Financial Disclosure Forms

In February the FDA issued industry guidance for the collection of financial disclosures.  I've summarized and called out a few of the sections I found most interesting.  There were certainly some items I hadn't thought about in a while so the refresher and clarifications were helpful and the appendix of Q&A was also useful.

Why are financial disclosure forms (FDF) collected?

The idea behind collecting financial disclosure information is to discover any potential bias on the part of investigators so the agency can consider this as part of the evaluation of the marketing application.  As sponsors, we try to avoid bias in trial design by using blinded randomization, placebo control, independent statisticians, specific evaluation methods, multiple study centers, etc. or other measures to minimize bias regardless of financial interest.

"Part 54 (21 CFR § 54.4(c).) does not categorically prohibit financial interests or arrangements, but it does require applicants to submit a list of clinical investigators who are full-time and part-time employees of the sponsor and to disclose or certify with respect to other investigators so that FDA can assess the possibility of bias."

Is this for every study?
Actually, the guidance covers in great detail the definition of covered clinical studies. Pretty much, all trials that support and NDA are considered covered but “This would, in general, not include phase 1 tolerance studies or pharmacokinetic studies, most clinical pharmacology studies (unless they are critical to an efficacy determination), large open safety  studies conducted at multiple sites, treatment protocols and parallel track protocols.”

What are the threshholds?

Payments for reimbursement of the conduct of the trial are not considered reportable, but grants, stock issuance, and other sorts of payments (i.e. consulting, honoraria) amounting to over $25K should be disclosed as well as any equity interest in the sponsor for up to a year after the trial exceeding $50K. 

So we’re not just talking about cash here.  The guidance spends a lot of time discussing “significant payments of other sorts (SPOOS)”, too.  This could be equipment or resources purchased for the investigator but NOT necessarily for use in the trial, entertainment costs, etc.  It could even apply to patents, proprietary interests, or future royalties (probably even more common in a device or diagnostics trial as opposed to a drug study).  For example, if you are validating a Quality of Life questionnaire or some other new assessment in your trial and a group of the investigators developed it, they might have a financial interest to disclose if they stand to make significant royalties within the year after the conclusion of the trial.

Remind the investigator to complete the form considering their financial interests and also the combined interests of their spouse and dependents - this statement is easy to overlook but can affect the dollar amount or arrangements requiring reporting.

“Materials [that are not considered SPOOS] could include the product under study as well as other products and/or equipment that are needed for the conduct of the study, such as ancillary medication and equipment used in testing required by the protocol.”

What if no Financial Disclosure was collected?

The agency requests that the “certification by the applicant that the applicant has acted with due diligence to obtain the information but was unable to do so stating a sufficient reason.”   We request an FDF prior to study initiation at an investigative site and then during monitoring we request updated financial disclosure forms if there is a status change.  At the conclusion of the trial we remind the investigator of their obligation to provide prompt updates in the year following the trial if their financial interest status changes.

What actions can the agency take?

“If FDA determines that the financial interests or arrangements of any clinical investigator raise a serious question about the integrity of the data, FDA will take any action it deems necessary to ensure the reliability of the data (21 CFR § 54.5(c)) including:

1. Initiating agency audits of the data derived from the clinical investigator in question;

2. Requesting that the applicant submit further analyses of data, e.g., to evaluate the effect of the clinical investigator's data on the overall study outcome;

3. Requesting that the applicant conduct additional independent studies to confirm the results of the questioned study; and

4. Refusing to treat the covered clinical study as providing data that can be the basis for an agency action.”

Do financial disclosure forms get submitted to the FDA?

Actually, no, the forms filed in the site master file are in the sponsor and site files but should be available for inspection upon request for up to 2 years following the approval of a new marketing application.  Also, it is entirely up to the sponsor on how to collect the financial disclosure statements as efficiently and completely as they would like.  The sponsor/applicant does provide a list of clinical investigators who do have financial interests on a Form FDA 3455 (Form FDA 2454 for investigators with no disclosable financial interest)but individual financial disclosure forms are not part of the submission and can even be maintained in an electronic certified copies rather than paper.

Can a sponsor submit the data if there was no FDF collected in every trial?

The short answer is yes, but the guideline covers in detail the obligation of an IND/IDE holder to demonstrate due diligence in having attempted to collect FDF from all applicable trials (see page 9 of the guidance, so much of the financial information is discoverable through filings of public companies and in financial records so the guidance suggests searching all available records to uncover financial interest that meets the reporting requirements).  The guidance discussed some legacy studies and other Phase I and earlier trials that don’t actually need FDF (although it is industry best practice to collect for these trials anyway).

Anything else I should know?

I found the sections on foreign studies, investigator –led/academic trials, multiple sponsors/change of sponsor, and waivers interesting and those are recommended further reading.

Thanks for following along on my summary of this new guidance.   These are non-binding recommendations so for your particular study, always consult with your legal and regulatory experts and I encourage you to read the regulations and guidance for yourself in order to apply them.  Remember that your companies working practices and SOPs will necessarily be more over-arching than the guidance and you should stick to those and discuss with your internal experts if there is any conflict. If you have additional thoughts or opinions on Financial Disclosures I would love for you to email me or leave a comment here or at The Lead CRA Facebook page.