Causality assessment of adverse effects: when is re-challenge ethically acceptable?
Drug Saf
; 24(11): 793-9, 2001.
Article
en En
| MEDLINE
| ID: mdl-11665867
ABSTRACT
One of the most difficult tasks in the evaluation of a medicine is whether it causes a particular rare and unusual (idiosyncratic) adverse effect. Such causality assessments are sometimes done by drug de-challenge and re-challenge. When the adverse effect is potentially serious, there is clearly an important decision to be made as to whether the re-challenge is justifiable and hence ethical. The recent controversy about the potential cardiotoxicity of fexofenadine, the fatalities associated with penicillin re-challenge and the fatalities associated with abacavir re-challenge highlight some of the potential serious risks of drug re-challenge. The associated important ethical issues are discussed. In particular, there is the need to ensure respect for the patient and to consider the scientific and social value of the re-challenge. A framework for evaluating and assessing the appropriateness of a particular drug re-challenge is proposed in the light of recent as well as long-standing discussions of drug re-challenge, patient informed consent and the ethics of human experimentation, in general. It is suggested that a drug re-challenge should be approached with the same rigour and standards of documentation as are currently required of clinical trials. Given the potential conflicts of interest inherent with any drug study, it is argued that the safeguards, as may be provided by scrutiny by an ethics committee, are necessary for a drug re-challenge. For the investigator contemplating the conduct of a drug re-challenge we would recommend the following (i) a careful risk-benefit assessment as part of the decision-making process; (ii) careful scientific preparation, including appropriate expert support and emergency back-up facilities, if re-challenge is deemed necessary; (iii) the writing of a detailed protocol for independent approval and for safeguarding all concerned; and (iv) meticulous record keeping.
Palabras clave
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Hipersensibilidad a las Drogas
/
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos
/
Ética Médica
Tipo de estudio:
Etiology_studies
/
Guideline
/
Prognostic_studies
Límite:
Humans
País/Región como asunto:
Europa
Idioma:
En
Revista:
Drug Saf
Asunto de la revista:
TERAPIA POR MEDICAMENTOS
/
TOXICOLOGIA
Año:
2001
Tipo del documento:
Article
País de afiliación:
Reino Unido