The last two decades have witnessed a crescendo of allegations that clinical translation is rife with waste and inefficiency. Patient advocates argue that excessively demanding regulations delay access to life‐saving drugs, research funders claim that too much basic science languishes in academic laboratories, journal editors allege that biased reporting squanders public investment in biomedical research, and drug companies (and their critics) argue that far too much is expended in pharmaceutical development.But how should stakeholders evaluate the efficiency of translation and proposed (...) reforms to drug development? Effective reforms require an accurate model of the systems they aspire to improve—their components, their proper functions, and their pathologies. However, there is currently no explicit and well‐developed model of translation for evaluating such criticisms.In what follows, we offer an explicit model of clinical translation. Many discussions of clinical translation and its pathologies presume that its main output is tangible: new drugs, vaccines, devices, and diagnostics. We disagree. We argue that the principal output of clinical translation is information—in particular, information about the coordinated set of materials, practices, and constraints needed to safely unlock the therapeutic or preventive activities of drugs, biologics, and diagnostics. To develop this information calls for a process far different from a simple linear progression of clinical trials; it requires exploratory sampling of many different elements in this set. Our model points to some limitations and liabilities of influential proposals for reforming research. It also reveals some underrecognized opportunities for improving the efficiency of clinical translation. (shrink)

Trials with highly unfavourable risk–benefit ratios for participants, like HIV cure trials, raise questions about the quality of the consent of research participants. Why, it may be asked, would a person with HIV who is doing well on antiretroviral therapy be willing to jeopardise his health by enrolling in such a trial? We distinguish three concerns: first, how information is communicated to potential participants; second, participants’ motivations for enrolling in potentially high risk research with no prospect of direct benefit; and (...) third, participants’ understanding of the details of the trials in which they enrol. We argue that the communication concern is relevant to the validity of informed consent and the quality of decision making, that the motivation concern does not identify a genuine problem with either the validity of consent or the quality of decision making and that the understanding concern may not be relevant to the validity of consent but is relevant to the quality of decision making. In doing so, we derive guidance points for researchers recruiting and enrolling participants into their HIV cure trials, as well as the research ethics committees reviewing proposed studies. (shrink)

Ocular gene transfer clinical trials are raising hopes for blindness treatments and attracting media attention. News media provide an accessible health information source for patients and the public, but are often criticized for overemphasizing benefits and underplaying risks of novel biomedical interventions. Overly optimistic portrayals of unproven interventions may influence public and patient expectations; the latter may cause patients to downplay risks and over-emphasize benefits, with implications for informed consent for clinical trials. We analyze the news media communications landscape about (...) ocular gene transfer and make recommendations for improving communications between clinicians and potential trial participants in light of media coverage. (shrink)

Ethical concerns have been raised about the quality of informed consent by participants in phase 1 oncology trials. Interview surveys indicate that substantial proportions of trial participants do not understand the purpose of these trials—evaluating toxicity and dosing for subsequent efficacy studies—and overestimate the prospect of therapeutic benefit that they offer. In this article we argue that although these data suggest the desirability of enhancing the process of information disclosure and assessment of comprehension of the implications of study participation, they (...) do not necessarily invalidate consent by phase 1 trial participants. (shrink)

Many commentators have expressed concern that large investments in biomedical research over the past two decades have not been translated effectively into clinical applications. In its Critical Path Report, the Food and Drug Administration characterized the problem as a “technological disconnect between discovery and the product development process,” and documented that the number of investigational new drugs submitted to the agency had declined “significantly” since 2000. Along a similar vein, another study found that only five of 101 basic science studies (...) showing significant therapeutic promise were successfully translated into clinical applications.This perceived translational lag is stimulating a shift toward human testing of study interventions earlier in the drug development process. One indication of this trend is a recent guidance encouraging sponsors to pursue human “exploratory” studies before embarking on phase I trials. (shrink)

Background: Therapeutic misconception, the misunderstanding of differences between research and clinical care, is widely prevalent among non-incarcerated trial participants. However, little attention has been paid to its presence among individuals who participate in research while incarcerated. Methods: This study examined the extent to which 72 incarcerated individuals may experience therapeutic misconception about their participation in one of six clinical trials, and its correlation with participant characteristics and potential influences on research participation. Results: On average, participants endorsed 70% of items suggestive (...) of therapeutic misconception. The tendency toward therapeutic misconception was significantly higher among African Americans and Latinos compared to Whites, among older and less educated participants, and among enrollment in a substance-abuse-related trial; it was also correlated with a belief that the trial was the only way to obtain needed treatment. Conclusions: Therapeutic misconception may be particularly high among select incarcerated individuals and is associated with a perceived lack of treatment options. Further examination of therapeutic misconception among incarcerated research participants is needed. (shrink)

BackgroundStudies have shown that research participants fail to appreciate the difference between research and medical care, labeling such phenomenon as a "therapeutic misconception" (TM). Since research activity involving human participants is increasing in the Middle East, qualitative research investigating aspects of TM is warranted. Our objective was to assess for the existence of therapeutic misconception amongst Egyptians.MethodsStudy Tool: We developed a semi-structured interview guide to elicit the knowledge, attitudes, and perspectives of Egyptians regarding medical research.Setting: We recruited individuals from the (...) outpatient settings (public and private) at Ain Shams University in Cairo, Egypt.Analysis: Interviews were taped, transcribed, and translated. We analyzed the content of the transcribed text to identify the presence of a TM, defined in one of two ways: TM1 = inaccurate beliefs about how individualized care can be compromised by the procedures in the research and TM2 = inaccurate appraisal of benefit obtained from the research study.ResultsOur findings showed that a majority of participants (11/15) expressed inaccurate beliefs regarding the degree with which individualized care will be maintained in the research setting (TM1) and a smaller number of participants (5/15) manifested an unreasonable belief in the likelihood of benefits to be obtained from a research study (TM2). A total of 12 of the 15 participants were judged to have expressed a TM on either one of these bases.ConclusionThe presence of TM is not uncommon amongst Egyptian individuals. We recommend further qualitative studies investigating aspects of TM involving a larger sample size distinguished by different types of illnesses and socio-economic variables, as well as those who have and have not participated in clinical research. (shrink)

Evidence suggests that research participants often fail to recall much of the information provided during the informed consent process. This study was conducted to determine the proportion of consent information recalled by drug court participants following a structured informed consent procedure and the neuropsychological factors that were related to recall. Eighty-five participants completed a standard informed consent procedure to participate in an ongoing research study, followed by a 17-item consent quiz and a brief neuropsychological battery 2 weeks later. Participants performed (...) within the normal range on most of the neuropsychological measures, although roughly one third showed deficits on measures of executive functioning. Participants failed to recall over 65% of the consent information within 2 weeks of entering the study, and their recall was significantly correlated with verbal IQ, drug problem severity, reading ability, memory, and attention. These factors may be useful in determining whether research participants require enhanced consent procedures. (shrink)