Studies Funded by Pharma 30 Times More Likely to Report Higher Efficacy Estimates for Drugs

The report summarizes key findings from a three-day NASEM-sponsored workshop on conflicts of interest in health research.

Workshop participants presented research showing how corporate funding influences research agendas, project design and principal investigator appointments and also how it biases the way researchers analyze, report and disseminate their findings.

Roundtable discussions debated possible solutions.

“We just can’t allow corporate PR and product defense to pass as science anymore,” U.S. Right to Know Executive Director Gary Ruskin said during a panel discussion he moderated.

Participants included university researchers, officials from public health agencies and a representative from the Health Effects Institute (HEI), which facilitates public-private partnerships. It also included a representative from drugmaker AstraZeneca.

Research on bias ‘raised some red flags’

Lisa Bero, Ph.D., an expert on industry bias in research from the University of Colorado Anschutz Medical Center, provided a framework for the report, presenting overview studies concluding there is “very strong evidence” that scientific research is consistently biased in favor of research sponsors.

Those biases express themselves in a number of different ways, Bero, chief scientist at the Center for Bioethics and Humanities reported.

For example, a meta-analysis of 3,000 studies found that industry-sponsored studies were 30 times more likely than non-industry-sponsored studies to report statistically significant efficacy estimates for drugs.

In another example, Bero and a colleague analyzed studies of the effects of second-hand smoke. “Tobacco industry-sponsored reviews were almost 90 times more likely to conclude that secondhand smoke was not harmful,” they reported.

“That raised some red flags,” Bero said.

Industry funding also affects the way researchers write their conclusions, regardless of the actual results of the study. This is a problem, according to Bero, because lay media often summarize the more accessible conclusions, rather than the results of a study.

For example, The Defender reported the authors of a study that found a safety signal for myocarditis in children concluded that the signal was evidence the vaccines were safe for kids.

Corporate sponsors even drive the research agenda itself, and those agendas “rarely align with public health questions or prevention,” Bero said.

For example, the gambling industry funds research on the genetic causes of addiction — fueling theories that addiction is something natural that can’t be addressed by policies limiting the industry.

Or, Coca-Cola funds more research on exercise than on the effects of sugar intake on the body.

Industry also influences research design. Twenty-six of the 165 signatories to the Brussels Declaration on Ethics and Principles for Science and Society Policy-Making were associated with the tobacco or alcohol industries — and the declaration laid out a plan for influencing science policy that had been created 20 years prior by the tobacco industry.

Although many journals now require investigators to list their conflicts of interest, Bero and her colleague found that supposed transparency around conflicts of interest does not guarantee the sponsors play no role in the study.

They interviewed the lead researcher in 200 industry-funded drug trials, all of which had statements saying the funder had no role in the study.

But lead investigators of those studies reported that the sponsor was involved in study design in 92% of the studies, involved in data analysis in 73% of the studies and involved in reporting the findings in 87% of the studies. Only 33% of the authors said they had final say on what appeared in the publication.

Commenting on this phenomenon, Nicholas Chartres, Ph.D., collaborator and former director of Science & Policy, Program on Reproductive Health and the Environment at the University of California, San Francisco, said there has been a lot of focus on conflict of interest disclosure as a way to resolve the problem of industry bias.

But, he said, even when researchers make their conflicts of interest transparent, that “certainly doesn’t safeguard the science from being protected from potential influence.”

He said a larger problem that is difficult to address is that the systematic reviews often used to make public health recommendations “can be misled in part because of industry influence in the underlying studies being synthesized.”

Unless researchers come up with a way to assess that influence, even those broader analyses that aren’t funded by industry will tend to favor it anyway, he said.

Proposals to protect ‘independence and quality’?

Proposals put forward to deal with these issues included a discussion of several existing models. For example, a presentation from the NIH explained how it “protects the independence of research and prompt[s] transparency” by setting policies requiring multiple rounds of peer review and conflict-of-interest statements.

AstraZeneca said it uses a bioethics approach to maintain clinical research integrity.

The nonprofit HEI, which focuses on the auto industry, described its model of creating an oversight board made up of U.S. Environmental Protection Agency and industry-approved participants, but that it commits to publishing all study results, both positive and negative.

Ruskin, who acted as a reviewer for the NASEM report, said he saw public-private partnerships such as the one proposed by HEI as a “non-starter” in the health industry.

He added:

“I think we should have zero illusions about the effectiveness of corporate self-regulation of research ethics because it’s not binding. There are no penalties for corporations for violating these ethics guidelines, their own internal ethics guidelines, and corporate codes of conduct can be weakened or abrogated at any moment.

“That’s why solutions to these health research ethics problems will come through federal and state law and policy and not corporate self-regulation.”

The final chapter of the report addressed potential new models and principles to protect the independence and quality of scientific research.

Participants suggested that more clear policies were needed to eliminate or mitigate conflicts of interest. Dr. Sunita Sah said that disclosure was an insufficient solution if it was not paired with a re-orientation by providers of professional norms and principles that prioritized patients and the public over profit-making.

Other proposals included setting rules that sponsors should not be allowed to play any role in study design or reporting.

Quinn Grundy R.N., Ph.D., said that framing the problem as needing to eliminate corporate funding altogether from clinical trials, or transitioning to a public funding model is “insurmountable because of lack of political will.”

But Ruskin emphasized the need for deeper systemic change:

“The message has to come from the top, from our President, from our Congress, from our governors, from our state legislatures. We have to tell the truth to the American people that our current health evidence base may well not be that reliable, and that as a matter of federal and state policy, we are going to do better.

“We are going to build a health evidence base that we the people can trust and believe in, and that means one that is as free as possible from commercial influences.

“And especially that our regulatory decisions and policy must be based on clean and uncorrupted science. We just have to do this. So many lives are at stake.”

Would public funding resolve conflicts of interest issues?

The report and workshop focused on how scientific investigation was affected by industry funding and many researchers called for more public funding to resolve the issue.

But the conference did not address the fact that many public institutions also are influenced by industry funding.

That includes the question of how corporate funding has influenced NASEM itself. As The New York Times revealed in April, NASEM continued to accept funding from the Sackler family, owners of Purdue Pharma, the maker of Oxycontin, while shaping federal policy on the opioid crisis.

And internal emails obtained via a Freedom of Information Act request by the plaintiffs in Food and Water Watch v. EPA revealed the American Dental Association was working to privately influence the “independent” NASEM.

Public health agencies like the U.S. Food and Drug Administration get the majority of their funding directly from the pharmaceutical companies whose drugs they are approving.

The National Institutes of Health (NIH) profits from the interventions it develops and licenses to pharmaceutical companies and the inventors, who work for the NIH, also individually receive up to $150,000 per year for their patentable inventions, depending on how much the NIH receives in royalties.

A 2020 Government Accountability Office report found NIH was not transparent about the profits that come from its drugs.

And agencies like the NIH give away millions in research funding to investigators with conflicts of interest, such as a recent $4.7 million grant to Merck consultant Noel Brewer, Ph.D., to investigate how to increase uptake of the human papillomavirus vaccine, which Merck manufacturers.