Restricting access to unapproved drugs: a compelling government interest?

AuthorCurrie, Peter M.
  1. INTRODUCTION II. FDA DRUG APPROVAL PROCESS A. History B. The Clinical Trial System C. Expanded Access Programs 1. Treatment IND 2. Group C Treatment IND 3. Emergency Use IND 4. Parallel Track III. BALANCING INDIVIDUAL RIGHTS WITH STATE PROMOTION OF PUBLIC HEALTH A. The Limits of Paternalistic Regulation B. Safeguarding the Clinical Trial System 1. Scope of the Constitutional Right of Access 2. Research Subject Motivation 3. Will a Market Exist? IV. CONCLUSION I. INTRODUCTION

    The prospective review and approval of drugs is central to the public health mission of the United States Food and Drug Administration (FDA). Requiring pharmaceutical manufacturers to generate information about their products' safety and efficacy enables the agency to evaluate the risks and benefits associated with their use, thereby preventing overly harmful products from reaching the market. The majority of consumers benefit from this intervention by gaining access to an array of drugs that are proven to be safe and effective. Thus, governmental regulation in this area is arguably justified because the aggregate social welfare is substantially improved.

    However, this majoritarian view overlooks the concentrated costs that the drug approval process imposes upon minority groups within society. Drug testing is both resource intensive and time consuming, with an average of eight years required for human clinical testing alone. (1) For individuals suffering from terminal illness who have exhausted conventional therapies, this delay in access can be fatal. Many terminally ill patients are therefore willing to tolerate vastly greater therapeutic risks in an effort to find a cure. Under the current regulatory structure, however, willingness to tolerate, risk does not necessarily translate into access to unapproved drugs.

    The tension between drug safety and access to developing experimental drugs most recently came to the forefront in 2003, when the Abigail Alliance for Better Access to Developmental Drugs [hereinafter Abigail Alliance] (2) brought suit to enjoin the FDA from enforcing its current policy banning the use of post-Phase I investigational drugs by terminally ill patients excluded from Phase II clinical trials. (3) The Court of Appeals for the D.C. Circuit recognized a constitutional substantive due process right "to access potentially life-sustaining medication where there are no alternative government-approved treatment options." (4) After concluding that the right asserted by Abigail Alliance merits due process protection, the court remanded the case to the district court to determine whether the FDA's current policy withstands the application of the rigorous strict scrutiny review, essentially, to determine whether the policy is narrowly tailored to serve a compelling governmental interest. (5)

    This article analyzes whether the government has a compelling interest in preventing mentally competent, terminally ill patients from accessing post-Phase I drugs. Part II reviews the history of FDA drug regulation and summarizes current law pertaining to the drug approval process. Part III considers whether, in light of the constitutional right recognized by the D.C. Circuit, the government's interest in public health can validate restrictions on drug access for terminally ill patients. More specifically, Part III examines whether such restrictions can be justified either by the benefits they confer upon terminally ill patients themselves, or by the benefits they confer upon society at large. Finally, Part IV concludes by finding that both of these justifications fail, thereby undermining the government's claim to a compelling interest in restricted drug access for this population.

  2. FDA DRUG APPROVAL PROCESS

    1. History

      Federal regulation of drugs began with the Pure Food and Drug Act [hereinafter PFDA]. (6) Enacted in 1906 in response to criticism of widespread food and drug impurities, (7) this legislation established liability for the manufacture of adulterated (8) or misbranded (9) drugs by requiring manufacturers to monitor their products for strength, quality, and purity, (10) and to provide complete and accurate labeling of drug contents. (11) However, the PFDA failed to set forth standards or specific methods of pre-market testing that would prevent adulteration, or to provide any mechanism for centralized regulatory approval of new drugs. (12)

      The 1937 Elixir Sulfanilamide tragedy (13) spurred Congress to take a more significant step toward a pre-market drug approval system. Towards that end, Congress passed the Food, Drug, and Cosmetic Act [hereinafter FDCA], which required safety testing and government approval of new drugs before commercial marketing. (14) Under the provisions of the FDCA, prospective manufacturers were required to file applications for the sale of new drugs with the Secretary of Agriculture, describing drug components and composition, methods of production control, and proposed labeling language. (15) The FDCA also required applicants to provide investigational safety reports and samples of the drugs under consideration. (16) Unless the Secretary of Agriculture rejected or postponed consideration of the application within sixty days of filing, default approval was conferred by statute. (17)

      The final step in the evolution of modern drug regulation occurred in response to the thalidomide tragedy, (18) after which Congress enacted the Kefauver-Harris Amendments [hereinafter 1962 Amendments]. (19) The 1962 Amendments required more rigorous pre-approval drug testing than was required under the original FDCA, instituting a series of clinical testing "phases" that comPrise the norm under current law. (20) At present, the initial steps in obtaining FDA approval entail laboratory and animal testing to determine whether a drug is sufficiently safe and promising to justify human experimentation. (21) Using evidence gathered in these preliminary tests to support safety and efficacy claims, the drug sponsor files an Investigational New Drug (IND) application, seeking FDA authorization to begin the process of testing on humans. (22)

    2. The Clinical Trial System

      Although clinical trials are both expensive and time consuming, the process of submitting an IND for clinical testing approval is relatively straightforward. An IND application notifies the FDA that a company is about to initiate clinical trials and permits the FDA to conduct an initial assessment of the value of those trials on the basis of the information provided by the applicant. (23) If the IND application is granted, the sponsor is permitted to begin clinical experimentation on human subjects, (24) which is mandatory for final FDA approval of a drug, (25)

      A three-phase process of testing on human subjects remains the FDA standard. (26) Phase I consists of initial safety testing, during which a relatively small sample of healthy, asymptomatic subjects receive the drug and are monitored for signs that the drug may be unsafe for humans. (27) If the results of Phase I indicate that the drug may be safe, the sponsor proceeds to Phase II, during which both the safety and efficacy of the drug are examined through controlled experimentation upon a larger sample of symptomatic subjects. (28) If the results from Phase II are promising, a much larger sample is used in Phase III to further assess safety and efficacy. (29)

      If the results of clinical testing are promising through Phase III, the IND sponsor may decide to continue seeking FDA approval by submitting a New Drug Application (NDA), which provides the FDA with information that includes the data collected and analyzed during experimentation. (30) Within 180 days, the FDA must approve the application or notify the applicant of the opportunity to request a hearing on the merits of the application. (31) If granted, FDA approval is promised upon proof of the safety and efficacy of the drug when used for the "on-label" purposes stipulated by the drug's sponsor. (32)

      C Expanded Access Programs

      In an effort to balance the government's interest in drug safety and efficacy with terminally ill patients' interest in gaining rapid access to promising therapies, the FDA has carved out several exceptions to the clinical trial testing process described above. (33) These exceptions fall into one of two categories: expanded access (whereby some patients gain access to drugs before approval) and expedited review (in which the approval process itself is hastened or truncated). (34) Because drugs in the latter category receive FDA approval before market entry, only the expanded access exceptions are relevant to the analysis of a pre-approval right to access; thus, the exceptions in this category are outlined below.

      1. Treatment IND

        In 1987, the FDA enacted "Treatment IND" provisions that formalized expanded access procedures for patients suffering from serious or life-threatening diseases in the absence of satisfactory approved alternative drugs or therapies. (35) Under these provisions, a drug manufacturer may apply to the FDA for permission to distribute a promising investigational therapy prior to final approval if:

        (i) The drug is intended to treat a serious or immediately life-threatening disease; (ii) there is no comparable or satisfactory alternative drug or other therapy available to treat that stage of the disease in the intended patient population; (iii) the drug is under investigation in a controlled clinical trial, under an IND in effect for the trial, or all clinical trials have been completed; and (iv) the sponsor of the controlled clinical trial is actively pursuing marketing approval of the investigational drug with due diligence. (36) Treatment INDs are a viable option for serious diseases during or after Phase III investigation and in some situations may be granted as early as Phase II. (37) For immediately life-threatening diseases, Treatment INDs are available "[e]arlier than Phase Ill, but...

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