Fay Sawyier’s account of her experience in an early phase of the clinical trial of a new cancer treatment reflects a frequent debate in medical research, a debate setting the consumer against a more powerful adversary, the academic or pharmaceutical research investigator, whether physician or scientist. Such investigators require a human population to determine whether an unproven treatment produces the desired effect and what undesirable "side effects" there may be. Generally, a standardized clinical trial, that is, an experiment that properly monitors outcomes in patients while controlling for extraneous factors, is necessary for the Food and Drug Administration (FDA) to approve of a new drug. Without a clinical trial, a new treatment will not be fully recognized as having the appropriate and safe attributes needed to be designated a therapeutic agent for the corresponding illness. Without that recognition, ordinary physicians will not use the medication and insurance policies will not pay for their use.

Purpose
But what about Fay Sawyier? While the FDA tries to protect the U.S. consumer from unsafe treatments, patients like Sawyier who seek access to experimental or alternative therapies often discover that their individual needs are passed over to maintain the integrity of clinical trials. The immediate survival of one seems to clash with the ‘greater good,’ potential knowledge about the ability of a particular treatment to save lives or to cause significant, possibly lethal, harm. To Fay Sawyier, this clash came as a surprise when she learned that she would not continue to receive treatment because the research protocol established did not allow it.

Sawyier's case highlights four hard questions related to clinical investigation of experimental treatment, and the patients who have exhausted known remedies. First, how are patients almost without hope to be brought into the trial (especially, how is their consent to be obtained)? Second, at what point does a “clinical trial” cease to be a clinical trial, and become ordinary medical treatment? Third, can we differentiate the role of research subject from that of patient in a clinical trial? And last, can the welfare of a single patient enrolled in a clinical trial and the welfare of the larger population of patients who might benefit from what is learned from it coexist under the umbrella of the clinical trial? Underlying these four questions are two others: First, why should a patient consider participation in early phase trials? And, second, how can medical decision making be carried on as part of the clinical trial process?

Informed Consent
A common complaint of many patients participating in medical research is directed at the informed consent procedure. An institution hosting research on human subjects will have one or more review boards to provide strict guidance for principal investigators. Before investigators can begin recruiting research subjects, they must develop a clear, understandable, and thorough consent form explaining all aspects of the research to the patient.

The clinical trial Sawyier participated in had such a consent form. At the time Sawyier signed the form, she (and her family) were rightfully more concerned with seeking a means to extend her life than with specific details in the form. With death seemingly imminent, she had little choice but to sign the carefully crafted form. Signing satisfied patient, family, and researcher.

Nonetheless, investigators using the method of clinical trials should understand that the moment when a patient becomes a research subject is a sensitive one. Do the patient and family truly hear what is being said? Do they understand the benefits, risks, and procedures involved? For Fay Sawyier, the answer seems to have been no. Patient-researcher communication was inadequate.

While many investigators may go beyond what would be expected to inform their subjects, unfortunately, much of the burden of gaining information generally falls on the subjects and their families. It is apparent that significant miscommunication occurred between the clinical trial investigators and Sawyier, especially concerning the patient’s basic understanding of her path through the trial. The consequences of that misunderstanding were undone only through the resourcefulness of the patient and her family.

Few other patients have such resources. In fact, many individuals accessing health services in the United States are not even functionally literate with regards to their health care. Many also have inadequate social support or face considerable barriers to access to community resources (for example, because they lack health insurance). Taking into consideration these factors among others, it is not enough to tell patient (and family) considering enrolling in clinical trials to become an informed consumer before enrolling. It is also not enough to ask the terminal or chronically ill patient to reflect on her own motivation for participating in a clinical trial (altruism or self-preservation). While both of these steps are needed, researchers should also consider their role in protecting those individuals participating in the study.

No Promises
In an early phase clinical trial, investigators cannot assume that the treatment will have the desired effect or that there will be no serious but unexpected side-effects. Finding out about such effects is, in fact, the whole purpose of the trial. Because the treatment may or may not prove to be a good one, giving a control group (say, half the patients enrolled in the study) a placebo or alternative treatment is considered ethical. Researchers must control whatever factors could influence the relationship between the intervention (in Sawyier's case, the chemotherapeutic agent for cancer treatment) and the measured outcome (change in tumor size). They must ensure that the study will be robust and credible.

But when a patient, such as Sawyier, shows marked signs of improvement along the lines desired for the treatment, what should happen? Should the researcher acknowledge the effectiveness of the treatment and better treat their patient accordingly? But what about the study? It is certainly possible that further investigation will reveal side effects from the intervention, or that a reduction in tumor size is not the result of the treatment under study but of several other factors.

Yet once a therapeutic benefit has been detected, the somewhat “exploratory” clinical trial changes for both subject and researcher. The clinical investigator has an ethical obligation to note the benefit, and as in Fay Sawyier's case, to reconsider treatment options for the patient -- with ample assistance from patient and advocates on her behalf. The clinical researcher must constantly keep in mind the welfare of each individual enrolled in the trial as a patient, but also strive to preserve the rigor of the design and conduct of the trial.

Fay Sawyier appears to have successfully made the research investigators understand her needs as a patient. While the process of making them understand seems to have been excessively difficult, frustrating, and complicated, the lesson her success teaches is a simple one, to be observed by both patient and researcher: communicate. Patients and families considering participation in early phase clinical trials need to seek out as much information as possible. They should direct questions not only to the researchers conducting the clinical trial, but also to physicians, psychologists, social workers, nurses, case managers, and other health professions, especially some not affiliated with the study. Open communication between an informed consumer and the researchers reduces the potential for confusion and misinformation.

Caveat
The clinical investigator cannot expect to have a research sample full of Fay Sawyiers, subjects who will assert themselves and advocate for their own needs. Many patients take a submissive role in the presence of a physician or research investigator whom they identify as an “expert,” especially in a field as difficult to understand as cancer treatment. Such patients are more likely not to ask questions or seek out information from the investigator or health-care provider. Researchers need to improve upon their existing efforts to recruit subjects for clinical trials to do a better job of helping individuals considering participation gain adequate knowledge of what it means to be a subject in a clinical trial. The overall objective of research using clinical trials is to improve the health of those diagnosed with cancer. But that objetive, however good, can and should, be pursued without devaluing individual patients.