Connections : Join the Conversation - The blog of Biomet CEO Jeffrey R. Binder

In our last blog, we examined the criticism surrounding industry funding of continuing medical education (CME). In this installment, we turn to industry funding of clinical research, which critics claim creates bias and undermines public trust in medicine.

Marcia Angell, MD, former editor of the New England Journal of Medicine and a leading critic of industry funding of clinical research, framed the issue explicitly:

"It is self-evidently absurd to look to investor-owned companies for unbiased evaluations of their own products."¹

Industry funds approximately 75% of clinical trials in the United States², and 58% of all biomedical research.³ Dr. Angell and other critics would like to substitute those funds with something else, but have yet to demonstrate a pressing need to do so, let alone offer a practical source of replacement funding.

Why does industry fund healthcare professionals to conduct clinical research?

The design and evaluation of medical devices requires collaboration with experienced surgeons and other healthcare professionals who deserve to be paid for their time.

For example, a recent AAOS survey indicates that, on average, U.S. orthopedic surgeons are able to devote only 2% of their time to research.⁴ In order to complete a clinical trial, manufacturers require surgeon-investigators to shepherd study protocols through Institutional Review Boards (which charge a fee for reviewing clinical protocols), scrupulously track the patients' progress, complete numerous patient evaluation forms, and report the data. Publishing that data in a peer-reviewed journal requires an additional significant time commitment. Surgeons incur both direct and opportunity costs when conducting research. With increasing demands on their time from ever-growing regulations and patient volume, surgeons will simply—and reasonably—refuse to participate in research without fair compensation.

Given that research must be funded, and the increasing demands for clinical data on drugs and devices, the key question is: who should fund this research--industry or government?

Argument #1 against industry funding: It encourages bias in clinical research

The key argument for curtailing industry funding is that it creates financial conflicts of interest that encourage bias in clinical research. The Institute of Medicine (IOM) studied this issue exhaustively, and summarized its findings as follows:

"Thus, although there is little direct evidence that industry sponsorship has led to deliberate skewing of the results or reporting (emphasis added), there are multiple cases in which industry sponsors have withheld important study results and in which the conclusions presented in the reports appear to overstate the study findings. The risk of undue influence in research exists."⁵

In other words, IOM could not demonstrate systemic bias resulting from industry sponsorship of clinical research beyond a handful of cited anecdotes.

What about FDA clinical trials?

Industry sponsors a significant number of clinical investigations as part of the FDA review process. FDA oversight has proven to be very effective from a safety standpoint. Between 2005 and 2009, fewer than 1% of products submitted for FDA clearance or approval have been subject to Class 1 (most severe) recalls.⁶ The fact that over 99% of nearly 26,000 submissions did NOT result in a Class 1 recall is a strong indicator that FDA and industry have worked together effectively to deliver safe products to patients.

Additionally, FDA's data indicate that industry-sponsored researchers, as a rule, adhere to applicable regulations. FDA's Bioresearch Monitoring Information System lists 166,290 clinical investigators who have participated in 56,263 clinical trials from 2004-2008. During that time, only 33 investigators (.02%) have been restricted or disqualified from participating in future FDA trials. Stated differently, 99.98% of investigators are in good standing with FDA.⁷

Does the profit motive create bias?

Critics argue that financial incentives may prompt industry to pressure clinicians to fudge results, and that investigators, eager to please their sponsors, may be tempted to cooperate. In fact, the marketplace incentivizes companies to act in the public interest.

Ongoing clinical monitoring helps companies identify safety signals, allowing them to modify products to improve performance, or discontinue marketing if warranted. Valid clinical data helps companies market their products to providers and payors.

Conversely, companies cannot benefit in the long term from deceptive practices. Severe punishment awaits those companies that attempt to cut corners. Companies can incur billions of dollars in cost from lawsuits, penalties, and lost market share.

For example, analysts estimated that the fallout from the Vioxx® debacle would cost Merck as much as $18 billion—an estimated $8 billion more than the Vioxx® sold during the five years it was on the market.^8,9

Oversight of clinical research already in place

As with CME, it is not surprising that evidence of bias in industry-funded clinical research is scant, because it is highly regulated and monitored. Besides FDA's stringent oversight, which includes approval of studies for new products and inspections of study sponsors and investigators, the following protections are in place:

• The Office of Human Research Protection provides oversight of clinical trials regulated and funded by the federal government.¹⁰
• Institutional Review Boards must approve clinical trials conducted at healthcare institutions.
• Specialty societies promulgate guidelines for ethical conduct, including interactions with patients and industry sponsors of research.¹¹
• Industry councils, such as AdvaMed, publish guidelines for ethical interaction with healthcare providers.¹²
• Guidelines from the International Council of Medical Journal Editors promote transparency and access to clinical trial data submitted for publication.¹³

Simply put, clinical trial research is carefully scrutinized, from the initial protocol submission through publication.

Argument #2 against industry funding: It undermines public trust

The second key argument is that industry funding creates the perception of, if not actual, bias. David Korn, MD, former Chief Science Officer of the Association of American Medical Colleges, stated:

"...even the perception of faculty or institutional conflict of interest cannot be tolerated."¹⁴

But restricting industry funding of clinical research will not achieve this goal, for three reasons. First, it's unattainable, especially when industry critics are hell-bent on creating the perception.

It's also a fallacious standard, because the potential for bias cannot be predictably identified, let alone eradicated, regardless of the funding source.¹⁵

Additionally, there is no evidence that industry funding of clinical research undermines public trust. In fact, numerous surveys indicate that the public overwhelmingly approves of research collaborations among healthcare providers and industry.^16-19

IOM's report acknowledges that patients aren't concerned with financial conflicts of interest:

"...several surveys suggest that participants in clinical trials currently are not highly concerned about investigators' financial conflicts of interest. Most respondents report that their decision to enroll in a clinical trial would not be greatly affected by learning that the researcher had a financial relationship with the sponsor. Some respondents even believed that 'a greater financial interest would make the investigator do a better job.'" (Weinfurt et al., 2006a, p. 903)⁵

IOM then dismisses the data:

"...it is not clear that it is reasonable to expect the average [clinical trial] participant to understand these issues."⁵

Later, IOM candidly admits whose opinion really matters:

"The political and economic support of the research enterprise depends critically on the confidence of the opinion leaders in government, the media, and academia."⁵

Ironically, it is government, the media, and academia that are creating the potential for public distrust with their unsubstantiated narrative about the evils of industry funding.

Should the government be the sole source of clinical research funding?

Dr. Angell proposes that the National Institutes of Health (NIH) take over the administration of all pharmaceutical clinical trials¹ (although we have no doubt that such an initiative would eventually target medical device trials, too). Presumably, industry would fund clinical trials through a new tax or fee. This approach may be problematic.

First, tax revenues have been known to end up somewhere other than their intended destination.

Second, government funding also creates financial conflict of interest. As Revere-Frye, et al., wrote:

"Consider the need to control costs as an example. It could lead to a government-funded study being biased to show that the least expensive drug for a given indication is as good as a costlier alternative, or that the life-extending potential of an expensive drug is low."²⁰

This need to control costs could lead the government to reduce funding for research into potentially beneficial therapies. Without the incentive of a profit motive, the urgency to study new therapies would be diminished, potentially harming patients by delaying market introduction. The pace of research would be determined by the vagaries of governmental politics and budgeting.



Source: Dorsey, et al., "Funding of U.S. Biomedical Research, 2003-2008," JAMA, January 13, 2010

As shown above, industry funding of research has grown much faster than NIH funding.³ If government becomes the sole source of research funding, as is the case with NIH, we can expect a slowdown of essential research into new therapies.

By sharing responsibilities for clinical research, private innovators and government regulators contribute to the development of scientific advances. As mentioned earlier, government and industry have successfully collaborated to balance safety and patient access to new technologies. Consolidating both roles into a single entity would skew the equation too far in one direction, resulting in either reduced access to beneficial technologies or insufficient oversight.

The benefits of collaboration

We clearly gain a lot from the technologies that are made possible by industry funding of research. A 2006 study reported that, from 1982-2004, disability in the U.S. declined dramatically.²¹ During this time period, the proportion of disabled individuals in long-term care institutions dropped by 42.7-54.6%, depending on age group.²¹ The largest decline in disability was from musculoskeletal disorders. David Cutler, MD of Harvard separately observed a similar trend and observed:

"...most of the reduction in disability is not from people having fewer disabling conditions. Rather, reduced disability is because fewer people who have these conditions become disabled."²²

Consider total joint replacement. Between 1998 and 2008, the U.S. revision burden decreased, even as patients became younger.²³ We estimate that the direct savings to the healthcare system of avoided revisions at $2 billion.²⁴ The economic benefits of returning people to work, avoiding chronic conditions from sedentary lifestyles, and reducing the cost of long-term care are harder to quantify, but undoubtedly exceed the savings in direct costs.

These health and economic benefits would not have been possible without privately-funded research that led to the introduction of improved new therapies. Since musculoskeletal disorders are still the leading cause of disability,²⁵ more research and innovation are required. Industry is the most capable—and motivated—source of funding for that research.

Conclusion: Collaboration with private innovators is a necessity

As overly zealous politicians, academicians, and reporters stigmatize industry funding, we can expect to see qualified researchers avoid collaborations with industry. This will not benefit patients; rather, it will slow down the pace and productivity of research, and damage the credibility of medical research--the very commodity that critics of industry funding supposedly wish to nurture and protect.