Jan-Feb 05 IRB.qxd E T H I C S HUMAN RESEARCH & IRB Appelbaum and colleaguesfirst described the “thera-peutic misconception” in 1982.1 There has been much dis- cussion since then about whether and why...

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Should IRBs be concerned about the possibility of the therapeutic misconception? Should research participation offer direct benefit to subjects? Why or why not?




Jan-Feb 05 IRB.qxd E T H I C S HUMAN RESEARCH & IRB Appelbaum and colleaguesfirst described the “thera-peutic misconception” in 1982.1 There has been much dis- cussion since then about whether and why some patients who enter clinical trials confuse research with treatment and overestimate the nature or likelihood of benefit to them from research in which they enroll, and about whether investi- gators share in or contribute to any misunderstanding.2 The therapeutic misconception has been examined empirically in surveys and inter- views,3 some of which focus on phase I trials,4 and in one pub- lished examination of consent forms for phase I oncology research.5 Thus, Appelbaum and colleagues’ original focus on whether research subjects under- stood how study design elements like randomization and placebo arms could affect them has expanded to encompass factors characteristic of early-phase trials, such as translation from laboratory and animal studies to human trials and the implications of dose escala- tion design. However, there has been relatively little discussion of these and other ethical and design questions raised by early-phase clinical research.6 To examine how consent forms for early-phase trials address scien- tific uncertainty and describe potential benefits, we analyzed 321 consent forms for gene transfer research, 99% of which were early-phase (phase I, I/II, or II) tri- als, and 69% of which were oncol- ogy trials. Our goal was to assess how consent form language might promote or reduce the therapeutic misconception (including misesti- mation7 of potential benefit) in early-phase research. We chose to examine how the prospect of benefit is described in gene transfer research for several reasons. This small but rapidly growing field of clinical research is based on what seems to be com- pelling scientific logic: since genes direct vital cellular functions, then inadequate cellular functioning should be treatable if new copies of healthy genes are added.8 Just 15 years old, gene transfer research holds out both great promise and great uncertainty; commands con- siderable public attention, both positive and negative; and exempli- fies the ethical challenges of disclo- sure in the face of unknowns, uncertainties, and the high failure JA N UA RY-FE B RUA RY 2005 • VO L U M E 27, NU M B E R 1 Consent Forms and the Therapeutic Misconception: The Example of Gene Transfer Research by Nancy M.P. King, Gail E. Henderson, Larry R. Churchill, Arlene M. Davis, Sara Chandros Hull, Daniel K. Nelson, P. Christy Parham-Vetter, Barbra Bluestone Rothschild, Michele M. Easter, and Benjamin S. Wilfond 1 The Quality of Informed Consent in a Clinical Research Study in Thailand by Christine Pace, Ezekiel J. Emanuel, Theshinee Chuenyam, Chris Duncombe, Judith D. Bebchuk, David Wendler, Jorge A. Tavel, Laura A. McNay, Praphan Phanuphak, Heidi P. Forster, and Christine Grady, for the ESPRIT Group 9 BOOK REVIEW: Case Studies in Biomedical Research Ethics by Jacquelyn Slomka 18 ANNOTATIONS 19 INSTRUCTIONS FOR AUTHORS 20 A PUBLICATION OF THE HASTINGS CENTER Consent Forms and the Therapeutic Misconception: The Example of Gene Transfer Research BY NANCY M.P. KING, GAIL E. HENDERSON, LARRY R. CHURCHILL, ARLENE M. DAVIS, SARA CHANDROS HULL, DANIEL K. NELSON, P. CHRISTY PARHAM-VETTER, BARBRA BLUESTONE ROTHSCHILD, MICHELE M. EASTER, AND BENJAMIN S. WILFOND Nancy M.P. King, Gail E. Henderson, Larry R. Churchill, Arlene M. Davis, Sara Chandros Hull, Daniel K. Nelson, P. Christy Parham-Vetter, Barbra Bluestone Rothschild, Michele M. Easter, and Benjamin S. Wilfond, “Consent Forms and the Therapeutic Misconception: The Example of Gene Transfer Research,” IRB: Ethics & Human Research 27, No. 1 (2005): 1-8. JA N UA RY-FE B RUA RY 2005 IRB: ET H I C S & HU M A N RE S E A RC H potential for early-phase research.9 Gene transfer research also receives extra guidance and oversight;10 its consent forms undergo greater scrutiny and must conform to addi- tional standards. This increased attention might be expected to improve the discussion of possible benefits to potential subjects. Defining Benefits in Clinical Research To characterize the potential ben-efits described in early-phase gene transfer research consent forms, we applied the following def- initions. Failure to distinguish among the types of benefits in con- sent forms may both reflect and contribute to conceptual confu- sion.11 First, benefits to subjects (benefits from study participation) should be distinguished from benefits to socie- ty (future benefits to science or to future patients from research results). Because benefits to socie- ty—described in federal research regulations as contributions to gen- eralizable knowledge—can only be realized in the future, they should be readily distinguishable from benefits to subjects. However, when consent forms describe the ultimate aim of the line of research or the mecha- nism of action of the experimental intervention without differentiating these from potential benefits for subjects in the current trial, it may be difficult to distinguish between benefits to subjects and benefits to society. The following example illus- trates this blurring: “Gene therapy works by using a virus vector to carry the new gene into the patient’s cells. Once there, the new gene makes the protein that patients like you lack. The investigators hope that gene therapy will be an effective treatment for your disease.” Benefits to subjects are further divided into two types: direct bene- fits from receipt of the experimental intervention, and inclusion benefits (also called collateral or indirect benefits), which result from partici- pating in a study regardless of whether the subject receives the experimental intervention. The potential direct benefits that may be described in a consent form (Table 1) depend on the nature of the experimental intervention and the subjects’ disease or condition. Inclusion benefits need not be so study-specific; descriptions in con- sent forms can encompass such diverse items as free goods or servic- es provided as an enrollment incen- tive; diagnostic testing and standard treatments provided on-study at no cost to subjects; the opportunity to be monitored closely by disease experts; and sometimes, potential psychological benefits from “doing everything possible” for oneself and/or for others. Although direct and inclusion benefits are quite dif- ferent, they are not always distin- guished in consent forms. A consent form statement discussing potential benefits to the subject from “study participation” may refer to direct benefits, inclusion benefits, or both, and it may be difficult to determine which type is meant. Study Methods We obtained copies of all con-sent forms and portions of protocols for human gene transfer studies dating from 1990 through August 2000 that are on file and publicly available at the Office of Biotechnology Activities (OBA) of the National Institutes of Health (NIH). All documents were redacted before analysis to delete information that could identify individuals, spon- sors, and institutions. Gene transfer studies were excluded from the analysis if their files were confiden- tial, unavailable, or incomplete. Studies using healthy volunteers as subjects were also excluded, as were gene marking studies, which provide data on the feasibility and efficiency of gene transfer using only genes with no therapeutic potential. The resulting total of 321 consent forms represents over 90% of non-mark- ing gene transfer studies submitted to OBA during the first 10 years of human gene transfer research. Institutional Review Boards (IRBs) at the University of North Carolina at Chapel Hill and the National Human Genome Research Institute approved the study. All consent forms and protocol materials were assessed with a 94-question instrument developed iteratively using practice protocols.12 Eight investigators working in teams of two coded the materials, with one 2 Table 1. Nature of Direct Benefit in Consent Forms Nature Category Definition Consent Form Examples Contentless no nature information you may or may not benefit; personal benefit is not guaranteed Surrogate Endpoint laboratory measurement tumor shrinkage, that stands in statistically decrease in PSA, for a clinical endpoint increased % Factor IX in blood, decreased CD4+ count Clinical Endpoint specific benefit that can live longer, fewer bleeds, be felt or experienced by cure, remission, less subjects leg pain, fewer lung infections, improved breathing IRB: ET H I C S & HU M A N RE S E A RC H JA N UA RY-FE B RUA RY 2005 3 investigator (NK) serving as a mem- ber of every team. Each team recon- ciled disagreements, and Kappa scores were calculated for each item. Kappa scores measure the amount of agreement beyond what would be observed by chance (measured as 0); perfect agreement is measured as 1. All scores for data presented here were in the moderate range (.41 to .60).13 Descriptions of Potential Benefit. We looked for descriptions of direct, inclusion, and societal ben- efits in the five major sections of the consent form: Background/Purpose, Procedures, Risks, Benefits, and Alternatives. We examined each description of potential direct benefit according to the following dimen- sions: nature, magnitude, duration, and likelihood. We divided descrip- tions of the nature of potential direct benefits into contentless (no descrip- tion, e.g., “benefit”), surrogate end- points (measurements substituted for experiences, e.g., “tumor response”), and clinical endpoints (specific and experienceable, e.g., “live longer”)14 (Table 1). We divided statements about the likelihood of potential direct benefits into likely, unlikely, and indeterminate (probability state- ments that could not be further spec- ified, e.g., “may or may not”; “you might”; “cannot be predicted”). We also recorded when no mention was made of benefit in a section, when there was no such section, and when the section said, “You will not bene- fit.” We coded mentions of surrogate and clinical endpoints only when coders agreed that the endpoint was described or offered as a benefit. For example, “your tumors may shrink” and “we will check to see if your tumors shrink” were coded as surro- gate endpoints offered as potential direct benefits, whereas “any changes in tumor size during the study will be recorded” was not. Statements like “may help cause remission of your disease” were coded as clinical endpoints offered as direct benefits, whereas statements like “we hope that this research is the first step toward a future cure for this disease” were not. Language Use. We also col- lected information about the use of research and treatment terminology in the consent form, such as whether treatment terms were used to describe the entire study, and what terms were used to describe subjects in conspicuous places, such as the study title at the beginning of the consent form or the signature line at the end. In addition, we examined language use in more detail in 20% of the 321 consent forms (N=68). Consent forms were ordered by date and a systematic sample of every fifth consent form was drawn. In this sample, we counted the terms that, from context, clearly referred to subjects, investigators, and experi- mental gene
Answered Same DayFeb 09, 2022

Answer To: Jan-Feb 05 IRB.qxd E T H I C S HUMAN RESEARCH & IRB Appelbaum and colleaguesfirst described the...

Bhawna answered on Feb 10 2022
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Should IRBs be concerned about the possibility of the therapeutic misconception? Should research participation offer direct benefit to subjects? Why or why not?
Misconception refers to any wrong belief about a concept,
the same misconception about any research is described as therapeutic misconceptions. Therapeutic misconception occurs when the subject fails to appreciate the difference between clinical research and an ordinary treatment. The concept of therapeutic misconception was defined in the 1980s when a participant's belief was identified where she thought that the research is being done for her benefit only. However, she was not aware that the research is taking place at a large scale and this will be used to develop different therapeutics (Appelbaum at al.,2004). The misconception about therapeutics can arise from both sides, the researcher as well as the participants. Sometimes the research can cause several research-oriented mistakes that may compromise the overall research. The most common issues that are concerned with therapeutic misconceptions are ethical issues, these will be discussed briefly later (Henderson et al., 2007).
The Institutional Review Board (IRB) is a review committee that has the responsibility of approving or disapproving a proposal before the project is submitted to the funding agency. The main focus of the Institutional review board is to take care of human rights and prevent them from any type of exploitation during the research. The IRB follows the federal regulations as well as ethical interests to protect human rights. The IRB has all the rights reserved to approve or disapprove the project on these ethical grounds.
There are several factors that can unintentionally increase the chance of therapeutic misconceptions. The factors which can increase the chances of therapeutic misconceptions are (i) similar care in research and real treatment, sometimes the research is about care interventions, and in these cases, the participants are not able to distinguish as being used for research or being actually treated in real. (ii) the researchers are not able to provide clarity to the participants about the study and hence the...
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