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CLINICAL TRIALS WITH RESPECT TO ETHICAL RESPONSIBILITY

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JANHAVI SHISODE
Journal IJLRA
ISSN 2582-6433
Published 2023/12/20
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CLINICAL TRIALS WITH RESPECT TO ETHICAL RESPONSIBILITY
 
AUTHORED BY - JANHAVI SHISODE
 
 
                                                                                                                                        I.            ABSTRACT
Clinical trials are an essential part of medical research and drug development, but they also raise complex ethical issues. This paper provides an overview of the ethical framework governing clinical trials, highlighting key principles such as informed consent, protection of vulnerable populations, and responsible conduct of research. The evolution of ethical guidelines is traced from the post-World War II Nuremberg Code to contemporary international standards like the Declaration of Helsinki. The paper discusses the importance of institutional review boards in ethical oversight, as well as the informed consent process. Challenges related to recruiting and protecting participants are analyzed. Monitoring of trials through data safety committees and adverse event reporting systems are explained as methods for upholding ethical standards. Case studies of controversial trials are presented to illustrate lessons learned about ethical lapses. Regulatory compliance and new technologies like gene editing pose emerging ethical questions in clinical research. Debates around topics like placebo controls, commercialization, and cross-cultural variations in ethics are highlighted as ongoing controversies.
 
INTRODUCTION
A.    BACKGROUND AND SIGNIFICANCE OF CLINICAL TRIALS
Clinical trials are essential to the development of new medical treatments and therapeutic interventions.[1] Before a drug or device can be approved for use in patients, it must undergo rigorous testing in clinical trials to evaluate its safety and efficacy.[2] The origins of controlled clinical trials date back to the 1940s, when the randomised controlled trial emerged as the gold standard for testing new medicines in an objective, scientific manner.[3] Since then, clinical research methodology has become increasingly sophisticated and regulated. Clinical trials typically progress through four phases, involving studies on successively larger populations. Phase I trials assess safety on a small group of healthy volunteers, while Phase II trials evaluate efficacy and side effects on patients with the target condition. Phase III trials are expanded controlled studies involving hundreds or thousands of patients to confirm efficacy and monitor adverse reactions. Finally, Phase IV trials collect data on long-term effects after regulatory approval.[4]
 
B.     RESEARCH OBJECTIVES
The main objectives of this research are:
1.      To analyze the historical evolution of ethical principles and guidelines for clinical trials, from the post-WWII Nuremberg Code to contemporary international standards.
2.      To examine the key elements of the ethical framework governing clinical trials, including informed consent, independent review boards, participant protections, and responsible conduct of research.
3.      To explore the ethical challenges in recruiting and protecting vulnerable populations as clinical trial participants, including issues of equity, access, and inclusivity.
4.      To evaluate the systems in place for monitoring trials and reporting adverse events or ethical breaches, such as data monitoring committees.
 
C.    SCOPE AND DELIMITATIONS
This research focuses on examining the ethical framework, principles, and practices governing clinical trials involving human participants. The scope includes analysis of international ethical guidelines and regulations, informed consent protocols, protections for vulnerable populations, systems for ethical oversight and reporting, as well as case studies and controversies related to clinical research ethics. The scope is limited to clinical trials for medical interventions such as drugs, devices, and biologics. The research does not extensively cover other types of human subjects research such as epidemiological studies, social science research, or psychological experiments. However, ethical issues and principles from these other research areas may be discussed to provide context and background. The paper focuses primarily on clinical research ethics from a Western perspective, drawing most examples from the United States, Canada, and Western Europe where much literature and precedent originates. However, ethical variations between Western and non-Western cultural contexts are acknowledged and addressed where relevant.
 
UNDERSTANDING CLINICAL TRIALS
A.    DEFINITION AND PHASES OF CLINICAL TRIALS
Clinical trials are research studies conducted in human volunteers to evaluate the safety and efficacy of new medical interventions, primarily drugs, vaccines, diagnostic techniques, devices, and treatment regimens. They are a key step in the drug development process before marketing approval and clinical use. The World Health Organization defines a clinical trial as "any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes".[5]
 
Clinical trials typically proceed through four phases:
Phase I trials assess safety and dosage in a small group of healthy volunteers, usually 20-100 people. Phase II expands the study to include 50-300 participants with the target medical condition to assess efficacy and side effects. Phase III trials involve large, controlled studies of 300-3000 patients to confirm effectiveness, monitor adverse reactions, compare to existing treatments, and collect data for safety reviews. Finally, Phase IV trials are conducted after marketing approval to study long-term effects and collect more safety information. Stringent ethical and scientific standards must be followed at every phase of trials to protect participants and ensure valid, useful results.[6] Failure to adhere to ethical guidelines at any stage compromises human rights and scientific integrity. Thus, understanding the staged process of clinical testing is key background for examining associated ethical requirements and challenges.
 
B.     IMPORTANCE OF CLINICAL TRIALS IN MEDICAL RESEARCH
Well-designed and ethically conducted clinical trials are essential to develop new treatments, improve medical knowledge, and provide optimal care to patients. Clinical trials enable scientists to systematically study the safety and efficacy of medications, devices, diagnostic techniques, and other interventions in human subjects before they are approved for clinical use.[7] Randomized controlled trials in particular are considered the gold standard for clinical research because they limit bias by using control groups and random assignment of participants.[8] Findings from rigorous clinical trials provide the evidence base for practice guidelines and healthcare policies. Treatments must demonstrate safety and efficacy in clinical trials before being approved by regulatory bodies like the U.S. Food and Drug Administration or Central Drugs Standard Control Organisation in India. In addition to testing new inventions, clinical trials are important to improve existing interventions, compare different treatments, gain knowledge about diseases and medical conditions, identify risk factors, and evaluate diagnostic tools.[9] They advance understanding of human biology and treatment response in diverse populations. Global collaboration in multi-site clinical trials is key to developing new therapies and generalizable medical knowledge.
 
C.    PARTICIPANTS AND STAKEHOLDERS IN CLINICAL TRIALS
The success of clinical trials depends on ethical recruitment and protection of participant populations.[10] Participants may include healthy volunteers or patients with specific conditions being studied. Special considerations apply for vulnerable groups like children, pregnant women, prisoners, and mentally disabled patients. Populations that disproportionately shoulder research burdens or receive fewer benefits raise justice concerns.[11]
 
In addition to trial participants, key stakeholders in clinical research include:[12]
·         Investigators who design and conduct studies. They have a duty to protect participants and ensure ethical practices.
·         Research institutions that oversee investigators and trials, supported by ethics review committees.
·         Sponsors, often pharmaceutical companies, who fund trials and may profit from results. Conflicts of interest must be managed.
·         Clinicians who provide medical care during trials as per protocol. They retain duties to patients as physicians first.
·         Regulators who set policies and review trial results for product approvals. They monitor ethical compliance.
·         Publishers who disseminate trial findings must consider transparency and objectivity.
 
D.    ETHICAL FOUNDATIONS OF CLINICAL RESEARCH
Modern research ethics trace back to the Nuremberg Code developed after World War II in response to gruesome medical experiments performed on concentration camp prisoners. This first international code emphasized principles like informed consent and avoiding unnecessary harm that remain pillars of clinical research ethics today. The Declaration of Helsinki further outlined ethical principles focused on medical research with human subjects.
 
·         Core ethical foundations for human subject protections include:
o   Respect for persons – recognizing human dignity and autonomy. Requires voluntary, informed consent.
o   Beneficence – duty to maximize benefits and minimize harms from research. 
o   Justice – fair distribution of risks and benefits. Protects vulnerable groups from exploitation or discrimination.
 
·         Additional key requirements are:
o   Scientific necessity, methodological rigor, and social value of research.
o   Favorable risk-benefit ratio with harm mitigation strategies.
o   Qualified investigators and ethical review committees.
o   Transparency and independent review of research proposals.
o   Protecting vulnerable populations and avoiding undue inducement. 
o   Privacy and confidentiality protections.
o   Ongoing, rigorous monitoring and reporting of adverse events.
o   Accountability for research integrity across all stakeholders.
 
ETHICAL FRAMEWORK FOR CLINICAL TRIALS
A.    HISTORICAL EVOLUTION OF ETHICAL GUIDELINES
The ethical framework governing clinical research has evolved extensively since the mid-20th century, shaped by past research abuses and increasing recognition of human rights.[13] Key historical events and guidelines include:
·         1947: The Nuremberg Code was developed following trials of Nazi doctors who conducted horrific experiments on concentration camp prisoners during WWII. It established 10 principles for ethical research like informed consent and avoiding unnecessary harm.
·         1964: The Declaration of Helsinki by the World Medical Association established core ethical principles for medical research with human subjects. It has undergone multiple expansions to add details on issues like informed consent, vulnerable populations, and research registration.
·         1966: Henry Beecher's article on "Ethics and Clinical Research" in the New England Journal of Medicine exposed unethical practices in 22 major studies, catalyzing reforms.[14]
·         Report by the U.S. National Commission outlined basic ethical principles respect for persons, beneficence, and justice that remain touchstones.
·         1981: The International Council for Harmonisation (ICH) was formed to standardize medical research guidelines across Europe, Japan, and the United States. Its Good Clinical Practice guidelines are a global standard.
·         1993: The Council for International Organizations of Medical Sciences (CIOMS) in collaboration with WHO published international ethical guidelines for biomedical research. An updated 2016 version addresses issues like standard of care, conflict of interest, and transitional trials.
·         2000s: Global clinical trial regulations like the ICH Good Clinical Practice guideline, U.S. Common Rule, and EU Clinical Trial Directive increased protections and oversight.[15]
·         2013: The Declaration of Helsinki was updated to cover issues like post-trial access, ethics review committees, and informed consent provisions.
 
B.     DECLARATION OF HELSINKI
The Declaration of Helsinki issued by the World Medical Association (WMA) is a foundational document outlining ethical principles for medical research with human subjects.[16] First adopted in 1964, it has undergone multiple expansions to remain relevant to evolving research practices and technologies.[17] The Declaration delineates responsibilities and ethical requirements for investigators, institutions, sponsors, publishers, and regulatory bodies to protect research participants.
 
Key principles include:
·         Research protocols must be submitted for independent ethics review and ongoing monitoring.
·         Participation must be voluntary with informed consent. Special protections are needed for vulnerable groups.
·         Research should be justified scientifically and build on animal studies and knowledge from other sources.
·         Risks must be minimized and reasonable compared to potential benefits.
·         Participants' privacy and confidentiality should be protected.
·         Special sensitivity is needed for research combined with medical care.
·         Negative and inconclusive results should be published to prevent redundancy and advance knowledge.
·         Any interests or incentives that could undermine scientific integrity must be disclosed.
 
The 2013 version also addresses controversies around placebo use, providing post-trial access to interventions, and standard of care for control groups. While the Declaration of Helsinki is not legally binding, it has shaped national regulations and global norms around responsible conduct of clinical research.
 
C.    ROLE OF INSTITUTIONAL REVIEW BOARDS (IRBS)
Institutional Review Boards (IRBs), also called Research Ethics Committees or Ethics Review Boards, are independent committees tasked with reviewing research proposals involving human participants to ensure ethical standards are met.[18] IRBs aim to protect the rights and welfare of research subjects by scrutinizing the scientific and ethical validity of studies before approval.[19]
 
Specific IRB responsibilities include:
1.      Assessing research risks and potential benefits to determine whether protocols adhere to ethical principles and regulatory requirements.
2.      Evaluating recruitment materials, consent processes, and procedures to protect participant autonomy.
3.      Ensuring provisions are made to protect vulnerable subjects and promote equitable selection.
4.      Requiring modifications to protocols that do not meet ethical standards.
5.      Conducting ongoing reviews of approved research and adverse event reports.
6.      Maintaining authority to terminate unethical studies.
7.      Providing participant advocates who can voice concerns.
 
INFORMED CONSENT
Obtaining voluntary, informed consent from all human participants is a fundamental ethical requirement and legal obligation in clinical research.[20] Through informed consent, investigators respect participant autonomy, ensure comprehension of material risks and benefits, and allow an individual to make a rational decision about enrolment.[21]
 
Key elements of informed consent typically include:
·         Disclosing that the study involves research and explaining purposes, procedures, and duration.
·         Describing reasonably foreseeable risks, expected benefits to participant/others, and alternatives available.
·         Ensuring comprehension by allowing questions, assessing understanding, and adapting explanations to varied populations.
·         Emphasizing voluntary participation, freedom to withdraw without penalty, and right to have interests safeguarded.
·         Protecting privacy, confidentiality, and uses of biological materials.
·         Disclosing potential conflicts of interest, sponsors, and institutional affiliations.
·         Explaining compensation and costs to determine undue inducement.
·         Providing contact information for questions and to report research-related injuries.
 
ETHICAL CONSIDERATIONS IN PARTICIPANT RECRUITMENT
Recruiting and enrolling appropriate participants is essential for clinical trial success, but raises complex ethical challenges.[22] Researchers must promote equitable selection and access while protecting vulnerable groups from exploitation or undue influence.
 
·         Target Populations and Vulnerable Groups
Clinical trials should enroll representative populations likely to use the intervention if proven safe and effective.[23] Excluding groups like women, minorities, or the elderly historically has compromised clinical value and fairness.
 
Special protections are needed for vulnerable participants with diminished autonomy like:[24]
·         Children - requires pediatric expertise and parental permissions.
·         Prisoners - high coercion risks, limited voluntary participation.
·         Pregnant women - interventions may impact fetuses, complex risk/benefit calculus.
·         Economically or socially disadvantaged - increased exploitation likelihood.
·         Terminally ill - balancing desperation and unrealistic expectations.  
·         Mentally disabled or ill - issues assessing capacity for consent.
 
Researchers should justify the inclusion or exclusion of vulnerable groups, show equitable selection, and implement added safeguards to avoid exploitation.
·         Equity and Access
Over-recruitment of certain populations due to ease of access and under-recruitment of others raises justice concerns. Researchers should ensure inclusion criteria do not intentionally or unintentionally exclude groups by gender, race, social status, or other factors irrelevant to the scientific objectives. Providing transportation, childcare, flexible scheduling, translated materials, and other accommodations can improve participation of disadvantaged groups. Community consultation and culturally adapted consent processes also promote equity.[25] 
 
·         Ethical Challenges in Recruitment
Ethical recruiting requires minimizing therapeutic misconception, undue influence, and unrealistic expectations. Using health providers as recruiters warrants caution to avoid perceived coercion. Social, professional, or financial conflicts of interest among gatekeepers, recruiters, or researchers should be disclosed. Protocols must outline ethical strategies for identifying and enrolling qualified participants. IRBs scrutinize recruitment materials and plans to ensure protections against undue influence and promote diversity.
 
MONITORING AND REPORTING ETHICAL ISSUES
Stringent monitoring and reporting mechanisms are crucial to ensure adherence to ethical protocols and identify issues arising during clinical trials.[26] Key oversight processes include data monitoring committees, adverse event reporting systems, and protections for whistleblowers.
 
·         Data Monitoring Committees 
Data monitoring committees (DMCs) are independent expert panels that regularly review accumulated trial data for participant safety and study integrity.[27] DMCs look for efficacy signals to halt futile trials, or clear harms to stop dangerous experiments. They advise sponsors on continuing, modifying, or terminating studies. DMCs provide ongoing rather than one-time ethics review, assessing adverse reactions, protocol deviations, recruitment biases, safety considerations for vulnerable subjects, and other issues threatening scientific validity or indicating potential harm. Strict confidentiality protects impartiality and trial integrity.
 
·         Adverse Event Reporting 
Detailed adverse event reporting allows close tracking of harms to participants, enabling corrective actions in ongoing trials and informing future research. Timely, accurate reporting also upholds transparency and public trust. Sponsors must submit expedited reports of serious, unexpected adverse reactions to regulators. Investigators report adverse events through IRBs and sponsors. Study protocols should delineate reporting procedures and responsible parties to catch issues early.[28]
 
·         Whistleblowing Protections
Effective whistleblower policies enable detection of unreported abuse, misconduct, protocol violations, undisclosed risks, and other ethical breaches. But researchers who voice concerns often face retaliation, especially when revealing issues that threaten profit or professional success. Robust protections are needed against firing, lawsuits, blacklisting, loss of funding or reputation, and other reprisals faced by whistleblowers.[29] Anonymity safeguards, anti-gag rules, and prohibitions on retaliation can encourage speaking out to uphold ethics.  Responsible oversight requires ongoing vigilance and multiple safe reporting channels to protect human subjects from foreseeable and unexpected harms in clinical trials.
 
CASE STUDIES IN ETHICAL RESPONSIBILITY
Examining controversial past trials provides important lessons for research ethics and oversight.[30] Two major cases involving serious lapses are the Tuskegee Syphilis Study and the surfactant trials by Columbia University:
 
·         Tuskegee Syphilis Study[31]
This notorious U.S. Public Health Service study recruited 600 poor, African American men beginning in 1932. Researchers aimed to observe untreated syphilis, even after penicillin became an effective cure in 1947. Key ethical failings included:
·         Deception about study purposes - participants were misinformed the study was to "treat bad blood." No disclosure of withholding treatments was given.
·         No informed consent - participants were not informed they had syphilis or given information on its progression.
·         Targeting vulnerable populations - recruitment focused on poor, disadvantaged minorities with limited healthcare access.
·         Failure to provide available treatments - penicillin was withheld long after validated as effective therapy.
 
·         Lack of ethics review - no oversight or independent evaluation of ethics.
The study continued until public exposure in 1972, leading to reforms in ethics regulations like required ethics board review and informed consent. Its legacy remains as a notorious example of exploitation and lack of human subject protections.
 
·         Surfactant Trials, Columbia University[32]
In the 1990s, trials by Columbia University researchers tested a synthetic surfactant to treat respiratory distress in premature infants. Major ethical concerns emerged:
·         Inadequate informed consent - consent forms lacked information on risks, purpose was obscured as "breathing study", and translations were non-existent for non-English speaking parents.
·         Undue inducements - recruitment offered free medical care to uninsured women and families.
·         Unclear risk-benefit profile - animal studies suggested potential brain damage risk to infants, but protocols continued without established benefit.
·         Failure to disclose conflicts - the trial sponsor stood to profit from approving the costly surfactant.
·         Targeting vulnerable populations - mothers were recruited from underserved New York communities without full comprehension or choices.
·         Lack of ethics review - an inadequate IRB review process approved the flawed studies.
The trials resulted in over $700,000 in fines, jailing of the lead researcher, and banning of the paediatric hospital from trials. The case illustrated glaring oversights in protecting vulnerable participants and informed consent.
 
ETHICAL RESPONSIBILITY IN EMERGING TECHNOLOGIES
Emerging technologies like artificial intelligence, gene editing, and autonomous vehicles are rapidly developing and being deployed in society. However, they also raise complex ethical issues that companies, regulators, and society must grapple with. Some key ethical responsibilities around emerging technologies include:
·         Ensuring transparency and explainability: Many advanced systems like deep learning AI are complex "black boxes" that are not easily understandable by average users. There is an ethical imperative for companies deploying such systems to ensure there is transparency around how they operate and make decisions, so that biases can be detected and users have agency.[33]
·         Protecting privacy and consent: The collection of data is core to many innovations, but there is a duty to gather and use data ethically and respect individual privacy. Obtaining informed consent from users, anonymizing data, and providing strong cybersecurity are important safeguards.[34]
·         Considering bias and fairness: Much research shows that datasets and algorithms can perpetuate or amplify existing societal biases around race, gender, etc. Companies must proactively assess and mitigate these risks through techniques like rigorous testing for disparate impact.[35]
·         Anticipating consequences and misuse: Emerging technologies require examining not just intended applications but also potential misuse, such as weaponization of AI. Scientists and engineers have a moral duty to carefully consider long-term effects before releasing powerful technologies.[36]
·         Aligning with human values and ethics: For advanced systems like care robots or autonomous cars, philosophical perspectives on ethics should inform their behavior and decision architectures. Ensuring human values are respected is crucial.
 
CHALLENGES AND CONTROVERSIES
Clinical trials involve inherent ethical tensions between generating generalizable knowledge to improve human health and safeguarding the rights and wellbeing of individual participants. Key controversies include:
·         Informed consent - Ensuring truly voluntary and informed consent from participants with varying backgrounds and literacy presents challenges. Controversies exist around appropriate compensation, understanding of risks, and coercion.
·         Standard of care - Debate persists on whether trial participants from poor backgrounds should receive the global best standard of care or local standard, which may be much lower. The injustice of lower standards must be balanced with feasibility and social value.
·         Placebo controls - Using placebos rather than proven treatments as controls raises ethical concerns, though may be acceptable if no proven alternative exists and risks are minimized. Strict guidelines are required to avoid exploiting vulnerable populations.
·         Vulnerable populations - Special protections are required when recruiting marginalized groups like tribal communities, but over-protection risks limiting their access to potential benefits of trials. Balancing protections and inclusion is complex. 
·         Post-trial access - Sponsors may have limited ability to provide successful drugs long-term after trials end. But failing to ensure access to beneficial treatments raises injustice concerns. Creative solutions like licensing deals with local companies are needed.
·         Conflicts of interest - Financial interests of sponsors, researchers, and ethics committees may consciously or unconsciously bias trial conduct and reporting. Strict disclosure norms and protocols are essential.
·         Data transparency - Selective publishing of positive results and withholding negative findings biases the evidence base. Mandating registering and reporting all trial results, including failed trials, improves transparency.
·         Regulatory gaps - Regulations often fail to keep up with emerging technologies and techniques like online recruiting, virtual informed consent, and tele-trials. Updating rules and training ethics committee members is important.
 
CONCLUSION
Clinical trial research is essential to develop new treatments and advance medical knowledge, but also raises complex ethical challenges. As trials involve intervening on human subjects, protecting participants and ensuring responsible conduct are imperative. India has seen rapid growth in clinical trials, accentuating the need for robust ethics oversight and legal frameworks aligned with global norms. India's ethical guidelines and regulations largely model international standards, with ethical principles like autonomy, beneficence, non-maleficence and justice underpinning informed consent requirements, independent ethics reviews, participant protections, and transparency mandates. For example, the ICMR National Ethical Guidelines builds on the Declaration of Helsinki, while Schedule Y of the Drugs and Cosmetics Rules mirrors ICH-GCP guidelines. Regulatory gaps remain, but the Drugs and Cosmetics (Amendment) Act 2021, clinical trial rules 2019, and other reforms have strengthened oversight.
 
Despite this convergence, India's socio-economic context poses distinct ethics challenges. Low literacy, health awareness and access create barriers to meaningful informed consent. The Belmont Report's principles apply universally, but translating them into practice requires local adaptation. Initiatives like audio-visual aids, community consultation, and translations help bridge gaps in comprehension and voluntariness. But continuous ethics education of investigators and participants is vital. Providing quality universal healthcare remains an aspiration in India. Against this backdrop, debates persist on appropriate standards of care for trial subjects versus the broader patient population. While pragmatic trials within local resource constraints have value, exploiting vulnerabilities would be unethical. Ethics committees must review care standards on a study-by-study basis, guiding sponsors to uphold moral obligations.
 
With overlapping social disadvantages, ethical recruitment of marginalized communities like tribes requires special protections without limiting access to potential benefits of research participation. Law mandates specific approval processes for tribal trial sites, aiming to balance vulnerability and inclusion. But meaningful implementation hinges on ethics review capacity, investigators' conduct, and community engagement. Open dissemination of trial findings is critical from ethics and public health perspectives. India mandates registering trials and disclosing results to address selective publishing. But compliance remains inconsistent, undermining evidence-based policy. Strict penalties for non-disclosure and platforms like CTRI that facilitate access to aggregated trial data can improve transparency.
 
Looking ahead, India must continue updating regulations to align with emerging science, while strengthening ethics review and enforcement capacities. But law can only provide an enabling framework. Ensuring ethical values guide all trial conduct ultimately relies on investigators, sponsors and institutions internalizing those values. Alongside mandatory compliance, promoting ethics education and a culture of integrity across the research enterprise is imperative. With its vast patient pool, genotypic diversity, infrastructure and cost advantages, India's strategic importance in global clinical research will only grow. Realizing the full potential of ethical trials that uphold participant protections while fostering R&D and medical progress requires continued dialogue. Engaging with diverse stakeholders - regulators, ethics committees, investigators, participants, sponsors, media and civil society - builds shared understanding of ethical challenges and responsibilities. Incorporating critical perspectives can refineboth regulations and voluntary best practices. As a vital link between global pharma's commercial interests and local realities, ethics committees must be strengthened to discharge their duties effectively. Guided by ethics, India's expanding clinical research ecosystem can responsibly harness opportunities for social benefit.

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Article Information

CLINICAL TRIALS WITH RESPECT TO ETHICAL RESPONSIBILITY

Authors: JANHAVI SHISODE

  • Journal IJLRA
  • ISSN 2582-6433
  • Published 2023/12/20
  • Issue 7
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