Informed Consent

Assuring that adequate provisions exist for securing informed consent is a central duty of IRBs. The requirements for informed consent are specified in the federal regulations. These require that investigators ''shall seek such consent only under circumstances that provide the prospective subject . . . sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence. The information that is given to the subject . . . shall be in language that is understandable to [him]'' (39). The regulations further stipulate that ''No informed consent, whether oral or written, may include any exculpatory language through which the subject . . . is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the investigator, the sponsor, the institution or its agents from liability from negligence'' (40).

The federal regulations specify the information that shall be provided to each subject:

(1) A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental;

(2) A description of any reasonably foreseeable risks or discomforts to the subjects;

(3) A description of any benefits to the subject or to others which may reasonably be expected from research;

(4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;

(5) A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;

(6) For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;

(7) An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject; and

(8) A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled

In addition to these basic elements of informed consent, IRBs shall also require that information shall be provided, where indicated, to the effect that (a) the particular treatment or procedure being tested may involve risks to the subject that are currently unforeseeable; (b) foreseeable circumstances may exist under which continued participation by the subject may be terminated by the investigator without regard to the subject's consent; (c) additional costs to the subject may result from participation in the research; (d) the consequences of a decision to withdraw; and (e) significant findings that may influence a subject's continued participation will be related to the subject (42).

In addition to the elements enumerated in the federal regulations, IRBs must consider whether consent forms should include the fact of randomization in the case of prospective randomized clinical trials. Numerous arguments have been made for and against disclosing to prospective subjects the fact that their treatment will be selected by a randomization procedure (43).

Those who feel that the fact of randomization need not be disclosed to prospective subjects argue that since the alternative treatments to be tested are not known to produce significantly different results and since the physician would have to make an arbitrary selection of one treatment or the other for a particular patient, notification that selection of treatment is by computer rather than by the patient's own physician does not provide additional protection for the subjects and is unnecessary. The response to this contention is that a subject's ability to exercise full autonomy over what will be done with his or her own body is best served by notifying the subject as to how the treatment will be selected and by whom, even if the selection process is equally arbitrary whatever process is used.

The weight of the arguments favors the notion that for consent to be fully informed, subjects must be notified that their treatments will be allocated in a random manner, i.e., selected by a process other than the judgment of their own physician. The meaning of the concept of randomization and the fact that it will be the manner by which treatment is selected is therefore considered to be an important and integral part of informed consent for participation in randomized clinical trials.

Implicit in the elements that comprise informed consent for subjects participating in clinical trials is that subjects will be notified of the nature of their disease. Current bioethical thinking views this to be essential in order for patients/ subjects to give legally effective informed consent. The current practice in the United States is that informed consent to participate in clinical trials requires that patients be notified of their diagnosis. Accordingly, a statement regarding the diagnosis is required in consent forms for participation in clinical trials that are sponsored by national cooperative groups. It is of interest that other Western countries do not feel that it is necessary or even appropriate to inform patients of their diagnosis as part of the consent process.

The elements listed above that need be provided for consent to be informed must be expressed in a written consent form. It is evident that a consent form with all these elements will be a lengthy one. In fact, consent forms for participation in clinical trials often run to three or four single-spaced typewritten pages. However, the anecdotal experience of those involved in clinical trials is that the majority of the patients appreciate the full explanation provided in the consent forms and that these explanations do aid patients and their families significantly in determining whether to participate. Although there was widespread concern that these detailed, extensive explanations would frighten patients and reduce the incidence of participation in clinical trials by prospective subjects, there are no data indicat ing that this has occurred. Rather, the evidence appears to be that the more fully informed patient is able to participate in a clinical trial in a more meaningful way, thereby making the trial a cooperative venture between the patient/subject and the investigator. IRBs should therefore not be deterred from requiring that consent forms be truly informative and should include all of the elements described above.

Two additional questions remain regarding informed consent in clinical trials. The first question is who should prepare the consent forms. Although it may be argued that a layperson, such as a lawyer, might be able to take the information provided in the clinical trial protocol and cast it into a form that would be most readily understood by prospective subjects, it is suggested here that the investigator is in a better position to perform this task. The investigator is the one who is fully informed as to the various issues that pertain to the clinical trial. Accordingly, the investigator is potentially in the best position to express the necessary information in a manner that is comprehensible to laypersons. This requires that the investigator must be capable of explaining the issues involved in terms that are understandable to the nonphysician. IRBs should insist that, if an investigator wishes to have patients participate in clinical trials under his or her authority, he or she ought to be able to explain to prospective subjects precisely what is involved in terms that subjects can understand.

The second question is whether a physician should act in the dual capacity as physician and investigator with respect to his or her own patients. Depending on the particular circumstances, IRBs may be satisfied in allowing physicians to enlist their own patients in clinical trials in which they serve as investigators and to act as the caring physician during the trial. Alternatively, IRBs may wish to require that a knowledgeable third party, for example, another physician familiar with the disease and its treatment, or a party whose concern for the patient is without any apparent conflicts of interest, such as a close family member, participate in the recruitment process and in a monitoring capacity throughout the duration of the trial.

In most university-affiliated and community hospitals, the matter should be decided with reference to the particular clinical setting for the trial, the type of patient/subject involved, and the nature of the disease entity under study. For example, in a community hospital having no medical oncologist, cardiologist, etc., other than the physician/investigator, and where the prospective subjects are all private patients of the investigator, it may be appropriate that a patient advocate in the person of a family member or a member of the nursing service be present at the time of the consent proceeding. In a municipal hospital that is university-affiliated and has specialists on staff other than the investigator, it may be appropriate for one of the other staff members to be present at the time consent is enlisted so that the coercive elements that some deem to be inherent in such settings may be minimized. IRBs have to review each proposed clinical trial and specify conditions in which informed consent will be obtained on a case-by-case basis.

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