||Dr. Arthur Caplan, chair of Penn’s department of medical ethics, spoke recently at a Grand Rounds session on conflict of interest.
DiFronzo is a project officer for the Blood and Marrow Transplant Clinical Trials Network, which sponsors clinical trials in non-NIH institutions. She reviewed the facts of the case for rounds.
“Let’s call it the Wonder Study,” she said. “It was to be conducted at 35 clinical sites around the country.”
As a randomized phase III drug trial, the primary
objective was “to determine whether the Wonder Drug improves overall survival for patients receiving a stem cell transplant for the treatment of their hematological malignancy.”
The drug was previously tested in a phase I trial, which evaluates safety in humans, and phase II clinical trials, which measure therapeutic efficacy.
Based on encouraging findings from these studies, the drug was selected for further evaluation.
Now on the cusp of phase III, it would compare the drug’s results with standard treatments
in a relatively large group of patients whose malignancies had previously failed multiple
But there was a problem. “One of the sites,” DiFronzo said, “revealed that the institution and one of the co-investigators were partial owners of a patent related to a drug used in the study.”
NIH policy states that extramural institutions participating in NIH-funded studies must have policies for disclosing and managing CoI. But NIH (as of this Apr. 2 session of rounds) hadn’t specified how their conflicts should be managed or disclosed.
This was an extramural study and DiFronzo turned to the Bioethics Consultation Service for advice.
The scientist/patent-owner—“Let’s call him Dr. No,” said DiFronzo—had not designed the study, nor would he be involved in data analysis. Yet he planned to make referrals, so he might be involved in obtaining patients’ informed consent.
Meanwhile, the network data coordinating center,
which reviews materials for studies and manages the clinical trials, noted that the consent
included a section titled “Who could benefit
financially from the study?”
This portion explained that both Dr. No’s institution
and Dr. No had partial ownership of the patent. But DiFronzo still needed to know:
- Is it appropriate for a patent holder to be a co-investigator?
- If so, is disclosure in the consent form sufficient
for managing the conflict?
- Is it appropriate for a co-investigator who partially
owns patents to refer patients for enrollment
in the trial? Or to obtain informed consent
for the trial?
In his response, Caplan, chair of Penn’s department
of medical ethics and director of the Center
for Bioethics, defined CoI as:
- Any factor, interest or incentive that diverts a physician or scientist from his/her primary duty.
- Any factor or incentive that negatively impacts expected impartiality.
When we look at this case, he said, we’re asking:
“Are there going to be diversions—because of patents and ownership interests—from the duty to protect subjects and generate new knowledge?
“I think [scientists with an equity or patent interest] can be involved in the design of the study,” he said. “In some situations they have to be because no one else [understands] what the technology is.”
Should they assess the results?
“No,” Caplan said. “There we do have the perception,
if not the reality, that financial interest
may distort your role in trying to protect the subject...I think you do need an independent assessment.”
Can the individual be involved in subject recruitment
and can his patients then be referred?
“His patients have every right to be referred,” Caplan said. “It is unjust and unfair to exclude them...Yet somebody else on the site should be doing the recruitment just to keep the roles clear...some kind of informed consent advisor who is not paid just to recruit subjects.”
During Q&A, Caplan suggested modernizing
the consent process with modules that are image-oriented and interactive, accompanied by patient quizzes to assess comprehension.
To stay abreast of NIH-wide policy on conflict of interest, visit http://grants.nih.gov/grants/policy/coi/index.htm.