Research · 9 min read
What Informed Consent Has to Contain in a Clinical Trial
The regulation lists eight things a research subject must be told and six more where they apply. It also bans one kind of sentence outright, and that ban is the most useful thing on the page for anyone reading any health agreement.
Key takeaways
- The part governs clinical investigations regulated by FDA, not routine care and not a company's own agreements.
- Consent must be sought with sufficient opportunity to consider and with coercion and undue influence minimized.
- The information must be in language understandable to the person receiving it.
- No consent may include exculpatory language making someone waive or appear to waive legal rights, or releasing or appearing to release anyone from liability for negligence.
- Eight basic elements must be provided, including alternatives, confidentiality and FDA record inspection, injury contacts, and the voluntariness statement.
- Six additional elements apply where appropriate, including unforeseeable risks, investigator-initiated termination, extra costs, and the approximate number of subjects.
- Applicable clinical trials require a specific printed statement about the federal clinical trials registry.
- Documentation is a board-approved written form signed and dated at the time of consent, with a copy given to the signer, or a short form with a witness and a board-approved summary.
- The exception from consent requires two people to certify four findings in writing, with the documentation filed with the review board within five working days.
- The requirements do not preempt other laws requiring more disclosure, and do not limit a physician's authority to provide emergency care.
Answer first: this rule is about research, not routine care
The scope sentence says where the part applies, and it is narrower than the phrase informed consent suggests in everyday use.
It applies to all clinical investigations regulated by the agency under two named statutory sections, and to clinical investigations supporting applications for research or marketing permits for regulated products.
The product list is long. It includes drugs for human use, medical devices, biological products, infant formulas, food and color additives, and electronic products. It also includes foods and dietary supplements that bear a nutrient content claim or a health claim.
So this is the standard that applied to the trials a company cites, not the standard governing the checkbox on its intake form.
The general requirement is stated as a prohibition. There are three named exceptions. Otherwise, no investigator may involve a human being as a subject in covered research without the legally effective informed consent of the subject or the subject's legally authorized representative.
How consent must be sought, and one sentence that is banned
Three conditions surround the act of asking, and the last one is a flat prohibition worth carrying into any document.
An investigator shall seek consent only under circumstances that provide sufficient opportunity to consider whether or not to participate, and that minimize the possibility of coercion or undue influence.
The information given shall be in language understandable to the subject or the representative.
Then the ban. No informed consent, whether oral or written, may include any exculpatory language. That covers language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights. It also covers language that releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.
Read the two verbs. Waive or appear to waive. Releases or appears to release. The prohibition reaches wording that merely looks like a waiver, not only wording that legally works as one.
The eight things every subject has to be told
The basic elements are listed, and each one answers a question a reasonable person would ask.
That the study involves research, an explanation of its purposes and the expected duration of participation, a description of the procedures to be followed, and identification of any procedures which are experimental.
A description of any reasonably foreseeable risks or discomforts. A description of any benefits to the subject or to others which may reasonably be expected.
A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject.
A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained, and noting the possibility that the agency may inspect the records.
For research involving more than minimal risk, an explanation of whether any compensation and whether any medical treatments are available if injury occurs, what they consist of, or where further information may be obtained.
An explanation of whom to contact for answers about the research and about subjects' rights, and whom to contact in the event of a research-related injury.
And a statement that participation is voluntary. It says refusal will involve no penalty or loss of benefits the subject is otherwise entitled to, and that the subject may discontinue at any time without penalty or loss of benefits.
Six more, where they apply
The additional elements are provided when appropriate, and several of them explain things people find out late.
A statement that the 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.
Anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent.
Any additional costs to the subject that may result from participation.
The consequences of a decision to withdraw, and procedures for orderly termination of participation.
A statement that significant new findings developed during the research which may relate to the subject's willingness to continue will be provided to the subject.
And the approximate number of subjects involved in the study.
That last one is worth noticing when reading a trial's own consent materials. The number of people was something participants were meant to be told.
The registry sentence, printed word for word
One paragraph prescribes an exact sentence rather than a topic, which makes it unusually easy to check.
For applicable clinical trials, the following statement shall be provided to each subject in informed consent documents and processes.
A description of this clinical trial will be available on the federal clinical trials website, as required by United States law. That website will not include information that can identify the subject. At most, it will include a summary of the results. And the subject can search it at any time.
The regulation explains the purpose in the same paragraph. It notifies the subject that clinical trial information has been or will be submitted for inclusion in the clinical trial registry databank.
That paragraph is the link between an individual's consent form and the public record of the trial they joined.
How consent gets documented, and the short-form route
Documentation has its own section with two permitted forms.
The default is a written consent form approved by the review board and signed and dated by the subject or their legally authorized representative at the time of consent. A copy shall be given to the person signing.
The first permitted form is a written consent document embodying the required elements. It may be read aloud, but the investigator must give the subject or representative adequate opportunity to read it before signing.
The second is a short form stating that the required elements have been presented orally.
That route carries four extra requirements. There must be a witness to the oral presentation. The review board must approve a written summary of what is to be said. Only the short form is signed by the subject.
And the signatures fan out. The witness signs both the short form and a copy of the summary, and the person actually obtaining consent signs a copy of the summary. The subject gets a copy of the summary in addition to a copy of the short form.
The exception, and how narrow it is
There is an exception from the general requirement, and it is built to be hard to reach.
Consent is deemed feasible unless both the investigator and a physician who is not otherwise participating in the investigation certify in writing to four things.
That the subject is confronted by a life-threatening situation necessitating use of the test article. That consent cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the subject.
That time is not sufficient to obtain consent from the subject's legal representative. And that there is available no alternative method of approved or generally recognized therapy providing an equal or greater likelihood of saving the subject's life.
Say immediate use is required to preserve life and there is no time for the independent determination. The investigator's determinations are made, then reviewed and evaluated in writing by a non-participating physician within five working days of the use.
Either way the paperwork goes to the review board within five working days after the test article is used.
Two independent people, four certified findings, and a written record filed within a week. That is the shape of the exception, and it is not a general permission to skip consent.
What the regulation says it does not do
Two closing paragraphs limit the reach of the whole scheme, in opposite directions.
The requirements are not intended to preempt any applicable federal, state or local laws which require additional information to be disclosed for informed consent to be legally effective.
So this list is a floor. Another law can require more, and satisfying this list does not answer a state-law question.
And nothing in the regulations is intended to limit the authority of a physician to provide emergency medical care to the extent permitted under applicable federal, state or local law.
Those two sentences together explain why a consent form can be longer than the list above, and why the list is not the whole of what a clinician may do.
What to take from this when reading anything else
Three of these rules travel well beyond a research setting.
The exculpatory language ban is the strongest of them. In this context, a document may not contain wording that makes a person waive or appear to waive legal rights, or that releases or appears to release anyone from liability for negligence. That is a specific thing to look for in any agreement you are handed.
The understandable-language requirement is the second. Information given shall be in language understandable to the person receiving it, which is a standard about the reader rather than the drafter.
And the voluntary-participation element is the third. A statement that refusal involves no penalty or loss of benefits, and that a person may discontinue at any time without penalty or loss of benefits, is a defined element of a valid consent here.
None of those three transfers automatically to a commercial contract. They are worth knowing because they show what a document written to be understood and refused actually looks like.
What this page does not tell you
Three boundaries, stated where you can see them.
Everything above is drawn from the federal regulation on protection of human subjects in clinical investigations. It does not describe the rules for routine medical care, and it does not govern a company's terms of service or intake form.
One section of this part concerns a presidential waiver of consent for members of the armed forces in a military operation. It has nothing to do with this subject and is deliberately not described.
And no company's consent materials or cited trial was examined. No seller is named.
Sources
- 21 CFR Part 50 — Protection of Human SubjectsSection 50.1(a) for the scope covering all clinical investigations regulated by FDA under sections 505(i) and 520(g) of the Federal Food, Drug, and Cosmetic Act and clinical investigations supporting applications for research or marketing permits, and for the enumerated product categories including foods and dietary supplements bearing a nutrient content claim or a health claim, infant formulas, food and color additives, drugs for human use, medical devices for human use, biological products for human use, and electronic products. Section 50.20 for the general requirement that, except as provided in §§ 50.22, 50.23 and 50.24, no investigator may involve a human being as a subject in covered research without the legally effective informed consent of the subject or the subject's legally authorized representative; for seeking consent only under circumstances providing sufficient opportunity to consider participation and minimizing the possibility of coercion or undue influence; for the information being in language understandable to the subject or representative; and for the prohibition on any exculpatory language through which the subject or representative is made to waive or appear to waive any legal rights, or which releases or appears to release the investigator, sponsor, institution or its agents from liability for negligence. Section 50.23(a)(1) through (4) for the four written certifications by the investigator and a non-participating physician; 50.23(b) for the immediate-use route with review and written evaluation by a non-participating physician within 5 working days; 50.23(c) for submitting the documentation to the IRB within 5 working days after use. Section 50.25(a)(1) through (8) for the eight basic elements of informed consent; 50.25(b)(1) through (6) for the six additional elements provided when appropriate; 50.25(c) for the required statement to subjects of applicable clinical trials about the federal clinical trials website, its exclusion of identifying information, its inclusion at most of a summary of results, the subject's ability to search it at any time, and the paragraph's stated purpose of notifying the subject that trial information has been or will be submitted to the clinical trial registry databank; 50.25(d) for the requirements not preempting applicable Federal, State or local laws requiring additional information for informed consent to be legally effective; 50.25(e) for nothing limiting a physician's authority to provide emergency medical care to the extent permitted under applicable law. Section 50.27(a) for documentation by a written consent form approved by the IRB and signed and dated by the subject or representative at the time of consent, with a copy given to the person signing; 50.27(b)(1) for the full written consent document and the adequate opportunity to read it before signing; 50.27(b)(2) for the short form route, the witness to the oral presentation, the IRB-approved written summary, the signature pattern across the short form and the summary, and the copies given to the subject. Section 50.23(d), covering a presidential waiver of consent for members of the armed forces, is deliberately not described in the article.
Frequently asked questions
Does this rule cover a telehealth intake form?
No. The part applies to clinical investigations regulated by FDA under two named statutory sections. It also applies to clinical investigations supporting applications for research or marketing permits for regulated products. Those include drugs, devices, biological products, infant formulas, food and color additives, electronic products, and foods and dietary supplements bearing a nutrient content or health claim. It is the standard for research, not for routine care or for a company's own agreements.
What has to be in a consent form?
Eight basic elements. That the study is research, with its purposes, expected duration, procedures and any experimental procedures identified. Reasonably foreseeable risks or discomforts. Reasonably expected benefits. Appropriate alternative procedures or courses of treatment that might be advantageous. The extent to which confidentiality will be maintained, and that FDA may inspect records. For more than minimal risk, whether compensation and medical treatments are available if injury occurs. Whom to contact about the research, subjects' rights and a research-related injury. And a statement that participation is voluntary and may be discontinued at any time without penalty or loss of benefits.
What are the additional elements?
Six, provided when appropriate. Currently unforeseeable risks, including to an embryo or fetus. Anticipated circumstances in which the investigator may terminate participation without regard to the subject's consent. Any additional costs resulting from participation. The consequences of withdrawing, and procedures for orderly termination. A statement that significant new findings relating to willingness to continue will be provided. And the approximate number of subjects involved in the study.
Can a consent form ask me to waive my rights?
No. The regulation bars exculpatory language in any informed consent, whether oral or written. That covers language through which the subject or representative is made to waive or appear to waive any of the subject's legal rights. It also covers language that releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence. The phrasing reaches language that appears to do so, not only language that succeeds.
Does the form have to be signed?
Generally yes. Informed consent shall be documented by a written consent form approved by the review board. It is signed and dated by the subject or their legally authorized representative at the time of consent, and a copy shall be given to the person signing. The form may either embody the required elements in full, or be a short form stating the elements were presented orally. That second route requires a witness, a board-approved written summary, and a specific pattern of signatures on the short form and the summary.
Is there a sentence about ClinicalTrials.gov?
Yes, and it is printed in the regulation. For applicable clinical trials, subjects must be given a statement about the federal clinical trials website. It says a description of the trial will be available there as required by United States law, and that the site will not include identifying information. It adds that at most the site will include a summary of the results, and that the subject can search it at any time. The paragraph explains its purpose is to notify the subject that trial information has been or will be submitted to the registry databank.
When can consent be skipped?
Only under a narrow exception. Both the investigator and a physician who is not otherwise participating must certify four things in writing. That the subject faces a life-threatening situation necessitating use of the test article. That consent cannot be obtained because of an inability to communicate with, or obtain legally effective consent from, the subject. That time is insufficient to obtain consent from a legal representative. And that no alternative approved or generally recognized therapy offers an equal or greater likelihood of saving the subject's life. Where immediate use is required, a non-participating physician reviews and evaluates in writing within five working days, and the documentation goes to the review board within five working days of use.
Does meeting this list satisfy state law?
Not necessarily. The regulation says its requirements are not intended to preempt any applicable federal, state or local laws requiring additional information to be disclosed for informed consent to be legally effective. It also says nothing in the regulations is intended to limit a physician's authority to provide emergency medical care to the extent permitted under applicable law.