Informed Consent

Informed_consentParticipating in a clinical trial: The diversity observed in society, by consensus, should be reflected in clinical trials through the appropriate inclusion of ethnic minority populations. Patient Recruitment plays a significant role in the activities and responsibilities of sites conducting clinical trials. IRBs must review all final copies of materials investigators propose to use to recruit subject to assure does not promise or imply a certainty of cure or other benefit beyond what is contained in the protocol and the informed consent document. This is especially critical when a study may involve subjects who are likely to be vulnerable to undue influence. [21 CFR 50.20, 50.25, 56.111(a)(3), 56.111(b) and 812.20(b)(11).] No claims should be made, either explicitly or implicitly, that the drug, biologic or device is safe or effective for the purposes under investigation, or that the test article is known to be equivalent or superior to any other drug, biologic or device. Such representation would not only be misleading to subjects but would also be a violation of the Agency’s regulations concerning the promotion of investigational drugs [21 CFR 312.7(a)] and of investigational devices [21 CFR 812.7(d)]. Advertising for recruitment into investigational drug, biologic or device studies should not use terms such as “new treatment,” “new medication” or “new drug” without explaining that the test article is investigational, so as not to leads study subjects to believe they will be receiving newly improved products of proven worth. Advertisements should not promise “free medical treatment,” when the intent is only to say subjects will not be charged for taking part in the investigation. Advertisements may state that subjects will be paid, but should not emphasize the payment or the amount to be paid, by such means as larger or bold type. Generally, FDA believes that any advertisement to recruit subjects should be limited to the information the prospective subjects need to determine their eligibility and interest.

Informed Consent: Informed consent is reviewed by the IRB. It is a process through which you learn details about the trial before deciding whether to take part. This includes learning about the trial’s purpose and possible risks and benefits. This is a critical part of ensuring patient safety in research. Including the trial’s: Purpose, Procedures, Risks and benefits. Also includes: right to: Make a decision about participating, Leave the study at any time. Also before agreeing to take part the right to: Learn about all your treatment options, Learn all that is involved in the trial, including all details about treatment, tests, and possible risks and benefits. Discuss the trial with the principal investigator and other members of the research team, Both hear and read the information in language you can understand. FDA regulations and ICH guidelines both require “the information that is given to the subject or the representative shall be in language understandable to the subject or the representative.” If the participant’s native language is not English, the sponsor must translate the informed consent into the language of the participant.

  • Children’s AssentChildren are not able to give true informed consent, so they are asked for their assent to take part (or dissent from taking part) in a clinical trial. Before they can assent, the trial must be explained in age-appropriate language or using visual aids. In addition, parents or guardians are asked to give permission for their child to take part in a trial. Assent must be obtained from children unless: , The child is not capable of assenting, The clinical trial offers a treatment or procedure that is thought to be better than those currently available, The clinical trial offers the only option. Even in these cases, permission from the parent or guardian is required.

Locating trials: Depending on the kind of participants required, sponsors of clinical trials, or contract research organizations working on their behalf, try to find sites with qualified personnel as well as access to patients who could participate in the trial. Working with those sites, they may use various recruitment strategies, including patient databases, and personal recruitment of patients by investigators. Volunteers with specific conditions or diseases have additional online resources to help them locate clinical trials. Volunteers may search directly on ClinicalTrials.gov to locate trials using a registry run by the US NIH and National Laboratory of Medicine. However, many clinical trials will not accept participants who contact them directly to volunteer, as it is believed this may bias the characteristics of the population being studied. Such trials typically recruit via networks of medical professionals who ask their individual patients to consider enrollment. Other sites include: nhlbi.nih.gov/studies/index.htm and researchmatch.org

Compensation: The IRB should determine that the risks to subjects are reasonable in relation to anticipated benefits [21 CFR 56.111(a)(2)] and that the consent document contains an adequate description of the study procedures [21 CFR 50.25(a)(1)] as well as the risks [21 CFR 50.25(a)(2)] and benefits [21 CFR 50.25(a)(3)]. It is not uncommon for subjects to be paid for their participation in research, especially in the early phases of investigational drug, biologic or device development. Payment to research subjects for participation in studies is not considered a benefit, it is a recruitment incentive. Financial incentives are often used when health benefits to subjects are remote or non-existent. The amount and schedule of all payments should be presented to the IRB at the time of initial review. The IRB should review both the amount of payment and the proposed method and timing of disbursement to assure that neither are coercive or present undue influence [21 CFR 50.20].

Any credit for payment should accrue as the study progresses and not be contingent upon the subject completing the entire study. Unless it creates undue inconvenience or a coercive practice, payment to subjects who withdraw from the study may be made at the time they would have completed the study (or completed a phase of the study) had they not withdrawn. While the entire payment should not be contingent upon completion of the entire study, payment of a small proportion as an incentive for completion of the study is acceptable to FDA, providing that such incentive is not coercive. The IRB should determine that the amount paid as a bonus for completion is reasonable and not so large as to unduly induce subjects to stay in the study when they would otherwise have withdrawn. All information concerning payment, including the amount and schedule of payment(s), should be set forth in the informed consent document.

Screening Tests: For some studies, the use of screening tests to assess whether prospective subjects are appropriate candidates for inclusion in studies is an appropriate pre-entry activity. While an investigator may discuss availability of studies and the possibility of entry into a study with a prospective subject without first obtaining consent, informed consent must be obtained prior to initiation of any clinical procedures that are performed solely for the purpose of determining eligibility for research, including withdrawal from medication (wash-out). When wash-out is done in anticipation of or in preparation for the research, it is part of the research. Procedures that are to be performed as part of the practice of medicine and which would be done whether or not study entry was contemplated, such as for diagnosis or treatment of a disease or medical condition, may be performed and the results subsequently used for determining study eligibility without first obtaining consent. On the other hand, informed consent must be obtained prior to initiation of any clinical screening procedures that is performed solely for the purpose of determining eligibility for research. When a doctor-patient relationship exists, prospective subjects may not realize that clinical tests performed solely for determining eligibility for research enrollment are not required for their medical care. Physician-investigators should take extra care to clarify with their patient-subjects why certain tests are being conducted. Clinical screening procedures for research eligibility are considered part of the subject selection and recruitment process and, therefore, require IRB oversight. If the screening qualifies as a minimal risk procedure [21 CFR 56.102(i)], the IRB may choose to use expedited review procedures [21 CFR 56.110]. The IRB should receive a written outline of the screening procedure to be followed and how consent for screening will be obtained. The IRB may find it appropriate to limit the scope of the screening consent to a description of the screening tests and to the reasons for performing the tests including a brief summary description of the study in which they may be asked to participate. Unless the screening tests involve more than minimal risk or involve a procedure for which written consent is normally required outside the research context, the IRB may decide that prospective study subjects need not sign a consent document [21 CFR 56.109(c)]. If the screening indicates that the prospective subject is eligible, the informed consent procedures for the study, as approved by the IRB, would then be followed. Certain clinical tests, such as for HIV infection, may have State requirements regarding (1) the information that must be provided to the participant, (2) which organizations have access to the test results and (3) whether a positive result has to be reported to the health department. Prospective subjects should be informed of any such requirements and how an unfavorable test result could affect employment or insurance before the test is conducted. The IRB may wish to confirm that such tests are required by the protocol of the study and retention plan for any biological samples.

Benefits vs Risks: Before a new drug or biologic can be marketed, its sponsor must show, through adequate and well-controlled clinical studies, that it is effective. A well-controlled study permits a comparison of subjects treated with the new agent with a suitable control population, so that the effect of the new agent can be determined and distinguished from other influences, such as spontaneous change, “placebo” effects, concomitant therapy, or observer expectations. FDA regulations [21 CFR 314.126] cite five different kinds of controls that can be useful in particular circumstances.

  • Possible Benefits: Taking part in a clinical trial can have many benefits. For example, gaining access to new treatments before they’re widely available. If a new treatment is proven to work, the benefit. In late-phase clinical trials, possible benefits or risks of a treatment can be identified earlier than they would be in general medical practice. This is because late-phase trials have large groups of similar patients taking the same treatment the same way. These patients are closely watched by Data and Safety Monitoring Boards. Even if you don’t directly benefit from the results of the clinical trial you take part in, the information gathered can help others and add to scientific knowledge. People who take part in clinical trials are vital to the process of improving medical care. Many people volunteer because they want to help others.
  • Possible Risks: The new strategies and treatments being studied aren’t always better than current standard care. Even if a new approach benefits some participants, it may not work for all. A new treatment may have side effects or risks that doctors don’t know about or expect. This is especially true during phase I and phase II clinical trials. The risk of side effects might be even greater for trials with cutting-edge approaches, such as gene therapy or new biological treatments. Health insurance and health care providers don’t always cover all patient care costs for clinical trials.