Compassionate Use: A Story of Ethics and Science in the Development of a New Drug
Abstract
This history chronicles the unusual development of the antiviral drug ganciclovir. The first compound with activity against human cytomegalovirus (CMV), ganciclovir was so clearly efficacious that a placebo-controlled clinical trial could not ethically be done, and the FDA rejected the first application to market the drug. Used to treat a blinding eye infection in patients with AIDS, the story of ganciclovir paralleled the spread of the AIDS epidemic. Both ganciclovir and AIDS caught the federal government off guard. Caught in a Catch-22 situation, the pharmaceutical company developing ganciclovir gave the drug away free for five years under compassionate use guidelines. The problems encountered in the development of ganciclovir provide guidance on how future drugs to treat life-threatening diseases can be developed.
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Many highly beneficial drugs would have failed animal testing and would never have been brought to market, except that they were developed before animal testing was required.
“However, many highly beneficial drugs would have failed animal testing and would never have been brought to market, except that they were developed before animal testing was required (38).”
From Limitations of Animal Studies for Predicting Toxicity in Clinical Trials (2019) · cites this paper as [38]
Ganciclovir was refused licensure by the FDA due to lack of animal studies despite compassionate human use demonstrating efficacy and safety in treating AIDS-related cytomegalovirus retinitis in more patients than generally required for a phase I trial.
“Compassionate human use of ganciclovir demonstrated efficacy and safety in treating acquired immunodeficiency syndrome–related cytomegalovirus retinitis in more human patients than would generally be required for a phase I clinical trial, but the FDA refused to license it due to lack of animal studies.”
From Limitations of Animal Studies for Predicting Toxicity in Clinical Trials (2019) · cites this paper as [42]
Lack of animal tests caused deleterious delays in critical drug approvals.
“Lack of animal tests has also caused deleterious delays in critical drug approvals.”
From Limitations of Animal Studies for Predicting Toxicity in Clinical Trials (2019) · cites this paper as [42]
Ganciclovir was delayed for more than a year due to lack of animal studies and finally approved after a 4-year delay.
“but the FDA delayed clinical trials for more than a year due to lack of animal studies. The drug was finally approved after a 4-year delay (42).”
From Limitations of Animal Studies for Predicting Toxicity in Clinical Trials (2019) · cites this paper as [42]
There is data suggesting that in vitro testing and other methods are significantly faster and less expensive than animal models.
“however, there is data suggesting that in vitro testing and other methods are significantly faster and less expensive than animal models (42,44).”
From Limitations of Animal Studies for Predicting Toxicity in Clinical Trials (2019) · cites this paper as [42]
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Limitations of Animal Studies for Predicting Toxicity in Clinical Trials
Van Norman, G. A. (2019) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2019.10.008 · Cited by 709 · see citing works
“A comprehensive study of the accuracy, LR, and costs of alternative testing methods compared with animal toxicity testing has not been published; however, there is data suggesting that in vitro testing and other methods are significantly faster and less expensive than animal models (42,44).”
BackgroundMethod
- Authors
- Buhles, W. C.
- Corresponding author
- Buhles, William C.
- Venue
- Perspectives in Biology and Medicine
- Publisher
- Project MUSE
- Published
- 2011-06
- Volume
- 54
- Issue
- 3
- Pages
- 304-315
- ISSN
- 0031-5982 (ISSN-L)
- 1529-8795
- OpenAlex
- W1967744790
- Cited by
- 24
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 2
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Perspectives in biology and medicine (publishedVersion)
- PubMed (publishedVersion)
- Project Muse (Johns Hopkins University) (submittedVersion)
- DigitalGeorgetown (Georgetown University Library) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Biomedical Ethics and Regulation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmaceutical industry and healthcare
- Keywords
- ganciclovir, compassionate use, antiviral agents, human cytomegalovirus, AIDS, drug approval, FDA, clinical trial ethics, drug pricing
- MeSH terms
- Acquired Immunodeficiency Syndrome, Antiviral Agents, Cytomegalovirus Infections, Cytomegalovirus, Drug Industry, HIV, Humans, Retinitis, United States, Ganciclovir, Drug Approval, History, 20th Century, Drug Dosage Calculations, Compassionate Use Trials
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