The investigator conducting a clinical trial has awesome medical and ethical responsibilities, some of which are in conflict. If she is both a physician and a researcher, as are most people conducting cancer clinical trials, she must reconcile her responsibility to give each individual patient the best possible treatment with her responsibility to conduct scientifically valid experiments in order to advance the boundaries of medical knowledge. Harold Y. Vanderpool, professor in the history and philosophy of medicine at the University of Texas Medical Branch at Galveston explains:

The investigators' ethical responsibility has primarily to do with their finding an ethically justified balance between the benefits of their research for patients now and in the future, against a respect for the persons and choices of the patients. They need to be responsible students of research ethics, and not see ethics as something that gets in the way of effective research.

There is this conflict of interest between patients and the people doing the research. People doing the research need to get valid data, and patients need to get the best possible treatment. Sometimes these coincide exactly, and sometimes they don't.

One of the biggest problems is the degree to which patients trust their physicians, and the degree to which physicians, failing to distinguish between the ethics of clinical practice and the ethics of research, offer "Trust me" statements. There are important degrees of trust between doctors and patients, and that's good. But if that same level of trust is there for the researcher, then the patient will assume, "Well the doctor is just here for my own health interests," when the research protocol says the doctor is there fundamentally to advance medical knowledge. Cancer patients are in a one-down psychological position. They have to trust their doctors. They want a cure. They need a cure. They dare not risk any kind of a personal distance or alienation from the physician-researcher. So they're very much inclined to do what the researcher wants and to accede to the requests of researchers.

When you're faced with, "This, that, or the other thing may happen," versus "You have cancer. It's going to kill you," which way do you go? It's not a hard decision. At least that was my feeling then.

I basically say, "No. I really want you to go home, spend a week, spend a weekend, get some more opinions about this, and think about it." You don't want anyone signing on just because they're desperate. The other problem is that people who are running clinical trials are by definition optimistic. You can't spend twenty hours a day doing this stuff and trying to push the frontier without believing at some point that it's going to help. That optimism obviously is contagious, and the patients get caught up in that. I try to objectively present what the pros and cons are. I say, "There's no guarantee that this is going to make a difference, no guarantee that you will get a response, and depending on how the trial is written, no guarantee that you'll even get the drug, if you get randomized into the placebo arm."

I think physicians need to be aware of the degree to which some cancer patients are in an almost coercive environment in the hospital. If the patient goes on protocol, the patient will get a special team, special attention, regular checking, and be part of an esprit de corps. If they don't go on protocol and their cancers are terminal, they're going to get threadbare, less enthusiastic, less professionalized care. So I think it's important that physicians not sell their protocols by saying, "Now, if you enroll in this we'll be able to give you all this attention."

Then there are the professional rewards. You're probably familiar with the phrase "publish or perish." Physician-researchers at academic medical centers are expected to publish scientific papers, and if they don't, their careers may be derailed. One sure route to publication is to conduct clinical trials. Adding to the pressure to recruit patients is the tradition in multicenter trials for the investigator who has recruited the largest number of patients to be listed as primary author of the scientific paper announcing the study's results. Therefore there's at least an indirect relationship between a physician's professional advancement and the number of patients she recruits to her clinical trials.

Please do not misunderstand: this doesn't imply that physician-researchers are crooks or con men out to shanghai innocent patients into second-rate clinical trials in order to collect a bounty of financial and professional rewards. On the contrary, the vast majority of physicians participating as investigators in clinical trials clearly conduct themselves with the highest level of personal and professional ethics. They are mindful of their potential conflicts of interest, and they take conscious steps to avoid these conflicts.

Nevertheless those conflicts are there, and as a patient you too must be conscious of them. What does this mean on an operational level? Perhaps it means that you should get a second opinion if your physician suggests you participate in a clinical trial that she's personally involved in. Perhaps it means that you should look into other therapies and clinical trials even if your physician presents a convincing case that her trial offers you the best chance. You may end up independently coming to the same conclusion, or you may find another avenue that offers even more hope.

Dr. Vanderpool talks about the responsibility of those who are supporting and sponsoring trials:

I think medical centers have the responsibility not to place monetary pressure on their researchers and their departments in such a way that institutional self-interest outweighs ethical responsibility. Sponsors should avoid placing restrictions, pressures, or temptations toward self-interest on researchers. That could compromise the rights of patients. I think the sponsors themselves should care about such pressures on the researchers, and shouldn't hype the prospects of this drug beyond an accurate reading of what they've discovered up to the point it's being used. I think they have to be honest, and they have to be aware that the pressures they might place on researchers or the rewards they might give to researchers might compromise the protections and rights of patients.

Notes

1. Stuart E. Lind, "Financial Issues and Incentives Related to Clinical Research and Innovative Therapies," in Vanderpool, The Ethics of Research, 185-202.