Expanding Access to Investigational Therapies for HIV Infection and AIDS (1991) / Chapter Skim
Currently Skimming:
1 HISTORICAL PERSPECTIVE
1 HISTORICAL PERSPECTIVE
Pages 5-18
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 5... ...
The ddI controversy exposed sharp differences of opinion within the medical community about the appropriateness of making investigational drugs-drugs not yet approved for marketing by the FDA available for therapeutic purposes. In August 1989, the Public Health Service (PHS)
|
From page 6... ...
~ ~ _ ~ A brief review of earlier approaches to expanded access and a summary of the drug approval process prior to the start of the AIDS epidemic help place the debate over the parallel track mechanism in perspective. EARLY DEVELOPMENT OF EXPANDED ACCESS Modern drug regulation in the United States began in 1938 with enactment of the Federal Food, Drug, and Cosmetic Act, prompted by the elixir sulfanilamide tragedy of November 1937 (more than 100 people died when a drug containing the poisonous solvent diethylene glycol was marketed without animal tests)
|
From page 7... ...
Questions of expanded access did not arise because there were no substantive barriers to obtaining investigational drugs for therapeutic purposes. Drug Amendments of 1962 Public attention did not focus again on the drug regulatory apparatus until July 1962, when a story in the Washington Post disclosed links between the experimental drug thalidomide and severe birth defects.
|
From page 8... ...
In the 1960s, FDA medical officers permitted access to investigational drugs under several mechanisms: orphan drug INDs, individual investigator INDs, and compassionate use INDs. The orphan drug concept actually predated the 1962 amendments and remains in use today.
|
From page 9... ...
The individual investigator IND enabled physicians to obtain experimental drugs for therapeutic purposes when it was not possible to enroll their patients in existing clinical trials. By the end of the 1960s, this concept had been incorporated into the compassionate use IND, which also covered the provision of experimental drugs to patients during FDA review of a new drug application, or NDA (the document submitted by a sponsor after the completion of clinical trials to request permission for marketing)
|
From page 10... ...
The larger trials allow researchers to acquire more information about efficacy and to identify some of the less common side effects associated with an experimental drug. If the net results of all three phases of clinical trials are favorable and the sponsor decides to market the drug, it submits a new drug application to the FDN The NDA must contain all the scientific information gathered in the previous years and typically runs 100,000 pages or more.
|
From page 11... ...
There was a perception that government scientists were more interested in maintaining the scientific standards of clinical trials than in providing new options for the thousands of patients who were dying as a result of HIV infection. Government scientists, on the other hand, were frustrated by misconceptions surrounding the drug development process.
|
From page 12... ...
As noted in Chapter 7, however, much more work remains to be done to solve the access problem. Accelerating the Pace of Drug Development One of the hardest messages to convey to desperately ill patients has been that no changes in regulations or clinical trials can increase access to drugs unless potential drug candidates are already in the pipeline.
|
From page 13... ...
In addition, FDA established the AIDS Coordination Staff to integrate the agency's various AIDS-related activities and to interact with other agencies and outside groups interested in AIDS drug development. Expedited Development Perhaps the most fundamental change, however, involved the clinical trials process itself.
|
From page 14... ...
These mechanisms, which incorporate the expanded use practices that began in the 1960s, evolved from a growing awareness on the part of drug sponsors, government scientists, and others that the informal procedures of the past would not be sufficient to handle the distribution of investigational drugs to AIDS patients. The complexity of HIV infection and the potential toxicity of some drug candidates discouraged FDA medical officers from approving expanded access protocols for AIDS drugs on the basis of a few quick telephone conversations.
|
From page 15... ...
Some critics believe that when the final IND regulations emerged in 1987, the definition of treatment IND was much narrower. The treatment IND mechanism allows patients suffering from serious or life-threatening conditions for which there is no satisfactory alternative therapy to obtain a promising experimental drug.
|
From page 16... ...
Parallel track protocols could be approved for promising investigational drugs when the evidence for effectiveness was less than that required for a treatment IND. Several months later, an FDA Advisory Committee meeting convened by the FDA and a subgroup convened by the National AIDS Program Office began efforts to define the structure of the parallel track system.
|
From page 17... ...
For example, the authors of the proposed policy statement on the parallel track indicate that expanded phase 1 trials should provide some information about potential interactions between an investigational drug and other drugs commonly used in the patient population. Other physicians suggest that expanded phase 1 trials should compare different doses of an experimental drug, primarily to avoid problems similar to those that arose with zidovudine.
|
From page 18... ...
In addition, the time required to provide sufficient information to hundreds of IRBs around the country would defeat the main purpose of the parallel track-rapid dissemination of investigational drugs to desperately ill patients. To overcome this problem, the working group has proposed a national human subjects protection review panel to provide continuing ethical oversight of all parallel track protocols.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.