The Basic Requirements of Informed Consent
Madeleine M. Jester, RN, JD

Abstract

Once a product has gone through the early stages of development, it is tested for efficacy and safety on humans in controlled clinical trials. However, before a subject can be enrolled in a clinical trial, that subject must agree to participate. The agreement to participate is known as informed consent.

Obtaining informed consent before enrolling subjects in clinical trials is an extremely important risk management consideration, as well as a key element of a well run clinical trial. A study subject who has been thoroughly informed of the risks and expectations of participating is less likely to bring legal action if adverse events occur than one who has not.

There is a well-defined process required by the Food and Drug Administration (FDA) to obtain informed consent from research subjects who participate in clinical studies of drugs, medical devices and biological products regulated by that Agency (this includes most of the research done in the United States).

FDA regulations require certain elements to be included in informed consent documents. Aside from these requirements, there are a number of actions investigators can take to make sure potential study subjects receive enough information to make a truly informed decision to participate in a research study.

The Regulations

FDA regulations require certain elements to be included within the patient consent form.¹ The elements listed below in italics are the eight core requirements for informed consent. This information must be provided to each study subject. Each element is followed by additional explanatory comments.² Following the discussion on the eight core elements is a discussion on additional elements that must be provided if they are applicable to a specific study situation.

Core Elements

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.

This statement must make clear that the program in question is research, outline the procedures to be done that are part of the research, and indicate that one purpose of the study is to test the safety of the test article.

2. A description of any reasonable foreseeable risks or discomforts to the subject.

This should include discussion of not only side effects of the test article, but any discomforts to be experienced from any procedures (for example, blood tests) to be done as part of the research.

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

Any benefits to the subject should not be overstated, including making it clear that the participant may get no benefit from the research.

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

The consent form should contain enough information about other available treatments so the subject can make an informed decision about participating in the study.

5. A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained and that notes the possibility that the Food and Drug Administration may inspect the records.

It is vital that the prospective subject understand that when he or she agrees to participate in research the study records become part of the database for that clinical trial, and there is no option to keep those records from being reviewed and audited by the sponsor of the research and the FDA.

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

This information should be very clear and as specific as possible.

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.

The FDA suggests that the named contact persons be independent of the clinical study team if possible, so that the study subjects will feel free to call if they have concerns.

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

There should be no language in the consent form that would limit or penalize the subject's right to withdraw.

Additional Elements

The following additional elements must be provided to the study subject as appropriate to the specific study situation.³

1. A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable.

If test results from animals regarding possible genetic mutations or fetal malformations are not available, the consent form should state this so that study subjects can understand the potential danger of taking a drug for which animal data are not available. The significance of any available animal data should also be explained. If female study subjects should avoid becoming pregnant during a study, proper forms of birth control should be used. This should be explained as specifically as possible.

2. Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent.

These circumstances should be explained within the consent form; for example, a consent form could state that a subject may be dropped from the study for not following study procedures (for example, missing appointments).

3. Any additional costs to the subject that may result from participation in the research.

Because some reimbursement mechanisms will not reimburse study subjects for research expenses including experimental drugs, any additional costs should be clearly explained.

4. The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject.

If leaving the study before it is finished could be harmful to the subject's health, the consent form should explain this. It should also list any procedures the subject should undergo in order to safely leave the study.

5. A statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject.

There should be a plan to notify study subjects about new information that would impact on their staying in the study.

6. The approximate number of subjects involved in the study.

This information should be provided if it has a bearing on the subject's decision to participate.

Additional FDA Recommendations

This completes the listing of the basic FDA requirements that must be spelled out in the consent form itself. However, having the subject read and sign a written consent document containing these elements is only a small part of the consent process. Following are some other important factors to consider in obtaining proper consent, as summarized from the FDA regulations and guidance.

When obtaining consent, the formal written document must be used within a context that allows the subject to ask questions, and the person overseeing the process to feel satisfied that the study subject really does understand exactly what participation in the research will involve.

No study procedures, even tests to determine if a potential participant would be an appropriate candidate for a study, should be done until consent has been obtained.

The consent form itself should be written in language that is understandable (at about the sixth grade level), and technical terms used in the form should be defined. Also, no language should be included in the form that makes inappropriate claims for efficacy. Such claims could improperly influence the subject's decision to participate in the study.

Another way study subjects can be influenced to participate in clinical studies is by paying them. If subjects are to be paid the amount should be small, and only given to compensate study participants for their time and travel expenses. These payments should also not depend on the subjects finishing the study if it is not appropriate for them to do so, and the amounts and payment schedule should be described in the consent form.

Consents should be written in a style that is conversational, using phrases like "You are being asked to participate..." Phrases within the text like "You understand...", that assume full patient understanding, should be avoided. The form should only use statements that indicate the information in the document has been explained.

The FDA Guide discusses other situations that apply to non English -speaking subjects, or to those who are unable to read. If the sponsor knows that a study will be offered to a number of non English -speaking participants, the consent form can be appropriately translated ahead of time and be available in the other language. Having an interpreter present who can further explain the consent, and help to answer the potential participant's questions at the time of the signing, is important. Last minute verbal translation of a consent form should be avoided, since the subject's understanding of what participation in the study would involve could be less than complete. The Guide suggests that a short form summarizing the elements of consent could be used in such circumstances, if it is signed by the study subject, and if all the elements of informed consent discussed above are presented orally. A person who cannot read or write must have the consent document explained fully. The subject should "make his mark" on the document, and a witness who can attest to the adequacy of the process should also sign the form. ^4,5

Additional Considerations

Research subjects are a special breed. For many, this is an opportunity for them to be altruistic, and they may participate in research because they believe they are "doing something for mankind." Other research subjects may decide to participate in a study because they are very sick, or there are no other treatments available. Investigators must never forget, however, that a subject may be vulnerable, and agree to participate in a clinical study for the wrong reasons. The subject may not truly or fully appreciate that a research study is just that; research. It is not routine treatment, and should not be thought of in that context. Also, if the investigator/physician in charge of the clinical study happens to be that subject's regular health care professional, the subject may be reluctant to say no to a program that he believes is recommended by someone in a position of trust.

Conclusion

As discussed above, it is important form a risk management perspective to obtain informed consent from subjects before enrolling them in clinical trials. As an additional consideration, A study subject who has been thoroughly informed of the risks and expectations of participating in a research study is less likely to bring legal action if adverse events occur.. This is an extremely important risk management consideration as well as a key element of a well run clinical trial.

See also A History of Informed Consent; Some Exceptions to Informed Consent, A Case Study on Informed Consent

References

1. Code of Federal Regulations at 21 CFR part 50.25

2. FDA information sheet, A Guide to Informed Consent Documents, FDA web site, http://www.fda.gov ,1997

3. Supra, 1

4. Code of Federal Regulations at 21 CFR part 50.20

5. Supra, 2

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