Trials of new cancer therapy are as well known among Norwegians as among Americans. Generally, we have also had similar ethical issues: whether seriously ill patients ought to be randomized into placebo-controlled studies, whether re-searchers ought to inform patients thoroughly about alternatives to trial therapies (such as non-treatment or mere palliative care), whether researchers should have follow-up responsibilities for pa-tients, including for non-medical services (such as social services and hospice), and so on. While Fay Sawyier's case illustrates issues common to our two countries, it may also bring out some important differences.

Tempting offers
The eagerness of researchers to enroll patients in trials is well known. New trials can be interesting. They can further careers. But they cannot be carried out without a certain number of patients. Without that number to serve as research subjects, the study must be postponed or abandoned. Researchers therefore have a tendency to jump at any patient fitting the criteria for inclusion in their study.

Though eagerness is a virtue in researchers, it does have a downside. It tends to infect patients, making their "consent" resemble a spontaneous outburst of hope (someone will help me!) more than an informed decision to participate.

I cannot say that the ritual of consent that Sawyier described does not have its counterpart in Norway. An ethics committee only reviews the consent form and accompanying written information before the trial begins. The committee cannot monitor how consent is actually obtained. Nonetheless, the ritual Sawyier described is ethically unacceptable.

In Norway, we have tried to buttress the requirements for informed consent by strongly recommending that patients have at least twenty-four hours to consider participation in a trial on the basis of written information. We stress that the information is to help the patient decide wisely, not to help the sponsor limit legal liability. So, for example, we discourage listing every recorded side effect. That's excessive. Saw-yier was surprised at the amount of "negative information" the consent document contained because the information did not seem designed to help her decide whether to participate. (To see our guidelines, in English as well as Norwegian, visit on our web site: www.etikkom.no.)

But no formal precaution, not even the twenty-four hour "cooling off" period, can prevent the consent procedure from becoming a mere ritual. Only the researchers themselves can do that.

Cut off
Next, I would like to address the decision to end the research subject's participation in treatment when the tumor, though shrinking, did not shrink enough to satisfy the research protocol. What I say here about the protocol depends on the description Sawyier has given of it. I have not studied the protocol itself.

Given Sawyier's description, I am pretty sure the protocol would not be approved in Norway. We do not, of course, require researchers to keep a patient in a trial when she falls short of the criteria for inclusion. But we would not approve a protocol unless the research sponsor agreed to continue treatment for research subjects who, though disqualified by the protocol, still show significant benefit from the experimental treatment. Our guide- lines stress the responsibility of follow-up, access to treatment, and plans for preparing researchers to respond to related medical problems, especially when subjects are from vulnerable groups, such as seriously ill cancer patients. If sponsors (or researchers) are not willing to take on this responsibility, they cannot do the research.

Physician or mere researcher?
Another disturbing issue in this case is the unresponsiveness of the researcher -- who is also a physician -- to a patient for whom being dropped from the study seems a death sentence. The physician should have done more, much more, for her patient. I earlier stressed the importance of medical follow-up for every individual patient included in the trial. Equally important in this case is the physician's duty to act as a physician, not only as a researcher, even when the patient is a "mere" re- research subject.

The ethics committee does not evaluate the moral virtues of researchers, but health-care institutions that do research with patients should consider such evaluation a vital part of its quality assurance. If I were asked about an unresponsive researcher like this in Norway, I would recommend a transfer to a laboratory where there would be no direct contact with patients. Patients need a caring and empathic physician.

The researcher in this case reenforced the stereotype of the aloof, one-sided, and uncaring re-searcher. In the long run, such researchers damage the fragile confidence that even they rely on to attract subjects. Much of the willingness of people to become subjects of medical research is their assumption - and hope - that the physician-researcher will act as their physician during the research -- that, at the very least, the physician will take the patient's interests seriously enough to offer the best available therapy. Cold and disinterested physicians should do patients the favor of finding something else to do.

Clout
Sawyier reports that, in desperation, her husband called the medical director of the sponsoring pharmaceutical company to get her back in treatment. That call seems to have worked. Sawyier was soon "taken over" by another oncologist who, undoubtedly, had been prompted by the director. That was good for this patient.

But, as Sawyier makes clear, this exercise of "clout" -- her husband's status coupled, no doubt, with the company's fear of bad publicity -- is morally disturbing: what about all the other vulnerable patients that do not have a husband who is a lawyer?

Using clout to be heard is unfair, but still common even in Norway, with its "socialized medicine" (as we are happy to call it). It is, of course, true that using clout is a natural human response in such desperate circumstances. Anyone who would not have availed him- self of it under the circumstances would have seemed less than human. The husband's phone call is in itself understandable, even honorable, certainly not blamable.

What is blamable is that the company would only make an exception for a patient who had clout - but not for all the other patients who were in the same position as she was. Fairness is an important part of research ethics; researchers should at least try to treat relevantly similar cases alike.

One can of course speculate on the motives of the company. I will not, except to say that I would be disappointed if the company's medical director thought primarily of the reputation of the company before calling the researchers. Pharmaceutical companies have long worked with medical authorities to develop international guidelines for good clinical practice (often abbreviated ICH-GCP). These establish an international standard of acceptable scientific and ethical practice. They have a whole chapter on research ethics. I would like to think that the phone call reminded the medical director that cutting a patient off of an effective treatment is not in accord with international standards.

Independent Review
What Sawyier's case shows is that an independent review is necessary in clinical trials, to assure fairness to all subjects and, especially, to protect the most vulnerable ones. Ethics committees are supposed to provide that independent review. In this case, the ethics committee seems to have failed (as ethics committees sometimes do). The failure suggests the importance of another kind of review, such as a patient advocate might provide. But will those most in need of independent review know how to access such an advocate any more than they know how to access the ethics committee? "I have only cancer, not Alzheimer's" is no joke.