Institutional review boards and investigators are used to talking about risks of harm. Both low risks of great harm and high risks of small harm must be disclosed to prospective subjects and should be explained and categorized in ways that help potential subjects to understand and weigh them appropriately. Everyone on an IRB has probably spent time at meetings arguing over whether a three-page bulleted list of risk description is helpful or overkill for prospective subjects. Yet only a small fraction (...) of all the time and attention lavished on risk disclosure has been devoted to discussing whether and when potential benefit to subjects can reasonably be claimed and, if so, how it should be described in the consent form and process.Traditionally, IRBs and regulators have worked to ensure that clear lines can be drawn between research that, by definition, carries no potential for direct benefit — because it uses healthy volunteers or because it is not foreseeably focused on the development of treatments — and research that does have the development of effective treatments as its goal. (shrink)

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. (shrink)

In March 1996, the General Accounting Office (GAO) issued the reportScientific Research: Continued Vigilance Critical to Protecting Human Subjects.It stated that “an inherent conflict of interest exists when physician-researchers include their patients in research protocols. If the physicians do not clearly distinguish between research and treatment in their attempt to inform subjects, the possible benefits of a study can be overemphasized and the risks minimized.” The report also acknowledged that “the line between research and treatment is not always cleartoclinicians. Controversy (...) exists regarding whether certain medical procedures should be categorized as research.”This problem currently plagues gene transfer research. A few months prior to the GAO report, an ad hoc committee appointed by National Institutes of Health (NIH) Director Harold Varmus expressed similar concerns in its assessment of NIH investment in research on gene therapy. (shrink)

In March 1996, the General Accounting Office (GAO) issued the reportScientific Research: Continued Vigilance Critical to Protecting Human Subjects.It stated that “an inherent conflict of interest exists when physician-researchers include their patients in research protocols. If the physicians do not clearly distinguish between research and treatment in their attempt to inform subjects, the possible benefits of a study can be overemphasized and the risks minimized.” The report also acknowledged that “the line between research and treatment is not always cleartoclinicians. Controversy (...) exists regarding whether certain medical procedures should be categorized as research.”This problem currently plagues gene transfer research. A few months prior to the GAO report, an ad hoc committee appointed by National Institutes of Health (NIH) Director Harold Varmus expressed similar concerns in its assessment of NIH investment in research on gene therapy. (shrink)

In March 1996, the General Accounting Office issued the report Scientific Research: Continued Vigilance Critical to Protecting Human Subjects. It stated that “an inherent conflict of interest exists when physician-researchers include their patients in research protocols. If the physicians do not clearly distinguish between research and treatment in their attempt to inform subjects, the possible benefits of a study can be overemphasized and the risks minimized.” The report also acknowledged that “the line between research and treatment is not always clear (...) to clinicians. Controversy exists regarding whether certain medical procedures should be categorized as research.”This problem currently plagues gene transfer research. A few months prior to the GAO report, an ad hoc committee appointed by National Institutes of Health Director Harold Varmus expressed similar concerns in its assessment of NIH investment in research on gene therapy. (shrink)