Informed consent for client-owned animal studies

An owner consent form must document that the animal's owner, after being told everything about the study that could matter to the decision, voluntarily agrees to let the animal take part. That is how FDA's Center for Veterinary Medicine defines informed consent in its draft Guidance #282, which recommends a consent form for every study that enrolls client-owned dogs, cats or horses. No federal regulation for animal studies lists the contents of the form; the content comes from the study's protocol and from Good Clinical Practice. A signature on a phone counts. The federal ESIGN Act gives an electronic signature the same legal effect as ink, and when the study's records fall under an FDA records rule, 21 CFR Part 11 adds conditions the signing system and the organization must meet.

Which rule asks for consent

Three texts matter in the United States, and they ask different things.

21 CFR 511.1 is the rule for shipping an unapproved new animal drug for a clinical investigation. It exempts the shipment from the approval requirement if its conditions are met. Under 511.1(b)(7), investigators must be qualified by scientific training and experience, keep complete records of the investigation, and retain copies for two years after the study ends or the drug is approved. Under 511.1(b)(8), the sponsor must monitor the study, promptly report to FDA and to all investigators any finding that suggests a significant hazard, and must not represent the drug as safe or effective for the use under investigation. The words "consent" and "owner" do not appear in 511.1. The consent duty comes from elsewhere.

21 CFR 514.117(b)(2) is the hook for studies meant to support an approval. It requires the study to be conducted under "an appropriate standard of conduct that addresses, among other issues, study conduct, study personnel, study facilities, and study documentation," and the protocol must state the intention to follow "a standard of conduct acceptable to FDA." That standard is VICH GL9, Good Clinical Practice, which FDA publishes as Guidance #85. The European Medicines Agency describes GL9 as guidance on "the design and conduct of all clinical studies of veterinary products in the target species," in force since July 2001, written so that the regulators in the VICH regions accept each other's data.

Draft Guidance #282, issued by CVM in September 2023 and still a draft, is the only FDA document about the consent form itself. It defines informed consent as "a documented process by which an owner or owner's agent voluntarily confirms the owner's willingness to allow their animal(s) to participate in a particular study, after having been informed of all aspects of the study that may be relevant to the owner's decision to participate." It says sponsors and investigators should give owners "adequate information and time to allow for an informed decision," and it recommends that "all studies conducted with client-owned companion animals use an ICF and be conducted in accordance with Good Clinical Practice guidelines." A draft guidance is CVM's current thinking, not a requirement. Its full text is a PDF on FDA's site and is worth reading before the form is written.

How the study design changes the answer

An observational study carries the lightest load, but the owner is still giving the study a record about their animal, and most state practice acts release a veterinary record to a third party only with the client's authorization. The consent form is where that authorization is written down. For a study of an unapproved product, the form also has to respect 511.1(b)(8)(iv): nothing in it may say or imply that the product is safe or effective.

What the form must contain

The definition in draft #282 sets the test: the owner must be informed of every aspect of the study that could matter to the decision. A form that passes it covers at least these points, in the order an owner would ask them.

1. What the study is for, in one or two sentences, and who is running it.
2. What will be done to the animal, how often, and for how long, including visits, samples and anything the owner does at home.
3. What the product is and its status. For an unapproved product, that it is investigational and that its safety and effectiveness have not been established. Never the reverse.
4. The risks that are known, and that there may be risks that are not.
5. What the study pays for, what the owner pays for, and what happens if the animal needs care because of the study.
6. That taking part is voluntary, that the owner can withdraw at any time, and what happens to the animal and the data if they do.
7. Who will see the records: the study team, the sponsor's monitor, and the regulator if the data are submitted. How the owner's identity is kept apart from the study data.
8. Whom to contact with a question or a problem, and how.
9. A signature block that shows the signer's printed name, the date and time, and what the signature means. If someone other than the owner signs, their authority to decide for the animal.

Write it for a reader in a hurry. Colorado State University's clinical review board notes that the National Institutes of Health puts the ideal reading level of a consent form at sixth grade, and that it does not require investigators to reach that ideal. It is a fair target.

Can it be signed on a phone?

Yes, under two layers of law.

The first is the ESIGN Act, 15 U.S.C. 7001. Section 7001(a) says a signature or record "may not be denied legal effect, validity, or enforceability solely because it is in electronic form." Section 7001(c) adds that where a law requires a consumer disclosure in writing, the consumer must first agree to receive it electronically after being told about the paper option and how to withdraw that agreement. Section 7001(d) says a record-keeping duty is met by an electronic record that "accurately reflects the information" and "remains accessible" for the required period. A consent form signed on a phone, kept unchanged and retrievable, meets this layer.

The second layer applies only when the records are kept under an FDA records requirement, which 11.1(b) makes the scope of 21 CFR Part 11. For a study under an INAD exemption, the investigator's records under 511.1(b)(7) are such records, and the consent is one of them. Part 11 then asks for the following.

• An electronic signature is "a computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual's handwritten signature" (11.3(b)(7)).
• The signed record shows the signer's printed name, the date and time, and the meaning of the signature (11.50(a)).
• The signature is linked to its record so it "cannot be excised, copied, or otherwise transferred to falsify an electronic record by ordinary means" (11.70).
• Each signature is unique to one person and never reused (11.100(a)).
• A signature that is not biometric uses "at least two distinct identification components such as an identification code and password" (11.200(a)(1)).
• Before using electronic signatures, the organization certifies to FDA that its electronic signatures are the legally binding equivalent of handwritten ones (11.100(c)). That letter is the sponsor's or institution's to send, not the software vendor's.

In Signalment, the owner opens the study on their own phone, reads the exact version of the consent text, confirms they have read it and are authorized to decide for the animal, types their full name and re-enters their password. The signature is bound to the hash of that text version with the time. The owner keeps a copy, can withdraw at any time, and no study entry for the animal is accepted until the current consent version is signed. A paper form can be recorded instead, with a scan. Signalment does not yet have structured fields for an owner's agent or a witness; those details go in the consent text and the paper record. How an owner sees the study is shown at signalment.app/owners.

What stays the sponsor's and the investigator's job

Signalment is a data system. It holds the consent version, the signature and the audit trail. It does not write the protocol, decide what the form says, obtain ethics review, file the INAD, send the Part 11 certification letter, or report a hazard to FDA. Those belong to the sponsor and the investigator, and the monitor checks that consent was obtained and recorded before each animal took part.

The steps, in order:

1. Write the protocol, then write the consent form from it. Every procedure in the protocol appears in the form.
2. Take both to the ethics review your institution or funder requires. A privately owned practice may have none; a university will.
3. Give the owner the form and time to read it before enrollment. Draft #282 asks for adequate information and time.
4. Obtain the signature before any study procedure, and keep the signed copy with the raw data.
5. When the protocol changes in a way that affects the owner, issue a new consent version and obtain it again.
6. Record every withdrawal, with the date, and stop the animal's study entries from that point.

For the study around the form, see How to run a clinical study for a pet supplement.

Sources

• 21 CFR 511.1, new animal drugs for investigational use: https://www.ecfr.gov/current/title-21/section-511.1
• 21 CFR 514.117, adequate and well-controlled studies: https://www.ecfr.gov/current/title-21/section-514.117
• 21 CFR Part 11, electronic records and electronic signatures: https://www.ecfr.gov/current/title-21/part-11
• FDA CVM draft Guidance #282, Informed Consent Forms for Studies that Enroll Client-Owned Companion Animals (September 2023): https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-282-informed-consent-forms-studies-enroll-client-owned-companion-animals
• FDA CVM update, FDA seeks public comment on guidance related to informed consent in companion animal studies (September 14, 2023): https://www.fda.gov/animal-veterinary/cvm-updates/fda-seeks-public-comment-guidance-related-informed-consent-companion-animal-studies
• European Medicines Agency, VICH GL9 Good clinical practices: https://www.ema.europa.eu/en/vich-gl9-good-clinical-practices-scientific-guideline
• VICH, GL9 Good Clinical Practice: https://vichsec.org/guidelines/pharmaceuticals-pharma-efficacy-good-clinical-practice/
• 15 U.S.C. 7001, ESIGN Act, general rule of validity (Cornell Legal Information Institute): https://www.law.cornell.edu/uscode/text/15/7001
• Colorado State University Clinical Review Board, best practices: https://www.research.colostate.edu/orcc/clinical-review-board/best-practices/