"Actual use studies" conducted in support of Rx-to-OTC switch or direct-to-OTC new drug applications and used to show effectiveness in the OTC setting are subject to FDA's financial disclosure requirements, according to a draft guidance clarifying the agency's February 1998 final rule.

The guidance on "Financial Disclosure by Clinical Investigators" was published in the Federal Register Oct. 26.

The final rule requiring disclosure of compensation to investigators conducting clinical studies as well as the researchers' financial interests in study sponsor companies became effective Feb. 2.

One of a number of questions on the rule was "Do 'actual use studies' to support a request to switch a drug product from prescription to over-the-counter status fit the definition of a covered clinical study?"

The guidance responds, "Applicants who file supplements requesting that FDA approve a switch of a prescription drug to OTC status or who file a new drug application for direct OTC use often conduct 'actual use studies.' These may be intended to demonstrate that the product is safe and effective when used without the supervision of a licensed practitioner; in other cases, they may test labeling comprehension or other aspects of treatment."

"Actual use studies performed to support these applications would be considered covered clinical studies if they were used to demonstrate effectiveness in the OTC setting," the guidance states.

The final rule stipulates investigators must report all financial arrangements with contract research organizations acting as the sponsor of a covered study. If a CRO is "jointly supporting a covered study with the applicant company," the investigator must report payments made by the CRO and applicant company as well as financial holdings in both, as the CRO is acting as a trial sponsor, the guidance explains.

The final rule originally was issued Feb. 2, 1998 but was revised in December following concerns expressed by the Pharmaceutical Research & Manufacturers Association (¹ Also see "FDA financial disclosure threshold of $25,000 in payments to investigators set in final rule." - Pink Sheet, 9 February, 1998.).

Applicants must certify that no financial arrangements with an investigator have been made, or must disclose the size and nature of financial arrangements as well as steps taken to lessen the potential for study bias that may arise from these financial interests.

Compensation that may affect study outcome, proprietary interest in the tested product and any equity interest in the sponsor of a covered study must be disclosed.

Equity interest in a publicly held company that exceeds $50,000 in value, or payments in addition to the cost of conducting the study that have a cumulative monetary value of over $25,000 made to the investigator or the investigator's institution, also must be reported.

If the subsidiary of a larger parent company is conducting a covered clinical trial, an investigator's interest in the parent company does not need to be disclosed if the parent company is not providing "material support for the study," the draft states.

The agency will not require the construction of "elaborate internal computerized tracking systems" to collect required information as long as detailed records are maintained; questionnaires to collect the information from investigators will be acceptable.

Companies have the flexibility to collect the information "in as efficient and least burdensome [a] manner as possible," the guidance states.

Although the possibility for a waiver from collecting the investigators' financial information exists, FDA maintained it is unlikely "that any waivers will be justified for studies begun after February 2, 1999."

Financial information should be collected prior to the start of the study, but investigators also are required to provide information on financial interests during the course of the study and for one year after its completion.

Sponsors must obtain a commitment from the investigators to continue reporting financial information, including reporting for one year following completion of the study.

In place of a certification or disclosure statement, applicants unable to obtain the information despite "due diligence" may submit a statement depicting their efforts.

OTC "Actual Use Studies" Subject To Financial Disclosure Requirements

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