Further lessons from the TGN1412 tragedy

Goodyear, Michael D.

doi:10.1136/bmj.38929.647662.80

Cited by 23 publications

(8 citation statements)

References 6 publications

(4 reference statements)

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“…The testing of new pharmaceuticals on humans is approved by ethics committees based on the assumption that the inherent risks of trial participation are balanced by the benefit of new scientific knowledge for society. If this knowledge from Phase I remains hidden, then any potential risk incurred by trial participation is excessive and could endanger human lives [ 23 ]. Although Phase I trials are usually safe [ 24 ] with very few deaths and severe adverse events (incidence of related severe adverse events of 0.2% over a 2-y period among 15,386 participants), adverse events from Phase I studies are known to be rarely published [ 25 ], which means that this knowledge is unavailable to other researchers who may unknowingly conduct harmful trials on similar interventions.…”

Section: Discussionmentioning

confidence: 99%

Inadequate Dissemination of Phase I Trials: A Retrospective Cohort Study

2009

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BackgroundDrug development is ideally a logical sequence in which information from small early studies (Phase I) is subsequently used to inform and plan larger, more definitive studies (Phases II–IV). Phase I trials are unique because they generally provide the first evaluation of new drugs in humans. The conduct and dissemination of Phase I trials have not previously been empirically evaluated. Our objective was to describe the initiation, completion, and publication of Phase I trials in comparison with Phase II–IV trials.Methods and FindingsWe reviewed a cohort of all protocols approved by a sample of ethics committees in France from January 1, 1994 to December 31, 1994. The comparison of 140 Phase I trials with 304 Phase II–IV trials, showed that Phase I studies were more likely to be initiated (133/140 [95%] versus 269/304 [88%]), more likely to be completed (127/133 [95%] versus 218/269 [81%]), and more likely to produce confirmatory results (71/83 [86%] versus 125/175 [71%]) than Phase II–IV trials. Publication was less frequent for Phase I studies (21/127 [17%] versus 93/218 [43%]), even if only accounting for studies providing confirmatory results (18/71 [25%] versus 79/125 [63%]).ConclusionsThe initiation, completion, and publications of Phase I trials are different from those of other studies. Moreover, the results of these trials should be published in order to ensure the integrity of the overall body of scientific knowledge, and ultimately the safety of future trial participants and patients.

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Section: Discussionmentioning

confidence: 99%

Inadequate Dissemination of Phase I Trials: A Retrospective Cohort Study

2009

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“…Toward this end, expert scientific group under Professor Gordon Duff was formed which further investigated the biological and ethical concerns which may have resulted in the disastrous aftermath. [ 12 ] Just after few minutes of drug infusion, all six human volunteers started suffering severe cytokine release syndrome leading to sever inflammation. [ 13 ] Similar effects were observed in small number of patients treated with rituximab, muromonab-CD3, and alemtuzumab antibodies.…”

Section: The First Dose Disastermentioning

confidence: 99%

TGN1412: From Discovery to Disaster

Attarwala

2010

Journal of Young Pharmacists

203

112

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After a drug is confirmed as safe and efficacious in preclinical studies, it is tested in healthy human volunteers for first in man trials. In 2006, a phase I clinical study was conducted for a CD28 superagonist antibody TGN1412 in six human volunteers. After very first infusion of a dose 500 times smaller than that found safe in animal studies, all six human volunteers faced life-threatening conditions involving multiorgan failure for which they were moved to intensive care unit. After this particular incident, a lot was changed over how first in man trials are approved by regulatory authorities and the way clinical trials are conducted. This review primarily deals with preclinical studies conducted by TeGenero, results of which encouraged them to test the antibody on human subjects, reasons why this drug failed in human trial and aftermath of this drug trial. In addition, another drug—Fialuridine which failed in phase 2 clinical trial leading to death of five human subjects is briefly reviewed.

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“…In The TeGenero (TGM1412) incident some healthy volunteers were seriously injured during a first-in-man study of a biological agent 10. Media reports after the event discussed the levels of payment that these subjects received and whether they compromised their understanding of the potential side effects 11.…”

Section: Inducement and Consentmentioning

confidence: 99%

Payment for participation in research: a pursuit for the poor?

Stones

McMillan

2009

J Med Ethics

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Poor people predominate as a subgroup of those who take part in healthy volunteer research. They are subjected to minimised but unknown risks and unpleasant burdens so that the safety of new medicines can be evaluated. This is prima facie unfair especially given that the poor are often unable to access expensive medicines. Although participants in this kind of research often do receive compensation for their time, these payments are usually capped at a very low level. This paper defends a version of a reimbursement model for the payment of research subjects. This model is practical, would benefit those without an income who take part in research, and would make it possible for those in regular work to take part in phase 1 research.

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Further lessons from the TGN1412 tragedy

Cited by 23 publications

References 6 publications

Inadequate Dissemination of Phase I Trials: A Retrospective Cohort Study

Inadequate Dissemination of Phase I Trials: A Retrospective Cohort Study

TGN1412: From Discovery to Disaster

Payment for participation in research: a pursuit for the poor?

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