Legal and Risk Management Concerns Relating to the Use of non-FDA Approved Drugs in the Practice of Psychiatry

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Access to Unapproved Drugs Under FDA Authority

Typically, a patient has access to unapproved drugs by participating in a clinical trial. The FDA drug approval process requires three phases of clinical testing in humans. Phase 1 investigates the dangers of drugs in humans at different doses. Phase 2 seeks to determine if a drug actually works, as well as its short-term side effects, if any. If the drug proves safe and possibly effective, Phase 3 examines long-term side effects, effectiveness, and optimal dosage.¹³ However, participation in a clinical trial does not assure that a patient will receive the drug under investigation instead of a placebo.

The FDA has responded to criticism by establishing initiatives to speed up access to unapproved drugs in some circumstances. In response to concerns that the FDA's lengthy drug approval process prevented patients from having access to beneficial, yet unapproved, new drug therapies, changes were made in 1987 to FDA regulations allowing patients earlier access to unapproved new drugs through the "Treatment Investigational New Drug" process.¹⁴ Under the FDA's "Treatment Investigational New Drug" (Treatment IND) regulations, an individual "licensed medical practitioner" may apply for early access to an unapproved drug for patient treatment. The agency permits sponsors of Investigational drugs to provide them to doctors for use in treating patients who are not involved in controlled clinical trials. Treatment IND regulations highlight the fact that the Investigational (unapproved) drug is being disbursed to treat certain seriously ill patients as opposed to gaining information about the drug's safety and effectiveness, as would be the goal of a clinical trial. The regulations state that unapproved drugs may be made available under a treatment IND during Phase 2 or Phase 3 investigations, or after clinical trials have been completed. A treatment IND can begin 30 days after the application is received by the FDA or earlier if the licensed medical practitioner is notified of FDA approval of the treatment IND application.¹⁵ To apply, the psychiatrist should request in writing a treatment IND packet, which will come with instructions for completion. The address is: FDA/Office of Information Resources Management, FDA Forms Management Officer, 5600 Fishers Lane, Room 16B-26, Rockville, MD 20857 or via e-mail at esands@bangate.fda.gov. The phone number is 301-827-1480 and the fax is 301-594-0060. For questions about the process or for assistance in completion of an IND application form contact the FDA Public Affairs Office at 301-827-4573.

The criteria for issuing a treatment IND are: "(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 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."16 A licensed practitioner who submits a treatment IND is a "sponsor-investigator and is responsible for meeting all applicable sponsor and investigator responsibilities."17 These responsibilities include complying with FDA regulations related to prospective Institutional Review Board (IRB) review and informed consent. These regulations are found in the Code of Federal Regulations (21 C.F.R. Part 50 and Part 56) and pertain to the protection of human subjects participating in studies involving unapproved drugs. They are intended to provide protection to the rights of human subjects, to insure that legally effective informed consent is obtained, and that human subjects are properly informed of the significant aspects of the study. The Code of Federal Regulations may be accessed on the Internet at http://www.access.gpo.gov/nara/cfr/index.html.

A psychiatrist considering applying for a treatment IND may have concerns that psychiatric conditions will not meet the serious or life-threatening disease requirement. However, the FDA has reported that a drug to treat severe obsessive-compulsive disorder received treatment IND status in 1994.18

There are a variety of sources that provide information about current clinical trials with Investigational new drugs, including: 1) drug companies/manufacturers; 2) university hospitals or teaching hospitals who conduct clinical research; 3) National Institutes of Health and the National Institute of Mental Health; 4) CenterWatch, Inc., a multimedia publishing company in Boston, MA, available at http://www.centerwatch.com or (617) 247-2327, which provides listings of clinical trials and other information for patients and professionals; and 5) F-D-C Reports, at 1-800-332-2181 or http://www.fdcreports.com, which publishes information about FDA approvals, biomedical research news, health policy, NIH news and information, etc.

Professional Liability Insurance Coverage Issues

Any adverse event caused either by the use of a non-approved drug or as a result in the disruption of a patient's supply can expose the psychiatrist to a claim for damages. Generally, insurance companies do not provide coverage for claims relating to alleged criminal or wrongful acts.19

In response to a growing concern among its participants, the APA-endorsed Professional Liability Insurance Program has reviewed the relevant policy language, along with certain pertinent FDA regulations. By complying with the FDA application process for treatment with Investigational new drugs and by providing The Program Manager with documentation of FDA approval for the use of unapproved drugs, the physician may avoid jeopardizing professional liability coverage related to the treatment of patients with unapproved drugs. The APA-endorsed Professional Liability Insurance Program requires that the insured physician submit all documentation relating to the FDA approval for use of unapproved drugs under a treatment IND, including any treatment protocols, and any amendments or modifications to approval at the time they may occur. The Underwriting Department at PRMS, Inc. (The Program Manager) will maintain this documentation, because such documentation will be critical to a determination of coverage if a claim arises out of the treatment of patients by the prescription of unapproved drugs under a treatment IND. By following this procedure of obtaining FDA approval for a treatment IND, and by providing all required documentation to PRMS, Inc. before undertaking to treat a patient with an unapproved drug, a psychiatrist may well avoid the unpleasant prospect of having to personally pay to defend and indemnify against a malpractice claim arising out of such treatment.

Reducing Potential Liability Through Risk Management

After FDA approval is obtained for use of unapproved drugs, the following risk management advice should be followed to reduce the risk of professional liability.

1). It is recommended that all available approved treatment modalities be exhausted first. The patient's history of illness and response to all pharmacological interventions and medical treatments should be clearly documented. The documentation should show that all approved drugs and/or treatments have been considered and rejected as inappropriate for the patient, and that the patient has been advised of this. The documentation should include the patient's response or lack of response to available, approved drugs. The basis for the clinical decision-making related to using unapproved drugs under a FDA authorized protocol must be clearly enumerated.

2.) The physician should consider sending the patient for a second opinion or a consult by another doctor with the appropriate expertise. It is recommended that the patient be informed that he or she has the option of a second opinion before considering use of an unapproved drug. The physician should document that the patient has been informed of this option. The results of any consultation or second opinion should be included in the patient's record.

3.) A thorough informed consent discussion should be held with the patient and the patient's family if appropriate. The informed consent process should be in compliance with the FDA regulations governing informed consent. The elements of informed consent include, but are not limited to, the following: 1) the patient must understand that the proposed treatment is experimental and must receive an explanation of the purpose of the Investigational drug and its expected benefits; 2) the patient should know that participation is voluntary and that a decision on the part of the patient to terminate use of the drug will not affect the patient's care or treatment; and 3) a clear description of the risks and benefits of participation and alternatives to participation should be provided. The informed consent discussion should be documented in the patient's record and a signed consent form, in compliance with Institutional Review Board (IRB) requirements, must be in the record. Remember that informed consent is a process, and continuous documentation should record the patient/psychiatrist dialogue regarding discussions about the medication, the patient's response to the drug, and any information and actions of the psychiatrist in response.

4.) The manner in which patient information will be handled should be discussed, including measures to be taken to assure confidentiality. The duty to protect patient confidentiality does not change when a patient is involved in clinical trials or a treatment IND. A recommendation that the patient consult personal legal counsel for clarification of any questions or legal issues may be appropriate.

5.) If the patient consents to treatment under a treatment IND, all clinical protocols must be scrupulously followed and documented carefully. For example, all blood work and other laboratory testing and patient monitoring requirements that are part of the treatment protocol must be followed and documented. During the initial stage of the drug treatment the patient may need more frequent follow-up visits.

6.) There should be a treatment plan that is documented and agreed to by the patient. It should include actions to be taken by both the patient and the physician in the event there is an adverse reaction to the treatment.

Conclusion

Use of unapproved drugs presents serious clinical and legal risks for patients and physicians. It is advised that access to unapproved drugs should only occur through FDA authorized and regulated procedures. Complying with the treatment IND process reduces clinical risks and may provide a means for professional liability insurance coverage to be available should a claim arise out of the treatment of a patient with unapproved drugs. Psychiatrists considering the use of unapproved drugs by means other than the FDA authorized methods should obtain the advice of personal counsel before proceeding.

This article was written by Susan M. King, JD, with the research and assistance of the staff of the Risk Management Department of Professional Risk Management Services, Inc., The Program Manager for the APA-endorsed Professional Liability Insurance Program. Ms. King is a partner in the law firm of Kelner & King, LLP, located in Hollywood, Florida. The author gratefully thanks everyone who participated in helping this article to be written.

References:
1. As used in this article, the term "unapproved drug" means any drug that does not have final FDA approval.
2. 21 U.S.C. section 301 et seq. (1988 & Supp. V 1993).
3. 21 C.F.R. Part 314.
4. 21 U.S.C. section 355 (1988).
5. Loosening FDA's Drug Certification Monopoly: Implications for Tort Law and Consumer Welfare, Geo. Mason U.L. Rev. (Spring 1996) at 134.
6. FDA Home Page, The Beginnings: Laboratory and Animal Studies, http://www.fda.gov./fdac/special/newdrug/begin.html, 3/31/98.
7. Legal Overview of FDA Authority Over Imports, 49 Food & Drug L.J. 525 (1994) at 399.
8. FDA Regulatory Procedures Manual, Chapter 9 "Coverage of Personal Importations", August, 1997.
9. Id. at 409.
10. Sifre v. Robles, 917 R. Supp. 133 (1996).
11. Regulatory Procedures Manual, supra, at 409.
12. FDA Authority Over Imports, supra, at 398.
13. 21 C.F.R. section 312.12 (1995).
14. The Food and Drug Administration's Early Access and Fast Track Approval Initiatives: How Have They Worked? 50 Food & Drug L.J. 503 (1995) at 332. Other FDA initiatives, which provide broader and earlier access to promising Investigational therapies, are available to patients with AIDS and HIV-related illnesses and to cancer patients.
15. 21 C.F.R. section 312.34 (1995).
16. 21 C.F.R. section 312.34(b)(1) (1995).
17. 21 C.F.R. section 312.35(2) (1995).
18. FDA Home Page, http://www.fda.gov/fdac/special/newdrug/speeding.html, 3/31/98.
19. Most professional liability insurance policies exclude from coverage any claim arising out of or in connection with violations of law, or criminal or deliberately wrongful acts committed by the Insured.

This article appeared in the Spring 1998 edition of The Program's risk management newsletter Rx for Risk. For reprint information please call (800) 245-3333, ext. 393.

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