title: [Drug trials in humans. Risks in the light of the London catastrophe].
abstract: London's first-in-man drug trial with the monoclonal anti-CD28 antibody TGN1412 used for the treatment of oncological and autoimmune diseases resulted in a disaster with life-threatening adverse events in the volunteers triggered by an unexpected cytokine storm. Potential mistakes and consequences from this trial are highlighted in the general context of drug development and its risks. Risks in drug testing are not only found for high risk substances, such as TGN1412, or in the critical first-in-man phase, but can sometimes be detected only in later phases of the clinical testing, such as the phase 3 submission studies, or even after market authorization, as for example was the case in the cyclooxygenase-2-inhibitor rofecoxib (Vioxx) used for the treatment of rheumatic diseases and acute pain. Regulatory requirements to minimize risks in drug trials, however, have improved substantially over the last decades. Moreover, in light of the London incident these are being continuously modified with great diligence.
authors.affiliation: Zentrum Klinische Studien, Universitätsklinikum Freiburg, Elsässer Strasse 2, 79110 Freiburg, Germany. andreas.otte@uniklinik-freiburg.de
authors.forename: A
authors.initials: A
authors.lastname: Otte
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D002985:Clinical Protocols; D002986:Clinical Trials as Topic / Q000379:methods / Q000401:mortality*; D004341:Drug Evaluation / Q000379:methods / Q000401:mortality*; D006801:Humans; D008131:London / Q000453:epidemiology; D009026:Mortality; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C509303:TGN-1412