Establishing risk of human experimentation with drugs: lessons from TGN1412
2006; Elsevier BV; Volume: 368; Issue: 9544 Linguagem: Inglês
10.1016/s0140-6736(06)69562-7
ISSN1474-547X
Autores Tópico(s)Pharmaceutical studies and practices
ResumoAdministration of a chemical or biological compound to a human being is never without risk. Although knowledge about risks increases during the development process, risks are still present even when a substance is marketed. 1 Bresalier RS Sandler RS Quan H et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005; 352: 1092-1102 Crossref PubMed Scopus (2336) Google Scholar Particular care is necessary when a new drug is given to healthy volunteers without previous human testing. General principles for such research have been laid down in guidelines as early as 1983, and these were the basis for many current regulations. 2 Council for International Organizations of Medical SciencesSafety requirements for the first use of new drugs and diagnostic agents in man: a review of safety issues in early clinical trials of drugs. Council for International Organizations of Medical Sciences, Geneva1983 Google Scholar Most drugs at that time were small molecules with fairly well characterised, classic, pharmacological mechanisms. Proposed primary objectives for studies in healthy people were therefore to show pharmacological action in man and the dose (or concentration) response curve. This approach was judged safe and was lent support by findings of available surveys. 3 Orme M Harry J Routledge P Hobson S Healthy volunteer studies in Great Britain: the results of a survey into 12 months activity in this field. Br J Clin Pharmacol. 1989; 27: 125-133 Crossref PubMed Scopus (35) Google Scholar , 4 Zarafonetis CJ Riley Jr, PA Willis 3rd, PW et al. Clinically significant adverse effects in a phase 1 testing program. Clin Pharmacol Ther. 1978; 24: 127-132 PubMed Google Scholar Over time, the main objectives for these trials changed—perhaps owing to the perceived safety of new traditional (small-molecule) medicines—to general tolerance and safety.
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