Influence of pharmaceutical funding on the conclusions of meta-analyses

Differences in interpretation of results between meta-analyses funded by drug companies and those that are not rightly raise concerns about the reliability of studies funded by the industry.12345

In this week’s BMJ, Yank and colleagues offer further proof of the potential influence that the drug industry has on the outcomes of the studies they fund.6 The study assesses the correlation between the “results” of meta-analyses about hypertensive drugs and the “conclusions” their authors draw from them. Even if we allow for the inevitable subjectivity of Yank and colleagues’ review of the included meta-analyses and for the other potential sources of bias they recognise—unblinded review and somewhat arbitrary measures of financial ties—the key findings are likely to be robust and will draw the ire of the many critics of the drug industry.

Yank and colleagues show that studies funded by a single drug company have a 55% rate of favourable results that is transformed into a 92% rate for favourable conclusions, representing a 37% gap. The gap shrinks to 21% (57% to 79%) when two or more drug companies provide support. Yet the gap vanishes entirely for studies done by non-profit institutions alone or even in conjunction with drug companies. The clear inference is that impartial studies are more reliable. What accounts for these results? And what should be done about them?

In terms of explaining the results, the sample size of 124 studies is too small to allow the analysis to be broken down into smaller categories. Such refinement might be helpful to identify what characteristics beyond “financial tie” might account for the better or worse performance within studies funded by a single drug company. How much direct control does the drug company exercise over the study? Do its own doctors participate? These questions matter because any bias that asserts itself in meta-analyses is unlikely to disappear in ordinary clinical trials, where company experts commonly team up with outside experts. The proper mix of personnel and the introduction of sensible safeguards for independence could prove valuable in reducing any actual or perceived bias. Increased confidence in clinical trials remains vital, even if the actual skew in these areas turns out to be less robust than the one found in this study.

It has been suggested that drug companies should have a more restricted role in financing and organising clinical trials generally.12345 One proposal suggests that drug companies should contribute money to research institutions, which then spend the funds on whatever research they regard as appropriate.7 But if we push too hard with these recommendations, industry support may dry up.8 9 Around 40% of the studies Yank and colleagues analysed were done by single drug companies. Only slightly more than 20% were done by non-profit making organisations. At a guess, the 20% of the studies that had “no statement” would be distributed in a similar ratio—8% would be funded by a single drug company and only 4% by a non-profit making organisation. Accordingly, any strong prohibition on the involvement of drug companies would reduce the number of studies conducted by more than 60% if studies funded by multiple drug companies were also prohibited. We are unlikely to be able to find large new sources of funding under current circumstances.

We therefore face a dilemma. Do we want fewer studies of presumably better quality, or do we want more studies whose quality may be more biased? I would opt for the last option. Nothing in the work of Yank and colleagues suggests that the raw data from the drug sponsored studies were defective. The criticisms are directed to the optimistic inferences drawn from data. But these inferences are drawn from publicly available sources, which other investigators could presumably check without having to re-collect the original data from scratch. A sensible approach might be to encourage further dialogue by asking for editorial comment. These commentaries need not appear in the same journals as the original studies, assuming they are published. The commentaries could be published elsewhere to offer a balanced perspective, and the original authors could be invited to respond to any criticisms. In all likelihood, these critiques will subtly induce original authors to soften their basic claims.

Legal restrictions or requirements do not need to be imposed on drug company funding or participation in these studies. The medical profession already has voluntary means to improve its performance. As long as the disagreements lie in the interpretation of data and not the collection of data, the solution is not state regulation; rather, doctors should be warned to be cautious in interpreting the conclusions of studies. Indeed, the largest problem for drug innovation does not lie with these studies, but in the ever greater time and money needed to bring new drugs to market, where the price of delay is too often measured in lives lost.