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Therapeutic optimism in the consent forms of phase 1 gene transfer trials: an empirical analysis
  1. J Kimmelman,
  2. N Palmour
  1. Clinical Trials Research Group, Biomedical Ethics Unit, Faculty of Medicine/McGill University, Montreal, Quebec, Canada
  1. Correspondence to:
 J Kimmelman
 Clinical Trials Research Group, Biomedical Ethics Unit, Faculty of Medicine/McGill University, 3647 Peel Street, Montreal, Quebec H3A 1X1, Canada;


Background: “Therapeutic misconception” arises when human subjects interpret a clinical trial as aimed primarily at therapy rather than producing knowledge. Therapeutic misconceptions may be more prevalent in trials enrolling gravely ill subjects or involving novel and well publicised investigational agents.

Objective: To examine the extent to which investigators express therapeutic optimism in phase 1 human gene transfer consent documents, whether highly active gene transfer researchers are more prone to expressing therapeutic optimism, and whether consent forms have grown more optimistic in their descriptions of personal benefit over the last decade.

Design: Content analysis was performed on 277 consent documents to measure the number of sentences describing possibility of benefit, terminology used for experimental agents, the proportion of statements describing personal versus societal benefits, and whether investigators attempted to thwart therapeutic misconceptions.

Results: Consent forms generally used therapeutic terminology to describe study agents, devoted more sentences to describing possible personal benefits than to describing benefits to society, and infrequently explained that a particular benefit was unlikely. Consent documents used by highly active gene transfer researchers tended to portray significantly greater optimism about personal benefit than less active investigators, though they were also significantly more cautious with agent terminology. Finally, therapeutic optimism expressed in consent forms has declined over the past decade.

Conclusions: Consent documents used in phase 1 gene transfer trials, although increasingly attentive to possible therapeutic misconceptions, are inappropriately optimistic about direct benefits of trial participation. Such optimism is expressed more emphatically in trials involving highly active gene transfer researchers as principal investigators.

  • HGT, human gene transfer
  • IRB, institutional review board
  • OBA, Office of Biotechnology Activities
  • PI, principal investigator
  • RAC, Recombinant DNA Advisory Committee
  • benefit
  • consent documents
  • ethics
  • gene therapy
  • human gene transfer
  • informed consent
  • non-financial conflict of interest
  • therapeutic misconception

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  • This work was funded by the Canadian Institutes of Health Research and the Stem Cell Genomics and Therapeutics Network.


    The author wishes to direct the interested reader to two related studies that were published since the acceptance of our manuscript: Henderson GE, Davis AM, King M, et al. Uncertain benefit: investigators’ news and communicationsin early phase gene transfer trials. Mol Ther2004;:–31 and Kim NM, Henderson GE, Churchill LR, et al. Consent forms and therapeutic misconception. The example of gene transfer research. IRB2005;:–8.

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