Running a sponsor trial in a specialty practice

A sponsor expects a practice site's records to show, for every animal, who observed what and when, with the first value kept and a reason given whenever something was changed; a consent signed by the owner before the animal took part; the protocol version in force; the study product received, given and left over; every adverse event passed to the sponsor promptly; and a monitor able to check all of it against the clinic's own chart. The standard is FDA Guidance #85, which is VICH GL9, and when the product is an unapproved new animal drug the records rule is 21 CFR 511.1. A coordinator keeps up by recording at the visit rather than after it, by keeping one record instead of a chart, a binder and a spreadsheet, and by giving the monitor something to read instead of something to ask for.

Where the expectations come from

No regulation names good clinical practice. 21 CFR 514.117(b)(2) says an adequate and well-controlled study is conducted under "an appropriate standard of conduct that addresses, among other issues, study conduct, study personnel, study facilities, and study documentation," and that the protocol states the intention to follow a standard acceptable to FDA. Guidance #85 is that standard. Section 514.117(c)(2) adds that a field study uses a control, minimizes bias, and records observations in enough detail to permit evaluation, and 514.117(e) says reports lacking those details will not be considered.

GL9 says in its introduction that it should be followed when developing data intended for regulatory authorities, and in section 2.6 that studies not intended for regulatory support are outside its scope. Draft Guidance #282 goes further for dogs, cats and horses: CVM recommends that all studies with client-owned companion animals use an informed consent form and follow GCP. It is a draft, so current thinking rather than a requirement.

For an unapproved new animal drug, 21 CFR 511.1(b)(7) requires an investigator qualified by scientific training and experience, who keeps complete records of the investigation including receipt and disposition of each shipment, retains them for two years after the investigation ends or the drug is approved, and sends adequate and timely reports to the sponsor. Section 511.1(b)(8) requires the sponsor to retain those reports, to provide current monitoring by a qualified person, to investigate and report to FDA and to all investigators any finding that may suggest a significant hazard, and never to represent the drug as safe or effective for the use under investigation.

When those records are kept electronically, 21 CFR Part 11 applies, because 11.1(b) covers electronic records kept under any records requirement in agency regulations. Section 11.10 asks for validation, accurate and complete copies in human-readable and electronic form, access limited to authorized people, secure computer-generated time-stamped audit trails whose changes do not obscure earlier entries, authority checks on who may sign, and trained users. FDA's October 2024 questions-and-answers guidance on electronic systems, which lists the Center for Veterinary Medicine among its issuing centers and names new animal drugs in its scope, says the audit trail must capture every change, the person, the date and time, and the old and new values, and should include the reason. Guidance #287 says CVM verifies study conduct by evaluating the raw data, and that the audit trail is submitted when raw data were collected by an electronic data capture system.

What the records must show

GL9 section 8.3.1 asks that raw data, handwritten or electronic, be attributable, original, accurate, contemporaneous and legible, and that in an automated system the person making direct input records their name and the date at the time of input. Section 8.3.5 says a handwritten correction is one line through the original, initialed, dated and given a reason. Section 8.3.6 says that when data are entered directly into a computer, the electronic record is the raw data, each entry and change is made under the electronic signature of the person making it, and changes are kept in an audit trail. A coordinator who copies a chart into a sponsor form a week later has produced neither original nor contemporaneous data; section 1.24 says transcribed data are not raw data.

The table lists what a monitor asks to see at a site visit, and where the expectation sits.

The monitor's own duties are in GL9 section 5.2: to ensure consent was obtained and recorded, that all data are correctly and completely recorded, that illegible, missing or corrected documentation is fully explained, that product storage and dispensing are documented, and to review the raw data against the protocol. Section 3.1.5 says one person may not be both investigator and monitor, so the practice's study lead cannot check their own site.

How the design changes the answer

• An observational study, nothing assigned. No INAD, so 511.1 does not apply, and GL9 is outside its own scope unless the data are meant for a regulator. Part 11 applies only if the records are kept under an FDA records requirement, which is rare here. Draft Guidance #282 still recommends a consent form, and the practice's record confidentiality rules still govern what leaves the chart.
• A marketed product used as labelled. No INAD. Adverse events reach FDA through the product's applicant under 21 CFR 514.80: the applicant files each serious, unexpected event within 15 working days of first learning of it, and a non-applicant forwards what it hears to the applicant within three working days. If the sponsor means the study for FDA, GL9 and Part 11 apply as above.
• An unapproved product, including a research peptide or a compounded preparation. The sponsor files the Notice of Claimed Investigational Exemption under 511.1(b)(4) before any shipment; the label carries the caution in 511.1(b)(1); the receipt and disposition records and the two-year retention in 511.1(b)(7) are the site's; and the 2024 guidance cites 511.1(b)(7)(ii) and (b)(8)(i) among the records rules that bring Part 11 in. No recruitment page or consent form may suggest the product is safe or effective, under 511.1(b)(8)(iv).

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

Signalment is a data system. The protocol and its amendments are prepared and signed by the sponsor and the investigator (GL9 4.2.6, 4.2.7). The sponsor files any INAD notice (511.1(b)(4)), appoints the monitor (GL9 4.2.4), reports adverse events to the regulator (GL9 4.2.10; 511.1(b)(8)(ii)), and keeps responsibility for data quality however much it delegates (GL9 4.3.1). The investigator obtains consent and decides what the form says (GL9 3.2.13; GFI #282), complies with the humane-care rules that apply to the site (GL9 3.2.12), and trains the staff who enter data (GL9 3.2.7; 21 CFR 11.10(i)). Any ethics review the institution or a funder requires is theirs to arrange. Before an organization uses electronic signatures on FDA-regulated records, it certifies to FDA in a letter that those signatures are the legally binding equivalent of handwritten ones (11.100(c)). The 2024 guidance also expects the sponsor to evaluate its software provider's validation, access controls, copies, audit trails and backup, and to put the arrangement in a written agreement; ask the sponsor early what it wants from the practice and what from the vendor.

How a coordinator keeps up

1. Record at the visit, in the system of record, under your own login. Name and date at input is what section 8.3.1 asks, and a shared login breaks attribution.
2. Never retype. If the clinic chart is the source, bring it into the study record as a scan and transcribe from it with the source quoted, so the monitor can verify each line.
3. Change nothing in place. Every correction carries the old value, the new value, your name, the time and a reason.
4. Take consent before anything else, on the version of the text the sponsor approved, and keep the owner's copy.
5. Keep the product log current on the day: what arrived, what was dispensed to whom, what came back.
6. Tell the sponsor of every adverse event and every deviation as soon as you know of it; the date you reported is itself a record.
7. Log every call and visit from the sponsor or the monitor with the date, the people and the subject.
8. Before the monitor arrives, read the audit trail for the period yourself.

Signalment is built for the first four. The site's forms, the owner's eDiary and eConsent, and scanned clinic records read into proposed form lines with a source quote each, accepted by a person, sit in one record whose audit trail is append-only, hash-chained and exported with its fingerprints so the monitor can verify it offline, as An audit trail a monitor can verify offline explains. Signatures re-check the signer's password and bind to the hash of what was signed, and monitor queries live on the record they concern. What it does not do yet: a drug shipment and reconciliation ledger, VeDDRA coding of adverse events, and SAS or SEND exports, so the product log in point five stays in the sponsor's system or on paper until then. The practice page at signalment.app/practices shows the site's side of a study.

Sources

• 21 CFR 514.117, adequate and well-controlled studies: https://www.ecfr.gov/current/title-21/section-514.117
• 21 CFR 511.1, new animal drugs for investigational use: https://www.ecfr.gov/current/title-21/section-511.1
• 21 CFR Part 11, electronic records and signatures: https://www.ecfr.gov/current/title-21/part-11
• 21 CFR 514.3, definitions: https://www.ecfr.gov/current/title-21/section-514.3
• 21 CFR 514.80, records and reports for approved new animal drugs: https://www.ecfr.gov/current/title-21/section-514.80
• FDA Guidance #85, VICH GL9, Good Clinical Practice: https://www.fda.gov/media/70333/download
• FDA draft Guidance #282, Informed Consent Forms for Studies that Enroll Client-Owned Companion Animals: https://www.fda.gov/media/172056/download
• FDA Guidance #287, Raw Data for Safety and Effectiveness Studies: https://www.fda.gov/media/177901/download
• FDA, Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers (October 2024): https://www.fda.gov/media/166215/download