The Value of Controlled Clinical Trials; Ethical and Participant Safety Issues, 8/2000

In the not-too-distant past, there were usually two bases for a clinician choosing a specific treatment: the clinician's own experience which served as the basis for introducing a method of clinical care; or a traditional method based on the accumulation of many person's past experiences. On many occasions, good judgement worked (e.g. surgical removal of an inflamed appendix); on too many other occasions, good judgement failed (e.g. psychotherapy as the principle treatment for stomach ulcers).

In more recent years, the government (e.g. the FDA), the clinical community, third party payers and the public have demanded that proposed new therapies be thoroughly evaluated for safety and usefulness before they are made part of "accepted treatment". This has been labeled "evidence based medicine". Interestingly, the same pressures for in-depth evaluations are usually not required for older treatments -- at least not until something dramatic occurs.

The issue is what is acceptable evidence? A clinician or group of clinicians describing what they have observed is not evidence of safety or usefulness; a patient or group of patients describing what they have experienced is also not acceptable evidence of safety or usefulness. Both are evidence that an intervention may be of sufficient value to have it evaluated. To put it another way, experience is a good basis for identifying the question; however, it is not the answer to the question.

For example: in the past, there have been innumerable claims for revolutionary treatments for cerebral palsy or for the disabilities associated with it. After several years of experience with them, many have been discarded by clinicians and patients. Similarly, at the present time there are a number of new interventions being heralded as "breakthroughs" in the treatment of disabilities associated with developmental brain damage. The evidence offered in their support is the enthusiasm and experience of their advocates. Is this acceptable evidence? No, it is not.

The methodology of the controlled clinical trial has been developed as the scientific approach to evaluate the safety and usefulness of proposed new interventions. Controlled clinical trials have exacting methodologies at the conclusion of which we usually know the answers: Is it safe? Does it work? If so, for whom? If so, for how long?

Both the planning and operation of clinical trials are very hard work. Their conduct is very time-consuming for both the participants and clinicians involved. Their costs are often high. However, they are the most solid and in the long run, the fastest method for getting the needed answers. A collection of individual experiences of patients and clinicians has been shown over and over and over again not to be satisfactory. Again, these experiences serve to pose the question; a controlled clinical trial answers it.

However, several ethical problems have arisen in conduct of clinical trials. Two important ones are: informed consent and clinical responsibility.

Informed consent requires that a subject in a clinical trial (or his/her guardian) be fully informed about the questions being tested; the background which led to deciding to do the trial; the present information available about the intervention; it's supposed safety and its potential usefulness; the procedures that will be used during the trial; and any possible dangers associated with the trial. Thus, the person participating in the trial must be informed; must be knowledgeable; and must be able to make a meaningful decision about whether to participate. The person must be an active participant in the trial, not a passive subject relying upon the good intentions of the investigator.

The second issue is that of clinical responsibility. Sometimes it is very difficult to accomplish, but the clinician responsible for the patient's welfare usually should not also be the investigator in charge of the trial. Like anyone else, the investigator is enthusiastic about what he/she is doing and his/her clinical care judgement may unknowingly be compromised. The clinician in charge of the patient's care should have the patient's needs as his/her primary responsibility, not the conduct of the trial. Some of the problems we are reading about in the conduct of gene therapy trials would not have occurred if this separation of responsibility had been established. Someone needs to be responsible for the patient's welfare; someone else needs to be responsible for the conduct of the trial. All parties certainly need to work together, but with clearly distinct responsibilities.

In Summary:
Controlled clinical trials are essential to evaluate the safety and usefulness of new approaches (and old approaches) to improve the health and function of persons with cerebral palsy. Enthusiastic reports of individual experiences are not a useful substitute. Experience has established and required groundrules to make certain that the persons participating in a trial are completely informed about all of its details; also, that the personal welfare of the persons participating is always the principle concern of the clinicians involved. The Foundation is heavily involved in stimulating the organization of needed trials, but also in monitoring the manner in which they are conducted.