Center For Drug Evaluation And Research Application Essay

On By In 1

REGULATION OF THE MEDICAL USE OF PSYCHEDELICS AND MARIJUANA
A dissertation by Rick Doblin for his Ph.D. in Public Policy from the Kennedy School of Government, Harvard University
June 2001

 ABSTRACT

Part 1 of this dissertation analyzes the historical development and current status of the regulation of medical research with psychedelic drugs and marijuana. The analysis is based on interviews with current and former government officials, review of published and unpublished documents, and on-going discussions with all known researchers who have filed applications within the previous fifteen years seeking permission to conduct any human studies with psychedelics, or studies with marijuana in patient populations. A special analysis is made of the creation in 1989 and dissolution in 1995 of FDA's Pilot Drug Evaluation Staff, an extraordinary bureaucratic experiment that, among its many other accomplishments, established FDA's current policy of evaluating psychedelic and marijuana protocols with the same standards FDA uses for the review of all other studies.

Part 2 analyzes regulatory, ethical and methodological issues involved in the design of the Phase III studies that FDA requires to evaluate the safety and efficacy of the medical uses of psychedelics and marijuana. The standard of proof that FDA uses to evaluate data about other drugs, comparison to placebo, is determined to be optimal for the review of data about psychedelics and marijuana. A two-arm protocol design comparing psychedelic psychotherapy against psychotherapy alone is concluded to be "adequate and well-controlled." Taking into account political considerations, a four-arm study is proposed comparing three groups receiving high, medium or sub-threshold (placebo) doses of psychedelic psychotherapy with an unblinded group receiving the best alternative treatment. The economic implications of this enhanced design are determined not to impose an excessive burden on research sponsors.

Part 3 is an exercise in policy design for the regulation of the hypothetical prescription use of psychedelic psychotherapy. The legal basis for FDA's authority to impose special restrictions is reviewed, as is the regulation of thalidomide, methadone, GHB, and electroconvulsive therapy. The proposed system restricts prescribing authority to specially-licensed and trained psychiatrists working within clinical settings meeting minimum standards. Distribution is directly to psychiatrists through the mail from one centralized production and distribution facility. A national registry of patients is proposed to track all treatment sessions.

TABLE OF CONTENTS

[dissertation files in pdf format]

LIST OF CHARTS

Download pdf of charts here

  • Chronological Development of Regulations Governing the Medical Uses of Psychedelics and Marijuana
  • FDA Organizational Chart, Center for Drug Evaluation and Research, Prior to Pilot Drug, 1988
  • FDA Organizational Chart, Center for Drug Evaluation and Research, Pilot Drug Era, 1989-1995
  • FDA Organizational Chart, Center for Drug Evaluation and Research, Office of the Center Director, After Pilot Drug
  • FDA Organizational Chart, Center for Drug Evaluation and Research, Office of Review Management, After Pilot Drug
  • FDA Organizational Chart, Office of the Commissioner, 6/99 Reorganization Shift of scheduling of controlled substances to Office of the Center Director

Overview

In accordance with the PDR, the DAL, the RegImplemDAL, SC-Notice-No24, the SC-Opinions-No44, and the SC-No230, the China Food and Drug Administration (CFDA) (formerly the State Food and Drug Administration (SFDA)) is responsible for reviewing and approving clinical trial applications for all new drugs, generic drugs, and imported drugs to be registered in China. The clinical trial application review and approval process is determined by the drug classification in which an applicant chooses to register. Per the SC-Opinions-No44, the SC-No230, and described in Additional Resources (C) and (D), under a reform scheme started in 2015, a “four-color-light” strategy is being applied to the prioritization of approval decisions for drugs based upon the level of innovation and clinical need. See the SC-No230, the SC-Opinions-No19, and the SC-Opinions-No44 for details regarding innovative drugs and those deemed to have an urgent clinical need that calls for priority review.

As delineated in the SC-Opinions-No44, the SC-Notice-No51, and described in Additional Resources (B), (C), and (D), CFDA has established the following definitions and five (5) drug classifications, which determine the drug and clinical trial registration pathway:

  • New Drugs, Class 1: Innovative new drugs that have never been marketed anywhere in the world
  • New Drugs, Class 2: Improved new drugs that have never been marketed anywhere in the world
  • Generic Drugs, Class 3: Generic drugs, with equivalent quality and efficacy to the originator’s drugs, which are marketed in other countries, but not yet in China
  • Generic Drugs, Class 4: Generic drugs, with equivalent quality and efficacy to the originator’s drugs, that are already marketed in China
  • Imported Drugs, Class 5: Drugs that have been marketed in other countries, but not yet in China

The scope of the CFDA’s assessment includes Phase I through Phase IV clinical trials and bioequivalence studies. As stated in the PDR, the CFDA’s approval of a clinical trial application is dependent upon obtaining proof of the ethics committee’s (EC) approval.

The PDR states that a Chinese legal entity must submit the drug registration application. Clinical trial applications are also considered to be drug registration applications. Overseas drug manufacturers without legal representation in China must apply for product registration through an agent with professional knowledge and familiarity with Chinese laws and regulations. Also see Additional Resource (I) for more information.

Clinical Trial Review Process

As delineated in the PDR, the CDEProcs, the CTImprtChem, the CTImprtBioProduct, and the CTImprtVaccine, the CFDA’s Department of Drug Registration is responsible for conducting an administrative review of a clinical trial application, and then forwarding the submission to the Center for Drug Evaluation (CDE) for technical review.

In accordance with the SC-Opinions-No44, the SC-Notice-No51, the SC-Opinions-No19, the SC-No230, and described in Additional Resources (C) and (E), China has implemented reforms to streamline the review and approval process, including a one-time approval procedure for new drug clinical trial applications (formerly, new approvals were needed for each clinical trial phase). Under this scheme, CFDA will evaluate the scientific protocol and safety issues. Applicants should submit the research results and next-phase clinical trial protocol after completing Phase I and II studies. If there are no safety issues, the applicants can move into the next phase of the trial after communicating with CFDA’s CDE. Per Additional Resource (C), the CDE conducts on-site inspections, causal inspections, unannounced inspections, and institutional reviews of the relevant clinical trial locations, as well as production-site inspections before premarketing approval, in order to confirm the authenticity, precision, and integrity of the information submitted.

In addition, for generic drugs, the bioequivalent study will only need to be filed with the CFDA (formerly it was a review and approval procedure). For the generic drug filing, the applicant must obtain EC approval and sign a clinical study agreement with the clinical site prior to filing the bioequivalent study.

The CDE is responsible for evaluating chemistry drugs, traditional Chinese medicines, and biologic products to assess whether the safety and effectiveness data provided in the clinical trial application justifies CFDA approval. The CDE’s recommendations are reviewed by the CFDA. Additional Resources (E), (F), and (G), also provide useful information on the CFDA’s clinical trial application review and approval process.

As per the PDR, the CTImprtChem, the CTImprtBioProduct, and the CTImprtVaccine, while the CDE conducts its technical review, the National Institutes for Food and Drug Control (NIFDC) will conduct sample testing, or arrange for one of the drug testing institutes in the provinces, autonomous regions, and municipalities directly under the Central Government, to conduct sample testing concurrently to verify the quality of the drug products to be used in the study. (See the Clinical Trial Lifecycle topic, Submission Process subtopic for detailed submission requirements.)

On October 8, 2017, China’s State Council issued SC-Opinions-No42, which is a programmatic plan that deepens the reform of the review and approval system of drugs and clinical studies, as well as other measures. SC-Opinions-No42 proposed 36 reform measures, including proposals to reform clinical trial management. To implement reforms in SC-Opinions-No42 and encourage multi-center clinical research using human genetic resources, S&T-Notice-HGRNo717 and S&T-HGR-MRCTapproval establish a new approval process that took effect on December 1, 2017 and streamlines the CFDA approval process. The process establishes a leader unit and one-time declarations with CFDA. Clinical trial member units working on the same research protocol should recognize the ethical review conclusion of the head unit, and are therefore not required to repeat the ethical review. Further, S&T-Notice-HGRNo717 and S&T-HGR-MRCTapproval cancel provincial and other administrative reviews. For more information on human genetic resources, see the Specimens topic.   

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