Protection Of Human Research Subjects Research Articles

How Well Are We Protecting Human Research Subjects?

Protecting human research subjects is an ethical mandate for all contemporary research involving human subjects. From 1974 to 1999, we had the institutional review board (IRB) system and the Common Rule, but realized that in addition to IRBs, investigators, institutions, sponsors of research, research participants, and the government, all share responsibilities in protecting human research subjects. Starting 2000, institutions established human research protection programs to ensure the rights and welfare of research participants and to meet human research ethical and regulatory requirements. Some institutions had their human research protection programs further accredited to ensure rigorous standards for quality and protection. In 2018, the Common Rule was extensively revised to modernize the regulations by enhancing protections and reducing burden for researchers. However, throughout these periods, we did not know how well we were protecting human research subjects, because we did not know how to measure human research subject protections. With the publication of human research subject protections performance metrics in 2023, it becomes possible for the first time to assess quantitatively how well we are protecting human research subjects. Research institutions can now monitor the effectiveness of their human research protection programs and identify areas of vulnerability for quality improvement. We should also be able to determine how well human research protection programs are doing in protecting human research subjects; determine whether external accreditation improves human research subject protections and whether the revised Common Rule in fact leads to enhanced protections; and identify prospectively which procedures or interventions can enhance human research subject protections.

Ethics Review of Biomedical Research in Uzbekistan: Policy and Program Gaps.

We describe the national health research ethics review system of Uzbekistan and identify policy and program gaps that impede the protection of human research subjects. We find that the National Ethic Committee (NEC), functioning at the national level, is solely responsible for conducting research ethics review. There is little evidence that regional ethics committees work as intended, and there is no research ethics review at medical institutes and research centers even though they conduct CDTs (clinical drug trials). There is no national policy for the ethical review of non-clinical trials. We recommend the establishment of institutional review boards (IRBs) at medical institutes and research centers while at the same time building capacity at the national level to oversee and support the research ethics review system of the entire country.

Considering Risks to Researchers and Staff in Low-Resource Settings during Public Health Crises: A Proposed Conceptual Model

Human subjects research protections have historically focused on mitigating risk of harm and promoting benefits for research participants. In many low-resource settings (LRS), complex and often severe challenges in daily living, poverty, geopolitical uprisings, sociopolitical, economic, and climate crises increase the burdens of even minimal risk research. While there has been important work to explore the scope of ethical responsibilities of researchers and research teams to respond to these wider challenges and hidden burdens in global health research, less attention has been given to the ethical dilemmas and risk experienced by frontline researcher staff as they perform research-related activities in LRS. Risks such as job insecurity, moral distress, infection, or physical harm can be exacerbated during public health crises, as recently highlighted by the COVID-19 pandemic. We highlight the layers of risk research staff face in LRS and present a conceptual model to characterize drivers of this risk, with particular attention to public health crises. A framework by which funders, institutions, principal investigators, and/or research team leaders can systematically consider these additional layers of risk to researchers and frontline staff is an important and needed addition to routine research proposals and protocol review.

Physician Perceptions of Pediatric Palliative Care for Children with Cancer in Latin America

Background: The World Health Organization (WHO) designates early integration of palliative care as an ethical responsibility in the management of children with serious illness. While structural barriers may influence provision of pediatric palliative care (PPC) for children with cancer in resource-limited settings, underlying physician perceptions also impede early integration of PPC within cancer care. Methods: The Assessing Doctor’s Attitudes on Palliative Treatment (ADAPT) survey was developed for physicians who care for children with cancer and initially distributed in Eurasia. In this study, the survey was modified for use in Latin America including translation into Spanish and adapted for cultural context. Descriptive statistics were used to summarize the data, along with univariate and multivariable analyses of factors impacting knowledge and comfort in PPC practice. Open-ended questions were analyzed qualitatively to supplement the quantitative data. Findings: A total of ­­­­874 physicians from 17 countries completed the survey. Most physicians (56%) had no formal PPC training and 35% had no access to PPC experts for consultation. On average, providers’ perspectives on PPC were aligned with WHO guidance (­­­83% alignment, range 24% - 100%). However, only 50% of respondents felt comfortable addressing physical symptoms, 34% felt comfortable addressing emotional symptoms, and 25% felt comfortable addressing grief and bereavement for the patient’s family. Provider specialty and previous palliative care training were significantly associated with WHO alignment and physician comfort in addressing patient needs. Ninety-six percent of survey participants desired further education and training in PPC. Interpretation: Despite perspectives aligning with WHO guidance, this study identified opportunities for improving physician training in symptom management and emotional support for children with cancer and their families. These findings will inform the development of targeted interventions to enhance PPC education and improve the quality of care for children with cancer in Latin America. Funding Information: American Lebanese Syrian Associated Charities. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The Office of Human Subjects Research Protections and Institutional Review Board at St. Jude Children’s Research Hospital (Memphis, TN, USA) approved this study as exempt research. Additional local approvals were obtained as needed.

Facilitating Timely Institutional Review Board Review: Common Issues and Recommendations.

Review of clinical research by institutional review boards (IRBs) is integral to the protection of human subjects and necessary for the conduct of legal and ethical research. Because such review is time and resource intensive, it is critical to identify common issues that contribute to delayed review and approval of research. Hence, the aim of this quality improvement project was to identify factors associated with long delays in IRB approval and identify potential strategies to streamline the review process. In collaboration with the human subjects research protection program at a large academic health center in the northeastern United States, we conducted a content analysis of minutes of convened IRB meetings for every new protocol (initial submission) approved between January and September 2019 that required greater than or equal to two full board reviews prior to approval (n = 33). We also examined characteristics of new protocols that were reviewed less than twice at convened meetings during the same time frame (n = 244). Using χ2 or Fisher's exact tests, the characteristics of protocols with multiple reviews by the convened IRBs were compared with those protocol submissions reviewed by the convened IRBs only once. Three factors significantly associated with increased delays were researcher conflict of interest (30% vs. 12%, respectively, p < .01), need for radiation safety evaluation (36% vs. 20%, respectively, p = .03), and protocols that were clinical trials (73% vs. 60%, respectively, p < .01). Other factors associated with delayed IRB approval were excessive technical jargon (93.94%, n = 31), inadequate description of data security or inability to meet data security requirements of the institution (75.76%, n = 25), protocol design affecting patient safety (57.58%, n = 19), and lack of clarity regarding compensation and payment or study duration (n = 18, 54.54% each). Approaches to mitigate delays in approval and increase the efficiency and efficacy of the IRB process are recommended.

Reducing Events of Noncompliance in Neurology Human Subjects Research: the Effect of Human Subjects Research Protection Training and Site Initiation Visits.

In an effort to minimize protocol noncompliance in neurological research studies that can potentially compromise patient safety, delay completion of the study, and result in premature termination and added costs, we determined the effect of investigator trainings and site initiation visits (SIVs) on the occurrence of noncompliance events. Results of protocol audits conducted at the National Institute of Neurological Disorders and Stroke from 2003 to 2019 on 97 research protocols were retrospectively analyzed. Based on the depth of auditing and provision of investigator research training, audit data were separated into four arms: 1) Early Period, 2003 to 2012; 2) Middle Period, 2013 to 2016; and Late Period, 2017 to 2019, further divided into 3) Late Period without SIVs; and 4) Late Period with SIVs. Events of noncompliance were classified by the type of protocol deviation, the category, and the cause. In total, 952 events occurred across 1080 participants. Protocols audited during the Middle Period, compared to the Early Period, showed a decrease in the percentage of protocols with at least 1 noncompliance event. Protocols with SIVs had a further decrease in major, minor, procedural, eligibility, and policy events. Additionally, protocols audited during the Early Period had on average 0.46 major deviations per participant, compared to 0.26 events in protocols audited during the Middle Period, and 0.08 events in protocols audited during the Late Period with SIVs. Protocol deviations and noncompliance events in neurological clinical trials can be reduced by targeted investigator trainings and SIVs. These measures have major impacts on the integrity, safety, and effectiveness of human subjects research in neurology.

Viral Load in Non-Surviving Liberian Ebola Virus Disease Patients Is Underestimated by Diagnostic qRT-PCR: A Retrospective Observational Study

Background: Viral load in Ebola virus disease (EVD) correlates with case fatality rate (CFR) and is an important parameter used for diagnostic cutoffs, stratification in randomized controlled trials, and epidemiologic investigation. However, it is currently only estimated using cycle threshold (Ct) values from diagnostic qRT-PCR tests that were not developed or validated for quantitative purposes. Furthermore, during the 2013-2016 EVD epidemic in west Africa, numerous different diagnostic platforms and protocols were used and yielded inconsistent, often conflicting data. Methods: 727 whole blood samples, both positive and negative for Ebola virus (EBOV), that were collected for diagnostic purposes in Monrovia, Liberia between August 28 and December 18, 2014 were reanalyzed under highly controlled biosafety level 4 laboratory conditions. An optimized TRIzol-based extraction protocol was utilized, followed by a novel semi-strand specific two-step droplet digital PCR assay to quantify viral load as log10 EBOV RNA copies/mL. These data were then compared to the cycle threshold (Ct) values from the original diagnostic qRT-PCR testing, and a subset of the samples was also reanalyzed following re-extraction with the same diagnostic one-step PCR and instruments employed at the Ebola treatment unit for further assessment. Finally, for EBOV-positive patients, correlations between viral load, outcome, time from symptom onset, and other epidemiological parameters were evaluated utilizing a deidentified database. Findings: Survivors had significantly lower mean viral loads at presentation than non-survivors in both the reanalyzed dataset (5.61 [95% CI 5.34 to 5.87] versus 7.19 [95% CI 6.99 to 7.38] log10 EBOV RNA copies/mL, respectively; p < 0.0001) and diagnostic dataset (Ctvalue 28.72 [95% CI 27.97 to 29.47] versus 26.26 [95% CI 25.72 to 26.81], respectively; p < 0.0001). However, receiver operating characteristic curve analysis demonstrated the reanalyzed dataset to be superior to the diagnostic dataset (area under curve 0.80 [95% CI 0.75 to 0.85] versus 0.66 [95% CI 0.59 to 0.72], respectively) in distinguishing between survivors and non-survivors and the prognostic capacity of viral load increased substantially upon reanalysis (odds ratio [OR] of death 8.06, 95% CI 4.81 to 13.53, p < 0.0001 for viral loads above 6.71 log10 EBOV RNA copies/mL versus OR of death 2.02, 95% CI 1.27 to 3.20, p = 0.0028 for Ct values below 27.37). Diagnostic Ct values underestimated viral load in non-survivors by nearly 100-fold on average (mean difference between diagnostic Ct value and reanalyzed Ct value of 5.15 [95% CI 4.43 to 5.87]); substantially less discrepancy was observed for survivors (mean difference between diagnostic Ct value and reanalyzed Ct value of 1.79 [95% CI 1.16 to 2.43]). Six samples that were reported negative by diagnostic testing were found to be positive upon reanalysis, and had high viral loads. Non-survivors presented to the ETU significantly earlier as the epidemic progressed, from 6.8 days following symptom onset (95% CI 5.7 to 7.9), on average, during the first three weeks to 3.7 days (95% CI 2.4 to 5.0) during the last three weeks (p = 0.0006) and had significantly lower viral loads (7.6 log10 EBOV RNA copies/mL [95% CI 7.3 to 7.9] to 6.5 log10 EBOV RNA copies/mL [95% CI 5.8 to 7.2] for the same intervals (p = 0.0046). However, the CFR remained steady at approximately 60% throughout. Interpretation: Inaccurate viral load estimation from diagnostic Ct values is likely multifactorial, but unaddressed PCR inhibition from tissue damage in patients with fulminant EVD may largely account for the discrepancies between the datasets in this study. In light of these findings, testing protocols for EVD require further standardization and validation to produce accurate viral load estimates, minimize false negatives, and allow for reliable epidemiological investigation. Funding Information: This research was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The deidentified samples and data utilized for this study received a determination of ‘not human subjects research’ by the NIH Office of Human Subjects Research Protection and has been approved by the University of Liberia-Pacific Institute for Research and Evaluation IRB.

IRB Reform in North America: Challenges and Opportunities

Clinical research is necessary to advance medical knowledge and to test new drugs or devices. It is therefore vital to society, and ethically imperative, that clinical studies be performed if patients are to have access to safe and effective treatments. However, clinical research by its very nature involves risk. Subjects who volunteer in clinical studies may receive no benefit; in fact, they may be seriously harmed or even die as a result of their participation. Indeed, research-related injuries and deaths, though relatively few in number (1), have become the subject of much controversy in recent years (2). Thus, the protection of human research subjects must be given the highest priority by researchers, their institutions, and the government and regulatory bodies charged with overseeing the clinical research process. Central to this process is the institutional review board (IRB) in the United States (U.S.), or research ethics board as it is known in Canada. (For the purpose of this paper, the term "IRB" will be used to refer to both American and Canadian boards.) The IRB has frequently been referred to as the "first line of defense" in research subject protection (3), yet the specific roles and responsibilities of this board and its members are not clear (4). Defining these roles and responsibilities is more important now than ever before, for several reasons.

It's the Wild, Wild West: Lessons Learned From IRB Members' Risk Perceptions Toward Digital Research Data

Digital technology that is prevalent in people's everyday lives, including smart home devices, mobile apps and social media, increasingly lack regulations for how the user data can be collected, used or disseminated. The CSCW and the larger computing community continue to evaluate and understand the potential negative impacts of research involving digital technologies. As more research involves digital data, Institutional Review Boards (IRBs) take on the difficult task of evaluating and determining risks--likelihood of potential harms--from digital research. Learning more about IRBs' role in concretizing harm and its likelihood will help us critically examine the current approach to regulating digital research, and has implications for how researchers can reflect on their own data practices. We interviewed 22 U.S.-based IRB members and found that, for the interviewees, "being digital" added a risk. Being digital meant increasing possibilities of confidentiality breach, unintended collection of sensitive information, and unauthorized data reuse. Concurrently, interviewees found it difficult to pinpoint the direct harms that come out of those risks. The ambiguous, messy, and situated contexts of digital research data did not fit neatly into current human subjects research protection protocols. We discuss potential solutions for understanding risks and harms of digital technology and implications for the responsibilities of the CSCW and the larger computing community in conducting digital research.

IRB Policies for Obtaining Informed Consent from Non-English-Speaking People.

United States regulations for the protection of human research subjects prescribe parameters for documentation of valid informed consent, which include the stipulation that the process be in a "language understandable to the subject." While significant energy has been devoted to improving the readability of consent documents, supplemental educational tools, and nuanced measurements of individual decisional capacity, there is little guidance about how to best meet the informational needs of adults with decisional capacity who do not speak English. This article reviews the institutional review board policies from the twenty-one research centers that received the most funding from the National Institutes of Health in 2018 and compares their guidelines for obtaining informed consent from non-English speakers. Inconsistent practices suggest the need for more assertive federal direction on what parameters constitute valid consent for this population. These practices also indicate a reluctance to directly engage the ethical underpinnings of consent policies for non-English speakers.

Data Integrity in Global Clinical Trials: Discussions From Joint US Food and Drug Administration and UK Medicines and Healthcare Products Regulatory Agency Good Clinical Practice Workshop.

Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording, and reporting clinical trials. Regulatory agencies conduct GCP inspections to verify the integrity of data generated in clinical trials and to assure the protection of human research subjects, in addition to ensuring that clinical trials are conducted according to the applicable regulations. The first joint GCP workshop of the US Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) and the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA-UK) was held in October 2018 and provided the agencies' perspectives on the importance of data quality management practices on data integrity. Regulatory perspectives on data blinding to minimize introduction of bias, and the role of audit trails in assessing data integrity in global clinical trials were discussed. This paper summarizes considerations of both agencies on these topics, along with case examples.

Governance of collection, use and storage of RWD in the view of data protection concerns

Abstract Issue/problem Collection, storage and sharing RWD raise concerns regarding the privacy, data protection and governance of access. To date, the concerns related to consent and adequate safeguards for data protection in conventional research and health care settings are being discussed in details in the literature. However, collection of RWD from individuals fuels questions regarding the applicability of the regulations for human subjects’ research and personal data protection. Description of the problem The data collected in the framework of RWD need to be protected in line with the overarching principles of human subjects research and personal data protection regulations such as the EU General Data Protection Regulations (GDPR). In particular, the purposes of data collection, potential further uses, duration of storage of data and the authorized users’ access to data should be managed in compliance with applicable data protection regulations. In addition, the adequate models for de-identifications of data should be used in compliance with the applicable data protection regulations. Ethical oversight on the process of data collection, storage and use should also be scrutinized. Effects/changes In order to respect the privacy rights of the patients, it is essential to first identify the potential risks and assess the adequacy of the existing safeguards in protecting the privacy of the patients. Lessons The effectiveness of the current access governance in the context of RWD should be assessed and the required safeguards to be proposed.

On creating ethical, productive, and durable research partnerships with police officers and their departments: a case study of the National Justice Database

ABSTRACTTranslational policing science must begin with explicitly communicated research aims and a shared vision for promoting safety. For researchers to approach police departments without first considering the concerns held by officers and their departments at large, is unethical, unproductive, and undermines efforts to secure longstanding mutually useful researcher-practitioner partnerships. In presenting a case study analysis of the multi-method National Justice Database’s recruitment practices, this article highlights some of the challenges that emerge when articulating study aims that hold relevance for public safety; defining theoretically- and solution-oriented research questions; administrative police data collection, analysis, and dissemination; and bolstering human research subject protection protocols for sworn officers who may be justifiably reluctant to participate in social science research endeavors. Implications for ethical policing research practice, fostering collaborative researcher-practitioner partnerships, and leveraging the benefits of data science are also discussed.

How to strengthen clinical research in Shenzhen, China: qualitative study

ObjectivesTo better understand the strengths and weaknesses, and to propose policy recommendations, regarding conducting high-quality clinical research in Shenzhen, China.DesignA qualitative study conducted from August to November 2016 using a...

A Belmont Reboot: Building a Normative Foundation for Human Research in the 21st Century.

Over the past decade, awareness emerged that existing frameworks for regulation and oversight of research with human participants fit poorly with contemporary research. Although substantial and diverse literature touches on this dissonance from a variety of perspectives, the problem is illustrated most clearly by the 2011 to 2017 process undertaken to “modernize” the Common Rule, the federal regulations for the protection of human research subjects. During this process, the Office for Human Research Protections (OHRP) sought public comment on a wide array of challenges they felt were not addressed adequately in existing regulations, and that they hoped to address in proposed revisions. The most widely debated proposal aimed to address a perception that a long-standing policy allowing the research use of nonidentified biospecimens without informed consent no longer made sense given the potential of genomic technologies to reidentify such samples.1 OHRP, recognizing concerns that existing regulations created undue burdens on very low-risk research, also proposed a plan to allow investigators to use a decision tool to determine whether a study would be “excluded” from IRB review. Proposals intended to address these and other concerns prompted critiques in the scholarly literature and in comments submitted to OHRP during the public comment period. Ultimately, the most controversial proposals, including requiring informed consent for nonidentified biospecimens research, were not part of the final rule published in January 2017 on the final day of the Obama administration. Two years after it was published, this final rule was implemented in January 2019. As leaders of a multi-disciplinary team working on the ethical and regulatory challenges raised by biorepository research in multi-site networks, we believe that both the controversy surrounding the OHRP proposals and the modest outcome of this six-year process are symptoms of a larger challenge. The regulatory revision process initiated by OHRP focused primarily on the transformation of biomedical science. Critically, however, it did not adequately consider the transformation that has occurred with regard to cultural perspectives on a range of critical issues relevant to the oversight of research with human subjects. These include, but are not limited to: changing perspectives on the right to privacy (and limits thereto), power imbalances between experts and lay people, trust in institutions, and individual ownership and control of data and biomaterials. OHRP, and the biomedical research community at large, have not resolved important questions about the oversight of human subjects research because we have not sufficiently accounted for the ways that society and societal norms have shifted since the Belmont Report was published 1979 and 45 CFR 46 Subpart A (what we now call the Common Rule) was adopted in 1981. It is time to undertake a different strategy for working toward the modernization of oversight and governance of research with humans. First, we need to revisit the principles articulated in the Belmont Report. If we aim to settle on an ethical framework that supports the development of policies, what ethical commitments and ideas must be included? Are additional ethical principles needed to ground this effort? Second, we need to conduct empirical research and public engagement activities to understand the views of diverse stakeholders on the ethical basis for policies on human subjects research. What implications do the Belmont principles hold for us today? Third, we need a process whereby this more contemporary interpretation of principles to guide human research ethics can be translated into policy and practice, with a focus that extends beyond the Common Rule to take a more comprehensive and global view of research oversight and governance. This work would recognize that changing societal contexts calls for changing approaches to process: a repeat of the original Belmont process would be an anachronism. While the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research successfully developed the original Belmont Report, it no longer makes sense for a small and distinguished group of scholars to gather at a conference center over a three-year period. Our proposal emphasizes a more transparent and inclusive – and thus more “modern” – process.

Multiple Stakeholder Views on Data Sharing in a Biobank in an Integrated Healthcare Delivery System: Implications for Biobank Governance

Background: Beginning in 2005, researchers at Kaiser Permanente Northern California (KPNC) Division of Research developed the Research Program on Genes, Environment, and Health (RPGEH), a research resource of linked biospecimens, health surveys, and electronic health records on more than 200,000 adult KPNC members. This study examined multiple stakeholders’ values and preferences regarding protection of participants’ privacy and wide sharing of participant data by RPGEH. Methods: We conducted 45 semi-structured interviews in person or via phone and two focus groups with seven stakeholder groups, including RPGEH participants and decliners who are KPNC members, KPNC research scientists, external scientists, leadership, Human Subjects Research Protection Program staff, and RPGEH Community Advisory Panel members. Results: Three major themes emerged related to: (1) perceived individual and social harms associated with data sharing; (2) concerns to address when governing access to RPGEH data; and (3) impact of a blurred boundary between research and clinical care in the context of biobanking. Conclusions: The study results were considered in the development of RPGEH data governance and motivated the inclusion of KPNC Community Advisory Panel members and ELSI experts on committees that evaluate data access proposals. Our findings can help inform other biobanks going through similar processes developing data sharing and access policies.

Prisoners as Living Donors: A Vulnerabilities Analysis.

Although national guidelines exist for evaluating the eligibility of potential living donors and for procuring their informed consent, no special protections or considerations exist for potential living donors who are incarcerated. Human research subject protections in the United States are codified in the Federal Regulations, 45 CFR 46, and special protections are given to prisoners. Living donor transplantation has parallels with human subject research in that both activities are performed with the primary goal of benefiting third parties. In this article, we describe what special considerations should be provided to prisoners as potential living donors using a vulnerabilities approach adapted from the human research subject protection literature.

Immortal Life of the Common Rule: Ethics, Consent, and the Future of Cancer Research.

The advent of the first immortal human cancer cell line in 1951 (HeLa) had profound implications for cancer research.1 Historically, the list of translational cancer research discoveries generated from human-derived cancer cell lines such as HeLa cannot be overstated.2-4 In addition, the future of the research enterprise undoubtedly depends on continued access to the biospecimens that generate such lines. However, it was the 2010 book, The Immortal Life of Henrietta Lacks, and its compelling story of the woman behind HeLa, that initiated an impassioned debate on the ethics and limits of research with such tissue.5 Applied laboratory scientists have a moral and ethical obligation to respect and honor the person from whom biospecimens were derived, but how that respect should be demonstrated is a matter of debate. The Common Rule, initially adopted in 1991, created an overarching guideline for federally funded human subjects research to provide oversight both in response to prior ethical transgressions and to present a unified ethical and regulatory framework for the future. But, in the ensuing years, the research landscape has dramatically changed in ways that could not be anticipated two decades past. Thus, a contemporary update to the Common Rule has been long overdue. After almost 6 years of careful analysis and vetting, along with public commentaries and spirited debate, 16 federal departments and agencies, including the US Department of Health and Human Services, published the eagerly anticipated final rule for the Federal Policy for the Protection of Human Research Subjects (Common Rule) on January 18, 2017, with a plan for implementation in 2018.6-8 The field of cancer research is currently in a watershed, further stimulated by the Cancer Moonshot and Precision Medicine Initiative. The pace of discoveries with immediate translational potential, particularly with regard to tumor biology/immunology and genomics, is frenetic. The translation of new laboratory data to applications at the bedside has never been more dynamic or fluid. Much of this research falls under the purview of the Common Rule and is accordingly dependent on and accountable to its stipulations and revisions. The goals of the Common Rule revisions include to “enhance respect and safeguards for research participants and to increase research efficiency by reducing unnecessary burdens and calibrating oversight to the level of risk.”9(p2293) However, many stakeholders were concerned that several proposed changes would hinder the research enterprise unnecessarily, particularly in the field of oncology. For example, the proposed Common Rule changes in the notice of proposed rulemaking (NPRM), which preceded the final rulemaking, included efforts to require broad consent for all research with biospecimens. Under the previous version, biospecimen informed consent was only required if identifying information accompanied the sample.6 The intent of the proposal—which considers any human tissue to be a human subject triggering informed consent protections—was to respect participant autonomy, but it raised the possibility of serious unintended consequences. A lively discussion ensued regarding how best to balance the need to protect and respect current participants who provide their tissue to advance scientific knowledge while ensuring scientists have the ability to advance science for future patients using invaluable biologic specimens.9-11 Ultimately, the final Common Rule was receptive to such criticisms (Table 1).13 Table 1. Summary of Major Changes to the Final Common Rule

Barred from better medicine? Reexamining regulatory barriers to the inclusion of prisoners in research.

In 2015, President Obama announced plans for the Precision Medicine Initiative® (PMI), an ambitious longitudinal project aimed at revolutionizing medicine. Integral to this Initiative is the recruitment of over one million Americans into a volunteer research cohort, the All of UsSM Research Program. The announcement has generated much excitement but absent is a discussion of how the All of Us Research Program—to be implemented within the context of social realities of mass incarcerations and racial disparities in criminal justice and healthcare—might excaberate health disparities. We examine how attainment of Initiative's stated goals of reflecting the diversity of the American population and including all who are interested in participating might be impeded by regulatory and administrative barriers to the involvement of participants who become incarcerated during longitudinal studies. Changes have been proposed to the federal policy for human subjects research protections, but current regulations and administrative policies—developed under a protectionist paradigm in response to scandalous research practices with confined populations—dramatically limit research involving prisoners. Our review provides rationale for the development of Initiative policies that anticipate recruitment and retention obstacles that might frustrate inclusivity and exacerbate health disparities. Furthermore, we question the effective ban on biomedical and behavioral research involving prisoners and advocate for regulatory reforms that restore participatory research rights of prisoners. Disparities in health and justice are intertwined, and without regulatory reforms to facilitate participatory research rights of prisoners and careful planning of viable and responsible recruitment, engagement, and retention strategies, Initiative could miss discovery opportunities, exacerbate health disparities, and increase levels of distrust in science.

Ethics committees and the changed clinical research environment in India in 2016: A perspective!

Introduction:Institutional and Independent Ethics Committees (ECs) have as their primary mission the protection of human research subjects. The Central Drugs Standard Control Organization has in the period 2013–2016 introduced several new regulations and amendments to existing regulations overseeing the conduct of Research in India. Several of these have direct effect on the functioning of the EC from a review, approval, and oversight mechanism.Methodology:The Ethics Council of Indian Society for Clinical Research conducted a questionnaire survey among EC members to understand the impact of these changes in their functioning. The domains surveyed included awareness about recent changes/amendments and impacts, serious adverse events (SAEs) and compensation, informed consent and audio-video recording, monitoring and auditing of research, and future working of ECs.Results:Seventy-nine percent of ECs are of the opinion that the new regulations/guidelines will add to their existing burden in the process of review and approval, providing subject protection and research oversight. Even though 68% of ECs stated that they are comfortable with SAE assessment and compensation determination, they state that there is variability in calculation of compensation amount using the formulae. An overwhelming majority (80%) of ECs stated that they were not in favor of centralized EC for providing review, approval, and oversight of clinical studies.Discussion:Ethics Committees act as local regulator for clinical trials at sites providing Human Subject protection. The survey captures the contemporary issues faced by the ECs and also raises important questions on the ease of doing research, oversight of approved research, and administrative burden on the EC.Conclusion:Recent changes in regulations have on the one hand empowered Ethics committees but brought in challenges in the way that they provide oversight and monitor research carried out at the site.