OFF-LABEL DRUG-USE IN HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE

We wished to determine the extent to which drugs used to treat HIV dis ease and its clinical manifestations are prescribed fur conditions oth er than those listed on the U.S. Food and Drug Administration's approv ed drug label, how such ''off-label'' use varies by patient characteri stics and type of HIV-related medical condition, and the extent to whi ch physicians alter the way they treat HIV-related conditions because of reimbursement problems associated with off-label drug use. We surve yed 1,530 primary care providers for people with HIV disease between F ebruary and May 1993, A three-part survey instrument was used to obtai n data on the drugs prescribed for the last three patients with HIV di sease treated by the provider, the preferred choice of therapy for 32 specific HIV-related conditions, and the extent to which providers fac ed reimbursement problems regarding the use of drugs for off-label ind ications, Three drug compendia were used as cited sources of off-label drug uses. In all, 387 (32%) evaluable surveys were returned, yieldin g data on 1.148 patients. The majority; (81%) of patients received at least one drug off-label, and almost half (40%) of all reported drug t herapy was off-label. Most off-label drug use was for treatment and pr evention of HIV-related opportunistic infections, which frequently rep resented the community standard of practice (e.g., trimethoprim/sulfam ethoxazole for prevention of Pneumocystis carinii pneumonia), or the d e facto standard of practice when no licensed therapies were available (e.g., drugs for treatment of Mycobacterium avium complex, MAC). More than 75% of off-label usage was cited in at least one of the three au thoritative medical compendia. The use of drugs for off-label indicati ons in HIV care is common and frequently represents community standard s of care. Reliance on drug compendia for support of off-label drug us e accounts for the majority of such uses, although many legitimate off -label uses may not be included because of compendia publication lag. The prevalence of off-label drug use in routine clinical practice and the development of newer and more costly drugs for treatment of HIV an d its medical complications argues for the articulation of an explicit national reimbursement policy for off-label uses of prescription drug s so that medically appropriate therapies will be available to those w ith insurance in a rational, consistent way.