Questions Before Signing Clinical Trial Consent

People talk about "signing the consent" as if the document were the event. It is not. The U.S. Food and Drug Administration (FDA) describes informed consent as "an ongoing exchange of information throughout a subject's participation." The National Cancer Institute (NCI) says the form "is part of the informed consent process. This process protects your rights."

That matters. Questions you ask a week after signing are still part of consent.

Federal rules now force consent forms to lead with the decision. Under 45 CFR 46.116, "informed consent must begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject or legally authorized representative in understanding the reasons why one might or might not want to participate in the research."

Read that section first. If you still cannot say why someone might decline this trial, the section has not done its job. Say so.

The same rule requires that everything be "in language understandable to the subject." Asking someone to explain a word is enforcing a regulation, not being difficult.

The form must also give you "the information that a reasonable person would want to have in order to make an informed decision about whether to participate."

Federal rules list required basic elements. Check each is present and that you understood it:

• That this is research, its purpose, how long you would take part, the procedures involved, and which parts are experimental.
• Reasonably foreseeable risks and discomforts.
• Any benefits that might reasonably be expected, to you or to others.
• Alternative procedures or treatments that might help you.
• How your records will be kept confidential.
• For research with more than minimal risk, whether compensation and medical treatment are available if you are injured, and what they consist of.
• Who to contact about the research, about your rights, and about a research-related injury.
• That taking part is voluntary and you may stop at any time.
• Whether your identifiable information or biospecimens might be used in future research.

Consent forms carry additional elements too. Three answer questions people ask far too late.

Being taken off the study. Look for the section describing "anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's or the legally authorized representative's consent." This tells you what would end your participation whether you like it or not.

Costs to you. Look for "any additional costs to the subject that may result from participation in the research." If the form is vague here, get specifics in writing.

News that arrives later. Look for the promise that "significant new findings developed during the course of the research that may relate to the subject's willingness to continue participation will be provided to the subject." Trials do turn up new safety information. This clause is your claim on hearing it.

The rules also ban something. "No informed consent may include any exculpatory language through which the subject or the legally authorized representative 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 for negligence."

In plain words, a consent form may not sign away your right to hold anyone responsible for negligence. If a paragraph reads that way, ask the study team and the review board to explain it before you sign.

Every consent form must state 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."

A clinical research director quoted on NCI's site puts it in one line: "You do not have to continue just because you sign this consent today."

Your regular cancer care is not the trial's to withdraw. Confirm it out loud, and note who said it.

FDA says the discussion should be led by "a person knowledgeable about the clinical investigation and capable of answering questions." For trials with remote elements, FDA says it "does not consider obtaining informed consent to be an appropriate activity for a local HCP to perform."

Timing counts too. Consent must happen under conditions that give you "sufficient opportunity to discuss and consider whether or not to participate and that minimize the possibility of coercion or undue influence." FDA names a specific bad practice: seeking consent in preoperative areas "would generally fail to minimize the possibility of undue influence."

If you are gowned, sedated, or already on a trolley, that is the moment to say you will read it later.

Trial costs divide in two. NCI calls patient care costs those "costs that you would pay even if you weren't in a trial," which are "often covered by health insurance." Research costs are trial-specific, and NCI says "Often these costs are not covered by health insurance. But they may be covered by the trial's sponsor."

Federal law helps with the first group. Under section 2709 of the Public Health Service Act, added by the Affordable Care Act, non-grandfathered health plans may not "deny (or limit or impose additional conditions on) the coverage of routine patient costs" in an approved clinical trial.

Get three answers before signing: what goes to my insurance, what the sponsor pays, and who pays if the study drug injures me.

• Read the key information section first, then alternatives, then how you can be taken off.
• Highlight every term you cannot define and get each explained.
• Take the document home overnight. Nothing in the rules requires you to sign on the day.
• Read it once with someone who will attend appointments with you.

• What are my alternatives if I do not join, including doing nothing right now?
• What in this study is experimental, and what would I get anyway?
• What would take me off the study, and what would happen next?
• Who pays if I am injured by the study drug?
• Which parts of this will be billed to my insurance?
• How will you tell me if new safety information appears?

• Electronic Code of Federal Regulations — 45 CFR 46.116, General requirements for informed consent.
• U.S. Food and Drug Administration — Informed Consent: Guidance for IRBs, Clinical Investigators, and Sponsors.
• National Cancer Institute — Understanding Cancer Research Consent Forms.
• U.S. Food and Drug Administration — Conducting Clinical Trials With Decentralized Elements.
• National Cancer Institute — Who Pays for Clinical Trials?.
• Centers for Medicare & Medicaid Services — Affordable Care Act Implementation FAQs, Set 15.

Helpful next pages include What Is Informed Consent in a Clinical Trial?, Clinical Trial Screening Visit: What to Expect, How Are Clinical Trial Costs and Insurance Handled?, How Is Your Safety Protected in a Clinical Trial?, Quality-of-Life Questions in Cancer Clinical Trials, Comparing a Clinical Trial to Standard Treatment.