title: The Northwick Park tragedy--protecting healthy volunteers in future first-in-man trials.
abstract: The development of potentially powerful drugs which may become effective in the treatment for disorders currently difficult to manage presents the pharmaceutical industry and the scientific community with a major challenge. Such drugs with novel modes of action and the capacity to modify the body's immune system could also be very toxic. The possibility became a tragic reality on March 13th 2006 when TGN1412 was given to six healthy volunteers at Northwick Park hospital. All six became seriously ill. Fortunately none died but some were left with serious residual defects. The British Secretary of State for Health set up an Expert Scientific Group to investigate this tragic event. The report had to make recommendations designed to prevent a recurrence whilst not unduly delaying or discouraging the development of new drugs designed to treat cancers and other serious disorders. They made 22 recommendations. The drug TGN1412 had been shown to be well tolerated by non-human primates. A recent report on non-human primates in research recommended their continued use in some forms of research, for example on brain disorders. However, they also recommended that non-human primates should be used sparingly and only when justified scientifically. Their treatment should be optimal and research on them should be restricted to selected centres of expertise. The tragedy at Northwick Park should encourage the Pharmaceutical Industry to rethink their use of non-human primates in drug toxicity testing and hopefully to reduce their use and treat them better.
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: T
authors.initials: T
authors.lastname: Dowsing
authors.forename: M J
authors.initials: MJ
authors.lastname: Kendall
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D002986:Clinical Trials as Topic / Q000941:ethics / Q000379:methods* / Q000592:standards; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced* / Q000517:prevention & control; D017408:Guidelines as Topic / Q000592:standards; D006761:Hospitals; D006801:Humans; D007275:Injections, Intravenous; D008131:London; D008252:Macaca fascicularis; D008297:Male; D023421:Models, Animal; D018570:Risk Assessment; D012952:Societies / Q000592:standards
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C509303:TGN-1412