementing guidelines for the design and reporting of preclinical studies in cancer, similar to those already in use for stroke, epilepsy, and cardiology.”
Poor study design and the tendency to publish positive—but not negative—results threaten the validity of preclinical research, according to an article published in eLife.
“Only a fraction of drugs that show promise in animals end up proving safe and effective in humans,” said study author Jonathan Kimmelman, PhD, of McGill University in Montreal, Quebec, Canada.
“An important reason is because studies in animals are often not well designed and because positive results have a higher chance of being published. They end up skewing what we think we know about the potential of a drug.”
Dr Kimmelman and his colleagues came to this conclusion after evaluating all published animal studies of sunitinib, a drug used to treat advanced kidney cancer, a rare type of stomach cancer, and rare tumors of the neuroendocrine system.
The investigators found evidence to suggest that studies reporting little or no anticancer effect were simply not published, leading anticancer effects of the drug to be overestimated by as much as 45%.
The team noted, however, that these findings do not raise any concerns about the clinical use of sunitinib.
Dr Kimmelman and his colleagues also found that few studies used practices like blinding or randomization. And it was often unclear how many animals had been tested because the sample size was not reported.
The drug was tested against different cancers, and all types tested showed statistically significant anticancer activity, a result that “strains credibility”, according to Dr Kimmelman.
He added that researchers failed to observe the dose-dependent response to the drug that is known to occur in humans.
Finally, the researchers did not test the drug on a range of animal models, focusing instead on juvenile female mice with a compromised immune system. Malignancies tested in a wider range of animal types, such as mice that have spontaneously developed tumors, showed less extreme effect sizes.
“Preclinical research is plagued by poor design and reporting practices, exposing patients to harmful and inactive agents, wasting time in the lab, and driving up the price of drugs,” Dr Kimmelman said.
“Our findings provide compelling reasons for developing and implementing guidelines for the design and reporting of preclinical studies in cancer, similar to those already in use for stroke, epilepsy, and cardiology.”