Access to Unapproved Drugs

The commentary by Simon and Green¹ in this issue of the Journal addresses the very complex issue of an individual patient's right to access pharmacotherapy that is not Food and Drug Administration (FDA)-approved for the management of a life-threatening disease. This is far from a black and white issue and it is very polarizing. Some ardent patients’ rights advocates demand that seriously ill patients be granted access to any pharmacotherapy they wish whether or not the drugs have undergone the legally mandated governmental review for safety and efficacy. Strict adherents of the Food Drug and Cosmetic Act (FDC Act) and its numerous amendments—the principal laws upon which drug regulation in the United States are based—demand that physicians only have access for routine patient care to drugs that have been approved through the rigorous, multiphase, and many-year-long drug review and licensing process.

The Journal is grateful to Editorial Board member Lee Simon, a former FDA Division Director and Harvard Medical School faculty member, and his colleague Allen Green, a physician, scientist, and attorney, who have so thoughtfully addressed this complex issue. Their commentary outlines the applicable law and the Code of Federal Regulations provisions that both limit and permit emergency access to investigational drugs. They also describe the process though which a physician may obtain access to an unapproved investigational drug for an individual patient.

A “New Drug” is a substance that is not approved by the FDA for human use. It is generally not legal for a clinician to use a “New Drug” in patient care except within Investigational Review Board (IRB)-approved and monitored clinical studies of the agent after the FDA has licensed investigational use of the substance through issuance of an Investigational New Drug Exemption (IND). An IND is the legally required, FDA-granted permission for a clinician to use a New Drug in such a study. Public demand for access to investigational new drugs when an approved treatment for the indication is lacking has recently led to the creation of Individual Patient IND.

Knowledgeable persons can argue both in favor of and against access to investigational new drugs for individual patients through this new process. Potential benefits to individuals from the use of these unapproved new drugs must be weighed in the context of potential risks to society due to adverse events resulting from early access to the drugs. An important confound in this debate is who will pay for these unapproved—and often extremely expensive—agents.

This issue is far from resolved. The federal courts have written conflicting rulings and the FDA is in the middle of the firestorm. Emotions are strong, and legitimate arguments can be made on both sides of the debate. Pain clinicians often are asked to opine on this issue due to profound symptom control implications.

We hope that the thoughtful analysis of this issue by Simon and Green will allow our readers to better understand this complex issue and help them form more informed opinions on it.

Psychopathology and Pain

This issue of the Journal introduces a new feature entitled Psychopathology and Pain to help meet an important and generally unmet need in the pain literature. Every pain clinician knows that anxiety, depression, personality disorders, bipolar disorder, and a range of additional psychological disorders are not uncommon among chronic pain patients. Anxiety about acute pain due to impending surgery or following major trauma is more the rule than the exception. And in end-of-life care, anxiety, affective disorders, and other psychological confounds are often the norm.

Difficult to manage pain not infrequently is complicated by, or even due largely to, psychopathology. Yet the majority of clinicians who manage chronic and acute pain have limited training and experience in managing most psychological disorders. Indeed, pain specialist physicians who have American Board of Medical Specialties–added qualifications (board certification) in pain medicine recognize the need to refer many pain patients to mental health professionals for assessment and treatment, often more commonly than their colleagues who lack that additional training and certification.

Most pain management is provided in the primary care setting. Pharmacotherapy is by far the most common treatment modality used in that environment. Commonly, primary care clinicians use antianxiety, antidepressant, and other psychopharmacotherapeutic agents in the management of pain patients.

When primary care–based interventions are not adequate, patients often are referred to interdisciplinary pain programs. An integral part of most such programs is mental health professional evaluation and care in addition to medical and physical interventions. Pain patient evaluations by psychologists, psychiatrists, and other mental health professionals often reveal psychopathology that confounds pain management. Not uncommonly, psychiatric pharmacotherapy, e.g., initiation of an antidepressant, is needed before a patient can engage effectively in medical, physical, and behavioral therapies. But all depression does not respond in the same way to antidepressant therapy. And all antidepressant drugs are not appropriate for all depressed patients. Anxiety is not a single disorder and antianxiety pharmacotherapy is not appropriate for all anxiety states. Furthermore, some psychiatric drugs exacerbate patients’ other symptoms and some cause detrimental drug interactions

To help pain clinicians better understand the range of psychopathology that impact pain management, this series will explore these issues in depth. The introductory paper that appears in this Journal issue describes how mental health professionals evaluate their patients’ psychopathology and briefly describes three psychological disorders commonly seen in chronic pain patients. Future papers will differentiate and address management of a range of psychopathology.

We are grateful to Journal Editorial Board member Kenneth L. Kirsh, PhD, a practicing clinical psychologist at The Pain Treatment Center of the Bluegrass in Lexington Kentucky and a faculty member at the University of Kentucky College of Pharmacy for coordinating and editing this new feature. Dr. Kirsh is an experienced pain clinician and investigator. His perspective, and those of his mental health professional and other colleagues who will collaborate with him on this new feature, should help all of us improve our care of patients in pain.

It is not coincidental that the Editorial Board of this Journal includes three psychologists and two psychiatrists. Psychopathology is perhaps the least well understood and managed dimension of many pain patients’ care. We hope that this new Journal feature will help pain clinicians more effectively address their patients psychological care.

Arthur G. Lipman, PharmD

Editor

Notes

* Federal regulatory definition of a “New Drug”: (1) Any drug—the composition of which is such that this drug is not generally recognized, among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs, as safe and effective for use under the conditions presented, recommended, or suggested in the labeling thereof; or (2) Any drug—the composition of which is such that this drug, as a result of investigations to determine its safety and effectiveness for use under such conditions, has become so recognized, but which has not, otherwise than in such investigations, been used to a material extent or for a material time under such conditions.