Conflict Of Interest Is A Complex Issue

Robert McKinnon Califf, MD and Harlan M. Krumholz, MD, SM

In a recent editorial in the Journal of the American College of Cardiology, Robert Califf discusses a few of the many complex questions related to the conflict of interest issue. Here CardioExchange’s Harlan Krumholz further explores the issue with Califf.

CardioExchange: Do you think that conflict of interest issues are mostly an issue about optics and not substance – or are you concerned that relationships with funders sometimes influence the science in ways that are not favorable to society?

Califf: I believe that financial conflict of interest has real substance, but that focusing exclusively on the medical products industry and failing to consider other sources of conflict of interest is a huge mistake and leads to sensationalism that then engenders reactive rules that add to bureaucracy rather than addressing the real issues. Yes, relationships with funders (medical products industry, NIH, foundations) have a huge influence on science as do professional rivalries, egos and desire to appear in the press (fame).

CardioExchange: One concern is that many trials are not under the control of the principal investigator– do you think that the profession should insist on trials that are not under the control of the funder?

Califf: I do not believe that a human experiment should be “under the control” of any single individual. Every aspect of a clinical trial is a compromise and no one gets everything they want. In fact a despotic, egotistical principal investigator can be just as dangerous as a controlling funding organization. Like our constitution, trials need a balance of power: PI, executive committee, steering committee, investigators, DMC, regulators, funders—all have a role to play. Yes, the PI ultimately is responsible, just as Hillary Clinton and Barack Obama were responsible for the security of our embassies—but there are many players. People understand this, and we should think of trials the same way. Indeed, one of the biggest influences on trials will now be the participants themselves,who are rightly becoming invovled in design, conduct and interpretation of trials.

CardioExchange: Even when the trial is not under the control of the funder, there may be other types of control. Should the PI and investigators always have full control of the data?

Califf: For now, I believe the sponsor and the trialists should both have the data under a set of rules agreed to before the trial starts. The biggest issue here is that most academic institutions are incapable of correctly managing complex trial data or analyzing it, so the PI’s are dependent on analyses from the sponsor or a CRO (clinical research organization) hired by the sponsor. I DO BELIEVE THAT INVESTIGATORS SHOULD ANALYZE THE DATA INDEPENDENTLY WITH ACCESS TO THE FULL DATA SET.

CardioExchange: What is the best path forward with conflict of interest, assuming that disclosure is not enough (since it is hard to interpret)?

Califf: The best path forward is transparency and public access to the data so that many people can analyze and interpret. This will take time. Importantly, my interpretation of the available information is that:

Academic analyses have more major errors and are not as reproducible as industry analyses. The oversight and punishment of bad behavior by FDA is important.
Bias in choosing the question is a much bigger issue than lying about the data.
In industry-sponsored trials, lying about the data is rare. Lying by omission (not looking at aspects of the data) is much more common