Ethical dilemmas in continuing a zidovudine trial after early termination of similar trials.
Ethical dilemmas caused by external events and an interim subset analysis raised concerns about continuing a long-term VA clinical trial comparing early with later zidovudine therapy for symptomatic human immunodeficiency virus (HIV) infection. The first external event was the early termination of other, apparently similar, trials conducted by the AIDS Clinical Trials Group (ACTG) and the announced clear benefits for the zidovudine-treated patients. Interim analysis of the VA trial at this time did not show similar benefits. Subset analyses were performed to explore factors that might explain the different results. These suggested a difference in response to zidovudine in white and minority groups. The Data Monitoring Board and a special advisory panel reviewed these data and concluded that, since the VA results were neutral overall and the subset analyses based on small numbers, the trial should continue. By conference call, the study cochairmen and biostatistician discussed this decision with study personnel without revealing interim results, and study personnel passed the information on to patients at the participating centers. The second event was in March 1990, when the Food and Drug Administration (FDA) approved earlier use of zidovudine, which applied to patients still in the VA trial. Patients were asked to reaffirm their participation by signing a new informed consent that explained the findings reported by the ACTG, the FDA-approved revised recommendations, and the rationale for continuation of the VA trial. The consent form emphasized that continued masked therapy was optional and that unmasked treatment and follow-up would be provided to patients requesting it. Seventy-four percent of the participants chose to continue masked therapy. We conclude that when new external data are announced, informed participation in a long-term clinical trial may require a revised consent form and that it is ethical and practical to present this without disclosure of interim study results.
Simberkoff
M S
MS
Infectious Diseases Section, NYVAMC, NY 10010.
Hartigan
P M
PM
Hamilton
J D
JD
Deykin
D
D
Gail
M
M
Bartlett
J G
JG
Feorino
P
P
Redfield
R
R
Roberts
R
R
Collins
D
D
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002986:Clinical Trials as Topic / Q000331:legislation & jurisprudence; D032962:Consent Forms; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004992:Ethics, Medical; D035082:Federal Government; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007258:Informed Consent / Q000331:legislation & jurisprudence; D007958:Leukocyte Count / Q000187:drug effects; D018570:Risk Assessment; D036302:Therapeutic Human Experimentation; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects
D015215:Zidovudine