A study by US and Canadian researchers has once again underlined the need for wide-ranging transparency in the publication of clinical trials and their outcomes.
While the analysis of studies listed on the US public registry ClinicalTrials.gov extended only to 2006, a year before the Food and Drug Administration started requiring sponsors to register their trials (other than Phase I) with ClinicalTrials.gov on launch, the results will give plenty of fuel to critics who believe bias is endemic in industry-funded research.
Notably, out of 362 clinical trials with published results, industry-sponsored studies reported positive outcomes in 85.4% of cases, compared with 50.0% for government-funded trials and 71.9% for those backed by non-profit or non-federal organisations. Studies funded by non-profit or non-federal organisations with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% versus 61.2%).
Moreover, industry-sponsored trials were the least likely of the three categories to have published results within two years of study completion. The two-year publication rate was 32% for industry trials compared with 54% for government trials and 56% for those funded solely by non-profit or non-federal organisations.
“While we cannot specifically point to which factors contribute to the association between funding source and positive result reporting, our findings speak to the need for more disclosure of all elements of a study,” commented lead author Dr Florence Bourgeois of Children’s Hospital Boston.
A number of biases may be involved
“Publication bias is likely a contributing factor, but there may be many more, including biases in study design, patient selection, data analysis and results reporting.”
The Pharmaceutical Research and Manufacturers of America (PhRMA), however, insisted the analysis, funded by the US National Library of Medicine and the National Institute of Child Health and Human Development, “demonstrates one more way that patients and the public health can benefit from increased transparency”.
The study “would not have been possible without the large volume of information about ongoing and completed industry-sponsored clinical trials provided through ClinicalTrials.gov and supported by PhRMA and its member companies”, it added, highlighting the industry’s “longstanding commitment to the ethical conduct of clinical trials and to increasing transparency by reporting more information about clinical trials”.
Dr Bourgeois and colleagues – Dr Kenneth Mandl from Children’s Hospital Boston and, in the interests of transparency, Dr Srinivas Murthy from the Hospital for Sick Children in Toronto, Canada (a press release issued by Children’s Hospital Boston neglected to mention Dr Murthy’s involvement) – reviewed a total of 546 safety and efficacy trials for cholesterol-lowering drugs, antidepressants, antipsychotics, proton pump inhibitors and vasodilators conducted between 2000 and 2006 and listed on ClinicalTrials.gov. The research was published in the 3 August issue of the Annals of Internal Medicine.
Of these trials, 63% were primarily funded by industry, 14% by government and 23% by non-profit or non-federal organisations. The industry-sponsored studies were more likely (88.7%) to be Phase III or IV trials, to use an active comparator in controlled trials (36.8%), to be multicentre studies (89.0%) and to enrol more participants (median sample size = 306).
Positive late-stage trials ‘a mitigating factor’
PhRMA picked up on the industry tendency to fund later-stage research as a mitigating factor. “As the authors note, later-stage trials may be more likely to have positive outcomes, because there is more certainty about the drug’s efficacy and safety at this advanced stage in the drug development cycle,” the association stated.
As the researchers pointed out, though, even those Phase I and II trials funded by industry reported the highest percentage of favourable outcomes.
The research team also acknowledged that industry is likely to be more selective in the trials it funds, helping to account for the higher proportion of favourable outcomes. “Industry is very good at knowing what they want to study, and industry-sponsored studies are more efficient and well funded,” Dr Bourgeois commented. “But despite these potential biases, this is a stunning result.”
