What Makes Clinical Research Ethical
TL;DR: 7 requirements are proposed that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies and are universal, although they must be adapted to the health, economic, cultural, and technological conditions in which clinical research is conducted.
Abstract: Many believe that informed consent makes clinical research ethical. However, informed consent is neither necessary nor sufficient for ethical clinical research. Drawing on the basic philosophies underlying major codes, declarations, and other documents relevant to research with human subjects, we propose 7 requirements that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies: (1) value-enhancements of health or knowledge must be derived from the research; (2) scientific validity-the research must be methodologically rigorous; (3) fair subject selection-scientific objectives, not vulnerability or privilege, and the potential for and distribution of risks and benefits, should determine communities selected as study sites and the inclusion criteria for individual subjects; (4) favorable risk-benefit ratio-within the context of standard clinical practice and the research protocol, risks must be minimized, potential benefits enhanced, and the potential benefits to individuals and knowledge gained for society must outweigh the risks; (5) independent review-unaffiliated individuals must review the research and approve, amend, or terminate it; (6) informed consent-individuals should be informed about the research and provide their voluntary consent; and (7) respect for enrolled subjects-subjects should have their privacy protected, the opportunity to withdraw, and their well-being monitored. Fulfilling all 7 requirements is necessary and sufficient to make clinical research ethical. These requirements are universal, although they must be adapted to the health, economic, cultural, and technological conditions in which clinical research is conducted. JAMA. 2000;283:2701-2711.
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TL;DR: The results indicated that underrepresented populations face numerous barriers to participation in cancer‐related trials, and the available evidence had limitations in quality regarding representativeness, justification of study methods, the reliability and validity of data‐collection methods, potential for bias, and data analysis.
Abstract: Racial and ethnic minorities, older adults, rural residents, and individuals of low socioeconomic status are underrepresented among participants in cancer-related trials. The authors conducted a systematic review to determine the barriers to participation of underrepresented populations in cancer-related trials. Their search included English-language publications that reported original data on the recruitment of underrepresented groups to cancer treatment or prevention trials between 1966 and December 2005 in multiple electronic databases. They also hand-searched titles in 34 journals from January 2003 to December 2005 and they examined reference lists for eligible articles. Titles and abstracts were reviewed to identify relevant studies. Data on barriers to participation were synthesized both qualitatively and based on statistically significant associations with trial enrollment. Of 5257 studies that were cited, 65 studies were eligible for inclusion in the current analysis, including 46 studies on recruitment into cancer therapeutic trials, 15 studies on recruitment into prevention trials, and 4 studies on recruitment into both prevention and treatment trials. Numerous factors were reported as barriers to participation in cancer-related trials. However, only 20 of the studies reported statistically significant associations between hypothesized barriers and enrollment. The available evidence had limitations in quality regarding representativeness, justification of study methods, the reliability and validity of data-collection methods, potential for bias, and data analysis. The results indicated that underrepresented populations face numerous barriers to participation in cancer-related trials. The current systematic review highlighting the literature on recruitment of underrepresented populations to cancer trials and may be used as the evidence base toward developing an agenda for etiologic and intervention research to reduce the disparities in participation in cancer-related trials.
865 citations
TL;DR: This work applies a previously proposed ethical framework for clinical research within developed countries to developing countries explicating a previously implicit requirement for collaboration and proposes specific and practical benchmarks to guide researchers and research-ethics committees in assessing how well the enumerated ethical principles have been fulfilled in particular cases.
Abstract: In recent years there has been substantial debate about the ethics of research in developing countries. In general the controversies have centered on 3 issues: first the standard of care that should be used in research in developing countries; second the “reasonable availability” of interventions that are proven to be useful during the course of research trials; and third the quality of informed consent. The persistence of controversies on such issues reflects in part the fact that existing ethical guidelines can be interpreted in multiple ways are sometimes contradictory or rely on unstated yet controversial ethical principles. To provide unified and consistent ethical guidance we apply a previously proposed ethical framework for clinical research within developed countries to developing countries explicating a previously implicit requirement for collaboration. More importantly we propose specific and practical benchmarks to guide researchers and research-ethics committees in assessing how well the enumerated ethical principles have been fulfilled in particular cases. (excerpt)
842 citations
Cites background from "What Makes Clinical Research Ethica..."
...Science and ethics do not conflict; valid science is an ethical requirement [25, 37]....
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...An ethical framework for multinational research should minimize the possibilities of exploitation [25]....
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...Finally, review must be independent and competent [25]....
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...The ethical conduct of clinical research does not end when informed consent is obtained [25]....
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...Previously, we delineated a framework for ethical research that included 7 principles [25]....
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TL;DR: Recommendations of a two-year project group funded by NIH to study how to manageIFs in genetic and genomic research, as well as imaging research are reported, which conclude that researchers have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB and research participants.
Abstract: Researchers, institutional review boards (IRBs), participants in human subjects research, and their families face an important but largely neglected problem — how should incidental findings (IFs) be managed in human subjects research. If researchers unexpectedly stumble upon information of potential health or reproductive significance, should they seek expert evaluation, contact the participant’s physician, tell the research participant, or respond with some combination? What should consent forms and the entire consent process say about how IFs will be handled in research? What should IRBs require?
636 citations
TL;DR: In multivariate analysis, increased knowledge was associated with college education, speaking only English at home, use of the US National Cancer Institute consent form template, not signing the consent form at initial discussion, presence of a nurse, and careful reading of the consent forms.
611 citations
TL;DR: It is concluded that underpowered trials are ethical in only 2 situations: small trials of interventions for rare diseases in which investigators document explicit plans for including their results with those of similar trials in a prospective meta-analysis, and early-phase trials in the development of drugs or devices, provided they are adequately powered for defined purposes other than randomized treatment comparisons.
Abstract: Despite long-standing critiques of the conduct of underpowered clinical
trials, the practice not only remains widespread, but also has garnered increasing
support Patients and healthy volunteers continue to participate in research
that may be of limited clinical value, and authors recently have offered 2
related arguments to support the validity and value of underpowered clinical
trials: that meta-analysis may "save" small studies by providing a means to
combine the results with those of other similar studies to enable estimates
of an intervention's efficacy, and that although small studies may not provide
a good basis for testing hypotheses, they may provide valuable estimates of
treatment effects using confidence intervals In this article, we examine
these arguments in light of the distinctive moral issues associated with the
conduct of underpowered trials, the disclosures that are owed to potential
participants in underpowered trials so they may make autonomous enrollment
decisions, and the circumstances in which the prospects for future meta-analyses
may justify individually underpowered trials We conclude that underpowered
trials are ethical in only 2 situations: small trials of interventions for
rare diseases in which investigators document explicit plans for including
their results with those of similar trials in a prospective meta-analysis,
and early-phase trials in the development of drugs or devices, provided they
are adequately powered for defined purposes other than randomized treatment
comparisons In both cases, investigators must inform prospective subjects
that their participation may only indirectly contribute to future health care
benefits
463 citations
References
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TL;DR: The principles of biomedical and Islamic medical ethics and an interfaith perspective on end-of-life issues and three cases to exemplify some of the conflicts in ethical decision-making are discussed.
Abstract: Morality and ethical theory types of ethical theory the principle of respect for autonomy the principle of nonmaleficence the principle of beneficence the principle of justice professional-patient relationships ideals, virtues and conscientiousness.
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"What Makes Clinical Research Ethica..." refers background in this paper
...Respect for potential and enrolled subjects Respect for subjects by (1) permitting withdrawal from the research; (2) protecting privacy through confidentiality; ( 3 ) informing subjects of newly discovered risks or benefits; (4) informing subjects of results of clinical research; (5) maintaining welfare of subjects Respect for subject autonomy and welfare Scientific knowledge; ethical and legal knowledge; knowledge of particular subject ......
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...Drawing on the basic philosophies underlying major codes, declarations, and other documents relevant to research with human subjects, we propose 7 requirements that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies: (1) value— enhancements of health or knowledge must be derived from the research; (2) scientific validity—the research must be methodologically rigorous; ( 3 ) fair subject ......
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TL;DR: Faden, R.R., and Beauchamp, T.L. as mentioned in this paper present a history and theory of informed consent in the context of consent and informed consent theory.
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2,091 citations