Oversight Of Clinical Research Research Articles

Vliv pandemie onemocnění covid-19 na provádění klinických hodnocení a možné etické dopady

The COVID-19 pandemic led to significant changes of the usual procedures in the clinical trials conduct, as well as to modifications of the relevant study documentation, which also affected regular quality assurance activities ensuring the safety of clinical trial participants, compliance with good clinical practice, and the integrity and validity of the clinical trial data collected during the COVID-19 pandemic. The paper deals with the ethical guidelines and legal regulations that govern the conduct of clinical trials and discusses the ethical implications that arose from the forced adjustments of routine processes and procedures in the clinical trial conduct during the COVID-19 public health emergency. The paper also reflects on the ethical consequences of conducting clinical trials during the public health emergency, as well as on means of performing quality assurance activities and a regular oversight of clinical research.

Ethical and regulatory oversight of clinical research: The role of the Institutional Review Board.

The history of clinical research is, unfortunately, filled with examples of research studies that took advantage of and harmed research participants, to fulfill the research goals of scientists. Over time, we have created a system of ethical codes, principles, and regulations that are designed to prevent these abuses and to ensure that the rights and welfare of research participants are protected and honored. This review article will provide a brief history of clinical research ethics and ethical codes, outlining how those codes developed into the current regulatory requirements for the ethical oversight of clinical research. Understanding the current human subject protection systems will allow researchers to use best practices for planning and conducting rigorous, scientifically valid and ethical clinical studies. Understanding the history, principles, and foundations of the development of this system will equip researchers to understand what resources are available to them and how to make the best decisions when confronted with unique ethical situations in the conduct of their research.

A Changing World in Gene Therapy Research: Exciting Opportunities for Medical Advancement and Biosafety Challenges.

Introduction: We previously reported on the United States' regulatory environment evolving to accommodate an emerging boom in gene therapy research. Several important developments have transpired in the 2 years since that article was published, including the coronavirus disease 2019 (COVID-19) pandemic and the drive for large-scale testing of vaccines containing recombinant or synthetic nucleic acid molecules. This report highlights key developments in the field with a focus on biosafety and issues of note to biosafety professionals with responsibilities over clinical research.Discussion: We provide guidance for performing risk assessments on the currently approved gene therapy products as well as the most utilized types of investigational products in clinical trials. Areas of focus include the prominent approaches utilized in the three major areas of research: oncology, infectious diseases, and rare diseases.Conclusion: The COVID-19 pandemic has created several opportunities for continued growth in gene therapy. National vaccination campaigns will result in greater public acceptance of gene therapy research. Technological advancements that made the vaccine race possible will spur the next generation of research. Advancements born in the developed world set the stage for the creation of therapeutics to treat greater numbers in the developing world and have the potential for massive benefits to global public health. Biosafety professionals and Institutional Biosafety Committees play key roles in contributing to the safe evidence-based advancement of gene therapy research. Biosafety professionals responsible for clinical research oversight must be aware of emerging technologies and their associated risks to support the safe and ethical conduct of research.

PO 8381 REGULATING CLINICAL TRIALS DURING AN EBOLA EMERGENCY: THE LIBERIAN EXPERIENCE

BackgroundEffective clinical trials oversight is a major function of a fully functional national medical products regulatory system. However, exercising clinical trial oversight in a resource-limited environment is challenging, in particular during an Ebola outbreak or health emergency. Until the devastating Ebola virus disease (EVD) outbreak in 2014, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) had no capacity for effective clinical trial regulation. This presentation describes the main challenges encountered by LMHRA in regulating clinical trials in Liberia during the largest EVD outbreak that affected West Africa in 2014 and 2015.MethodsBy carefully documenting activities during the EVD outbreak, interviewing key stakeholders, and discussions among the LMHRA clinical trial committee, key challenges observed during the outbreak were identified and documented.ResultsLimited financial resources, lack of expertise in clinical trials, inaccurate and insufficient information about the functions of the LMHRA, poor coordination among key stakeholders, and the lack of a well-developed regulatory framework, adversely influenced the LMHRA clinical trial oversight performance during the EVD outbreak.ConclusionIt is true that several challenges need to be addressed when regulating a clinical trial in a limited-resource environment during any disease outbreak or international medical emergency. However, the importance of building local expertise in clinical trials through mentorship and training cannot be overemphasised. By taking advantage of grants from developmental partners, national medicines regulatory authorities in resource-limited environments can develop capacity for clinical research oversight.

Bioethics in the Oversight of Clinical Research: Institutional Review Boards and Data and Safety Monitoring Boards.

This article describes oversight mechanisms for clinical research that have developed substantially over the last few decades, including institutional review boards and data safety and monitoring boards. LeRoy Walters and others in the 1970s in the US thoughtfully described the importance of fundamental ethical principles and the application of bioethics to clinical research. Dr. Walters's important essay and work with the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research helped identify and explain ethical principles that guide research. These principles, subsequently enunciated by the Commission in the Belmont Report, remain central to our understanding of the ethics of clinical research and are the foundation of our regulations. In this article, I review some history, successes, and challenges of IRBs and DSMBs to exemplify the significance of understanding and applying ethical principles to the design and conduct of clinical research, and to honor Dr. Walters's contributions.

Current status of standardized, quality and ethical oversight of clinical research in the country: An audit of the Central Drugs Standard Control Organization (registration of ethics committees) and national accreditation board for hospital and healthcare providers (accreditation) databases.

Purpose:The Prof. Ranjit Roy Chaudhury committee report recommended the accreditation of Institutional Ethics Committees (IECs). Rule 122DD of the Drugs and Cosmetics Act (and Rules) mandates that only registered ECs can accord approval for regulatory studies. We evaluated the current status of registered, reregistered, and accredited ECs in the country to assess the impact of both the recommendation and rule.Materials and Methods:Websites of stakeholders-the Central Drugs Standard Control Organization (CDSCO), National Accreditation Board for Hospitals and Healthcare Providers (NABH) were assessed. Information on registration status was then compared with regulatory clinical trials in the Clinical Trials Registry of India, population demographics of all states, and the Medical Council of India recognized postgraduate medical colleges in the various states.Results:A total of 1268 ECs were registered with CDSCO. Of these, 1008 (79.5%) were institutional and 256 (20.18%) independent ECs. A total of 499/1268 (39.4%) ECs were reregistered. Of which 449/499 (90%) were institutional and 50/499 (10%) were independent. Institutional ECs were five times more likely to be reregistered with CDSCO relative to independent ECs (cOR 4.52 [3.12, 6.54], P < 0.0001). A total of 15/233 (7%) applications to NABH had received accreditation. A wide skew was seen in the distribution of ECs across various states as also their oversight of regulatory clinical trials.Conclusions:Registration and reregistration of ECs along with accreditation is not commensurate with the needs of the country at this time and must be vigorously promoted.

Society for immunotherapy of cancer (SITC) statement on the proposed changes to the common rule

The Common Rule is a set of ethical principles that provide guidance on the management of human subjects taking part in biomedical and behavioral research in the United States. The...

Barriers to Effective Deliberation in Clinical Research Oversight.

Ethical oversight of clinical research is one of the primary means of ensuring that human subjects are protected from the natural bias of researchers and research institutions in favor of experimentation. At a minimum, effective oversight should ensure that risks are minimized and reasonable in relation to anticipated benefits, protect vulnerable subjects from potential coercion or undue influence, ensure full and informed consent, and promote the equitable distribution of the risks and benefits of research. Because these assessments often involve value judgments for which there are no agreed-upon objective standards, we rely on deliberative procedures thought to have the greatest likelihood of producing the right or best outcomes. Concerns about the potential for improperly functioning IRBs to waste scarce human and institutional resources and impede biomedical progress have motivated a surge in empirical research assessing their procedures and outcomes. Yet within this literature, there has been minimal attention paid to the social scientific evidence regarding how individuals and deliberating groups make decisions, nor how those data might inform IRB practice. This essay seeks to fill that gap, locating recent empirical data on IRB composition and process within the context of data regarding what I call "deliberative pathologies," or instances when deliberation fails to live up to one or more aspect of the deliberative ideal because of systematic biases in the ways participants interact. The paper goes on to make evidence-based recommendations to reduce the vulnerability of IRB deliberations to the kinds of pathologies discussed and indicate directions for future research.

Exploring the ethical and regulatory issues in pragmatic clinical trials.

The need for high-quality evidence to support decision making about health and health care by patients, physicians, care providers, and policy-makers is well documented. However, serious shortcomings in evidence persist. Pragmatic clinical trials that use novel techniques including emerging information and communication technologies to explore important research questions rapidly and at a fraction of the cost incurred by more "traditional" research methods promise to help close this gap. Nevertheless, while pragmatic clinical trials can bridge clinical practice and research, they may also raise difficult ethical and regulatory challenges. In this article, the authors briefly survey the current state of evidence that is available to inform clinical care and other health-related decisions and discuss the potential for pragmatic clinical trials to improve this state of affairs. They then propose a new working definition for pragmatic research that centers upon fitness for informing decisions about health and health care. Finally, they introduce a project, jointly undertaken by the National Institutes of Health Health Care Systems Research Collaboratory and the National Patient-Centered Clinical Research Network (PCORnet), which addresses 11 key aspects of current systems for regulatory and ethical oversight of clinical research that pose challenges to conducting pragmatic clinical trials. In the series of articles commissioned on this topic published in this issue of Clinical Trials, each of these aspects is addressed in a dedicated article, with a special focus on the interplay between ethical and regulatory considerations and pragmatic clinical research aimed at informing "real-world" choices about health and health care.

Perceptions and Experiences of Community Members Serving on Institutional Review Boards: A Questionnaire Based Study

The community representative plays a very important role in an institutional review board (IRB) but there is sparse data about their understanding of their role in an IRB. This study was conducted to assess perceptions of community members serving on IRBs of one region in India. A validated questionnaire (Cohen's kappa coefficient of 0.84) was administered to community members of IRBs in a prospective cross-sectional study. The questions related to demography, perceptions of their role in the IRB, experiences while serving on the IRBs, difficulties faced by them, and suggestions to improve their contributions. Of the 56 IRBs contacted, all 15 of thepublic institutions shared details of their community members, while only 26 of the41 IRBs of private institutions responded. When questioned about why they joined theIRB, one third of therespondents said either that there was "no specific reason" for joining or that they accepted the invitation to serve on the insistence of other members of the IRBs or the head of theirinstitution. All except one felt that community members were needed for optimal functioning. Six participants said that they did not review informed consent documents (ICD), and 10 were unaware that their presence was vital for quorum to be met. Twenty-eight said they participated actively in meetings and did not feel intimidated by the presence of clinicians. Twelve reported difficulties in understanding medical terminologies in ICDs. Although the majority of participants were aware about their role in an IRB, some did not review important documents such as ICDs. Restricted participation by private hospital IRBs was a striking observation in our study. There is a need to define eligibility criteria and develop targeted training modules for community members to ensure their effective contribution to effective oversight of clinical research.

Reviews in Medical Ethics

What the Doctor Didn’t Say, by Jerry Menikoff and Edward P. Richards, is a courageous and well-written volume that examines some of the fundamental debates pertaining to the ethics of clinical research. The volume deserves a careful reading by anyone with a potential role in clinical research: clinicians who might serve as investigators or refer patients to clinical trials; research staff; Institutional Review Board (IRB) members and administrators; sponsors who design clinical trials; and the book’s intended audience, namely, potential research participants and their families. A cursory reading of this volume might lead one to think that Menikoff and Richards have declared war on clinical research. They have not. Instead, they offer an in-depth study of the conduct and oversight of clinical research through the lens of law and ethics. They shed light on old issues and initiate discussion of new questions, challenging readers to think critically about the relationship between medical ethics, research ethics, the law, and the conduct of clinical research.

Reforming the Oversight of Multi-Site Clinical Research: A Review of Two Possible Solutions

The current system for the ethical oversight of clinical research suffers from structural, procedural, and performance assessment problems. Initially conceived primarily to handle local investigator-initiated single-site studies, the system of institutionally-based committee review has become progressively more inefficient given the increased prevalence of commercially or federally sponsored multi-center trials. To date, proposed solutions do not adequately address these problems. Beginning with a review of these structural, procedural, and performance assessment problems, this article will then consider two proposals for addressing these deficiencies: (a) regional ethics organizations; and (b) IRBNet™, a newly developed web-based program for cooperative IRB review. The strengths and weaknesses of these two approaches will be evaluated in light of recent experience with centralized review. The proposal to establish a system of regional ethics organizations presents a comprehensive approach to many of the problems faced by the current system. However, IRBNet™ offers an immediate and feasible solution to many of the problems faced by the review of multi-site clinical studies. IRBNet™ has been developed by Elizabeth A. Bankert, MA and Robert M. Nelson, MD, PhD through a cooperative venture of Dartmouth College and The Children’s Hospital of Philadelphia, funded by the National Institutes of Health through a Human Subjects Research Enhancement Award (1 S07 RR18181). IRBNet™ has subsequently been transferred to a private entity for commercial development.

Quality assurance for clinical research: challenges in implementing research governance in UK hospitals.

The oversight of clinical research in the UK is currently in a state of flux. Discusses the quality assurance problems that have arisen in the management of research and the protection of the rights of human participants. Contrasts clinical governance and regulatory approaches to research quality assurance and performs a critical analysis of the Department of Health (England) Research Governance Framework (RGF) to see where it falls within the continuum. Highlights the implications for UK hospitals engaged in clinical research through the presentation of a case study in implementing the RGF. Concludes by suggesting the priority areas that need to be addressed and invites further debate regarding the merits of a clinical governance or regulatory approach to research quality assurance.

American Society of Clinical Oncology policy statement: oversight of clinical research.

American Society of Clinical Oncology policy statement: oversight of clinical research.

Toward protecting the safety of participants in clinical trials

It is a widely held belief that the current system of oversight of clinical research, particularly the means of assessing risks and minimizing harms to participants in clinical trials, could be improved. In particular, the system is inefficient with overemphasis on the monitoring ability of some groups such as research ethics review boards and investigators, underemphasis on others such as data monitoring committees (DMCs) and sponsors, confusion about responsibilities for safety and imperfect communication between these different groups. Research ethics review boards are not able to perform safety monitoring by review of individual adverse events and are often burdened by duplicative reviews of large multicenter studies. There are no standards for DMCs to ensure they can reliably identify safety issues. Sponsors may be overreliant on data audits and slow to disseminate safety data in a coherent summary. Investigators, their staffs and clinical sites may not fully appreciate all the nuances of good clinical practice or may be inattentive to the daily conduct of studies. Regulators, particularly those in the United States, have failed to completely harmonize their policies with each other or with international regulatory agencies. We recommend well-designed monitoring plans for all studies that are appropriate to their scope and risk, more centralized review of large multisite studies and closer local scrutiny of single-institution studies. In addition, sponsors should pay greater attention to monitoring adverse events and keeping up-to-date databases or investigator's brochures emphasizing safety issues. A minimal standard of education or expertise in good clinical practice should be established for investigators, their staffs and research ethics review board members. DMC composition and functions should be standardized and regulations should be harmonized nationally and internationally. Finally, there should be a concerted effort to study the efficacy of various components of the system.

Academic-industrial relationships: opportunities and pitfalls.

Over the past 50 years, academic-industrial collaborations and technology transfer have played an increasingly prominent role in the biomedical sciences. These relationships can speed the delivery of innovative drugs and medical technologies to clinical practice, creating important public health benefits as well as income for universities and their faculty. At the same time, they raise ethical concerns, particularly when research involves human subjects in clinical trials. Lapses in oversight of industry sponsored clinical trials at universities, and especially patient deaths in a number of trials, have brought these issues into the public spotlight and have led the federal government to intensify its oversight of clinical research. The leadership of Harvard Medical School convened a group of leaders in academic medicine to formulate guidelines on individual financial conflicts of interest. They and other groups are working to formulate a national consensus on this issue.

Prematurity in gene therapy.

Prematurity in gene therapy.

Bioethics Panel Urges Broader Oversight

HUMAN EXPERIMENTATIONThe U.S. government should create a single office to monitor both public and private research involving human volunteers, says a new report by a presidential commission. The report, 5 years in the making, concludes that major changes are needed in the oversight of clinical research. But it's not clear if the new occupant of the White House is listening.

Is Clinical Research Oversight Adequate in the United States?

Is Clinical Research Oversight Adequate in the United States?

Oversight mechanisms for clinical research.

Clinical research provides a critical mechanism for the transformation of health care into a cost-effective and evidence-based system. Oversight of clinical research will require development of coherent means of protecting the rights of human subjects without unduly adding bureaucratic hurdles and costs that can hinder the protection intended.