As a suggested followup to this topic, a simple recitation of some of most egregious violations of the The Nuremberg Code and Declaration of Helinski in pharma-sponsored clinical research, over the last two decades, might be instructive, especially to new physicians contemplating careers in the pharmaceutical industry. The list is lengthy. It’s a veritable rogue’s gallery.

“Federal regulation should require that training about the nature of conflicts of interest, their potential for harm, and the ways that conflicts can be managed, reduced, or eliminated should be mandatory for all investigators who conduct clinical research within and outside of academic medical centers. For physician-investigators outside of academic medicine, training should also cover key elements of research: the importance of inclusion and exclusion criteria and informed consent, the ethical and scientific issues posed by particular research methods such as double blind placebo-controlled studies, and their obligations as an investigator as compared with those of a treating physician.”

As well, training programs for academic physician-investigators should include information on their obligations as a treating physician as compared with those of an investigator.

“When investigators have financial interests in the outcome of the research or stand to gain substantially from conducting a clinical trial, it may affect their judgment throughout the conduct of the trial, including the many judgments that must be made during the process of enrolling and recruiting individuals to participate as research subjects. Potential participants can be harmed by recruitment practices that insufficiently inform them of the risks of the study, ignore medical conditions that place them at risk in the trial, or encourage them to discontinue or forego a treatment regimen likely to be better for them than the regimen being evaluated in the trial.”

Research participants may question the motives of a physician-investigator who appears in advertisements for products he evaluated in clinical trials.

http://tinyurl.com/yhz5cve

Do the pharma sponsors routinely grant exceptions, exemptions, and special dispensation for research protocol violations reported by the principal investigator, as a means of increasing enrollment?

Do the pharma research sponsors routinely award additional research studies to the principal investigator and the academic institution as incentives to increase study enrollment?

Does the net effect of indirect transfers of value and surrogates (e.g., IRBs and CROs) lessen risk of liability or culpability to pharma for fraudulent research studies?

To Pharmavet: is the true incidence of screening failures ALWAYS reported? if so, to whom? do the pharma sponsors ALWAYS pay the investigator for screening failures? does Medicare/Medicaid/Tricare routinely pay for screening failures? do these insurers EVER pay for screening failures? If so, is it routinely disclosed to the insurer that patient was being screened for research study? Are formal informed consents for study participation obtained PRIOR to screening for study participation? Or are formal informed consents for study participation obtained AFTER repeating the screening procedures? In your experience, how exactly did the pharma sponsors “incentivize” faster study enrollment?

Thanks for the fascinating insight into the real world of clinical trials. Amazing.

Can you provide some more detail about rule #4? From what we’ve all been reading lately, the distinction between researchers and speakers has been pretty blurry. How commonly is this rule applied? And to what degree would the industry person in charge of the trial have any say over who the marketing and/or education people could use as speakers?

Best,

Larry

1) It is standard procedure when doing a pre-study visit to ask the Principal Investigator (PI) how many other studies they are doing so as to assess their capability to do my study. They know that they can get away with a low number because we have no legal means of verification. After the study starts, the enrollment is slow, and you find out from the coordinator that the PI is really doing a ton of studies in your disease states, you resort to “incentivizing” the PI per the white paper to give your study priority, thus starts the slippery slop.

2) Some investigators have huge screen failure rates while actually completing few patients. If payments for screen failures are not capped (I used to cap them at 15% of the total budget), a PI can make a lot of money just from screen failures. If the PI exceeds the cap, then he/she has to eat the cost.

3) I never pay the full salary for nurses or other support staff, although surprisingly many companies do. With multiple companies paying full salaries it is easy to see how PI’s can pull in a lot of money.

4) One simple rule. If I use a physician as a PI I don’t use him as a speaker, and vice verse. This reduces conflict of interest.

5) When most studies were done in academia, it was typical to pay 40-60% in overhead to the university as the fee to get in the door. In non-university settings, I offer no overhead at first, and most of the time pay 10-15% if anything.

6) Train the CRO’s to be tough negotiators with PI’s. Since it’s not their money they don’t see it as their role. Once I, as a sponsor begin to deny CRO change orders for more funds to the PI they begin to see the picture more clearly.

7) I used competitive enrollment, but didn’t reward it with a bonus to the PI. It was always something like sending a coordinator to an educational meeting, which the sponsor paid for directly.

Just a few thoughts.