Spotlight on clinical trial sponsorship.

Author:Mounce, Doug

The Company as Sponsor

The FDA regulations define "sponsor" as

a person who takes responsibility for and initiates a clinical investigation. The sponsor may be an individual or pharmaceutical company, governmental agency, academic institution, private organization, or other organization. The sponsor does not actually conduct the investigation unless the sponsor is a sponsor-investigator. A person other than an individual that uses one or more of its own employees to conduct an investigation that it has initiated is a sponsor, not a sponsor-investigator, and the employees are investigators. 21 CFR [section] 312.3(b) (2014) As this definition makes clear, there is a difference between sponsoring a trial and conducting a trial, and this distinction can impact the sponsor's responsibilities and liability. Further, an investigator can also operate as a sponsor, with all the attendant responsibilities, if they both initiate and conduct an investigation. (2) Id. Sponsors are primarily responsible for selecting investigators, providing them with the information necessary to conduct a trial, monitoring the investigation, ensuring that it is conducted in accordance with the general investigational plan and protocols contained in the [Investigational New Drug Application ("IND")], maintaining an effective IND with respect to the investigations, and informing investigators or the FDA of any new risks or adverse effects associated with a drug. 21 CFR [section]312.50. Investigators are also responsible for ensuring the investigation is conducted according to the investigational plan, but are also directly responsible for protecting the trial subjects, obtaining the informed consent of human subjects, and controlling the investigational drug. 21 CFR [section] 312.60.

Both the sponsor and the investigator are responsible parties. The Sponsor initiates the investigation, but the investigator actually conducts the trial.

Sponsor and Investigator Responsibilities

Subpart D of Sec. 312.50 outlines the general responsibilities of sponsors and investigators. These are shown in Table 1 below, along-with 312.20 where the responsibility for the submission of an IND to FDA is explained.

In Table 1, Section 312.52 is a unique feature because sponsors can delegate roles and responsibilities to a Contract Research Organization ("CRO"), which is able to "assume, as an independent contractor with the sponsor, one or more of the obligations of a sponsor, e.g., design of a protocol, selection or monitoring of investigations, evaluation of reports, and preparation of materials to be submitted to the Food and Drug Administration."

The Role of a Contract Research Organization (CRO)

A sponsor can delegate sponsor responsibilities to CROs. 21 C.F.R. [section] 312.52. Delegated responsibilities must be detailed by the sponsor on an attachment to the New Drug Application ("NDA") Form 1571, 21 C.F.R. [section] 312.23. An investigator, by contrast, is not allowed to delegate roles and responsibilities in terms of conducting the trial. A drug manufacturer, on the other hand, must assume responsibility for applying current good manufacturing practice (CGMP) required under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The manufacturer's responsibility is transferred if a CRO assumes the roles and responsibilities of the sponsor. (3) See 21 C.F.R. [section] 312.52 ("A sponsor may transfer responsibility for any or all of the obligations set forth in [21 C.F.R. Part 312] to a contract research organization"). A manufacturer who desires to retain commercial rights to a drug after it has been successfully tested must only show, "substantial support"--or more than 50 percent of the cost for conducting the trial. 21 C.F.R. [section] 314.50(j)(4)(iii). Delegation of sponsor roles and responsibilities has been an important feature in determining liability for subject injury.

Sponsor's Responsibility for Conducting a Clinical Trial

In the case of Kernke v. the Menninger Clinic ("Kernke"), for example, Aventis sponsored a trial to test their neuroleptic compound M100907, with Menninger Clinic defendants identified as the investigator. 173 F.Supp.2d 1117, at 1119. A patient named Joseph Kernke participated in both Phase I and Phase II of the trial, and he received the investigational drug in both phases. Id. at 1120.

Mr. Kernke was an outpatient who later voluntarily became an inpatient to take part in the study, and he signed the consent form. Id. at 1119-20. The court noted, however, that throughout the treatment he repeatedly told his relatives and the clinical staff that he desired to return home. Id. at 1120. After two months, when the Dose Limiting Toxicity had been established in Phase I, he became eligible to participate in Phase II of the trial, and again signed a consent form. Id. Three days after beginning the Phase II treatment, he left the clinic and was later found dead of exposure. Id.

The plaintiffs alleged that Aventis, as sponsor, owed Mr. Kernke the following three duties:

(1) determining patient eligibility in terms of benefit and risk, (2) securing informed consent, and (3) supervising patients. Id. at 1124.

The court disagreed, and ruled for Aventis, stating:

According to the FDA regulations, an investigator--in this case the Menninger defendants --is defined as "an individual who actually conducts a clinical investigation...." On the other hand, a sponsor--in this case Aventis--"does not actually conduct the investigation unless the sponsor is a sponsor-investigator." All of the duties alleged by plaintiffs in this case fall within the purview of the Menninger defendants as the investigator conducting the M100907 study; the duties...

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