Informed Consent and Participants’ Safety

Who/What Ensures Clinical Trial Participants’ Safety?

Most clinical research is federally regulated and has built in safeguards to protect participants’ rights and welfare:

• Researchers must follow strict ethical and scientific principles to protect patients and obtain valid results.

• Sponsors must adhere to Good Clinical Practice, an international standard for human trials that requires drug companies to obtain informed consent, have trials vetted by independent ethics committees, provide on-site monitoring, and give treatment for adverse effects both during and after trials.

• The FDA inspects clinical trial sites to “protect the rights and welfare of volunteers and verify the quality and integrity of data submitted for review.”

• Every trial follows a controlled protocol, or study plan, that explains what will be done and why (e.g. number of participants, drug dosages, medical tests to be administered, etc.) and has been approved by the study sponsor, the medical center or clinic where the work will be done.

• As a clinical trial progresses, researchers report results at scientific meetings, to medical journals, and to various government agencies.

“Between the FDA, the help of other government agencies, Institutional Review Boards, the required monitoring of studies by industry and private sponsors, and the required oversight and reporting by investigators and their staff, a lot of people are looking out for the research participant's safety." says David A. Lepay, M.D., Ph.D., director of the FDA's Good Clinical Practice Program.^[6]

Investigational New Drug Application (IND)

Before a clinical trial can begin enrolling participants, sponsors must obtain FDA approval of an (IND) application to advance to human trials. The decision is based on preclinical data showing that the product will not expose human participants to unreasonable risks in limited, early-stage clinical studies. The IND application highlights:

• “Any serious, unexpected adverse experience associated with use of the drug.”
• “Any finding from tests in laboratory animals that suggests a significant risk for including reports of mutagenicity, teratogenicity, or carcinogenicity.”
• “Any risks of particular severity or seriousness anticipated on the basis of the toxicological data in animals or prior studies in humans with the drug or related drugs.”
• “Identification of all safety reports previously filed with the IND concerning a similar adverse experience, and analyze the significance of this in light of the previous, similar reports.”
• Previous safety problems identified in other countries during the clinical trial or marketing stages, or withdrawal of the drug from market.
• “The pharmacological and toxicological effects of the drug in laboratory animals and, to the extent known, in humans, based on which the sponsor has concluded that it is reasonably safe to conduct the proposed clinical investigations. The kind, duration, and scope of animal and other tests required varies with the duration and nature of the proposed investigations.
• “… information relating to safety and efficacy in humans obtained from prior clinical studies.”
• “A description of possible risks and side effects to be anticipated on the basis of prior experience with the drug under investigation or with related drugs, and of precautions or special monitoring to be done as part of the investigational use of the drug.”

During the course of the study, sponsors must update the FDA should any new safety information become available. Sponsors may withdraw treatments from clinical trials at any stage; the FDA cannot dictate whether or not a clinical trial should continue.

Institutional Review Boards (IRBs) approve protocol

Comprised of lay people with varying backgrounds and experts, IRBs review research protocols and related materials to protect research participants’ rights and welfare, making sure they are fully informed and have given their written consent before studies begin. IRBs examine protocol to ensure that:

• It does not present an undue or unnecessary risk to the patient.
• Participants are treated humanely and ethically.
• Risks are minimal compared with potential benefits of the treatment.
• Design is consistent with sound scientific principles, ethical norms, regulatory requirements, institutional commitments and regulations, applicable law, standards of professional conduct and practice, and community attitudes.
• Informed consent document includes all required elements.
• Inclusion and exclusion criteria identify the appropriate people as eligible for the trial.

IRBs have the authority to approve, require modifications to secure approval, or disapprove research.

“It's important that we have the rapport with the public that allows them to trust us with this program,” says Bernard A. Schwetz, D.V.M., Ph.D., acting director of the Office for Human Research Protections in the Department of Health and Human Services. “Without people willing to participate, there won't be any clinical trials.”

Informed consent process

The FDA requires that potential clinical trial participants receive, and review at their leisure, all relevant study information before deciding whether or not to enroll. The written information must be understandable to every participant, and should include details about the trial’s purpose, duration, procedures, potential risks and benefits, and alternative therapies, as well as key contacts and the rights of study participants.

The informed consent process allows the researcher and patient to exchange information and ask questions. Patients invited to enter a trial are not obligated to join, but can consent to participate if they find the potential risks and benefits acceptable. Participants must sign a consent form prior to enrollment and before any study procedures can be performed. Consent is entirely voluntary, and participants can leave a study at any time, without penalty. Researchers may terminate participation without participants’ consent if a trial is not working or if an unexpected change occurs in the health status of a participant.

 

Sources

1. The Center for Information and Study on Clinical Research Participation (CISCRP); Results of the New National Survey of Public Perception, conducted in December 2004
2. The Center for Information and Study on Clinical Research Participation (CISCRP); Results of the New National Survey of Public Perception, conducted in December 2004
3. National Survey Shows that two-thirds of Americans Think that Clinical Research Studies are Safe ; CISCRP press release 12/23/04
4. Activa Therapy New Hope for Parkinson’s Program Clinical Trials — The Pursuit of Science [12/09; item no longer online]
5. FDA Guidance for Industry – PreMarketing Risk Assessment  
6. Clinical testing with Humans, by Carol Rados. NurseTown.com, Jobs for Healthcare Professionals [12/09; item no longer online]
7. National Coalition for PKU & Allied Disorders, Human Subjects Research Protection [12/09; item no longer online]