Regulatory Committees Research Articles

Towards inclusion: a comparative examination of the status of disability acts in South Asia

ABSTRACT This article compares the recent disability legislation in India, Nepal, Bangladesh, and Maldives after signing the CRPD in 2006. Through a systematic comparative approach, this study identifies and examines the commonalities and differences in the provisions, participation of persons with disabilities (PWD), educational considerations, and rights of women with disabilities within their disability Acts. Qualitative content analysis has been used for thematic analysis of the content of these legal documents. The analysis revealed that a shared philosophical assumption existed across the Acts influenced by the social model of disability, while variations exist in the definition of disabilities across these Acts. It was found that due emphasis was placed on the involvement of PWD in regulatory committees in all Acts taken in the study. However, the level and extent of participation in these committees vary among countries. The nature of the educational provision is more inclined towards inclusive education across these Acts. However, not all of these four practices fully include PWD. Less emphasis has been put on including the rights of women with disabilities in the Acts. This article accentuates the importance of comparative studies for cross-country learning and the potential for adapting ideas to suit respective countries' national contexts.

Swallowed topical steroid therapy for eosinophilic oesophagitis in children: practical, evidence-based guidance by the BSPGHAN Eosinophilic Oesophagitis Working Group

ObjectiveTo develop evidence-based guidance for topical steroid use in paediatric eosinophilic oesophagitis (pEoE) in the UK for both induction and maintenance treatment.MethodsA systematic literature review using Cochrane guidance was carried...

Exercise oncology clinical trials during treatments: a commentary to address the safety concerns of human subjects regulatory reviewers and committees.

Exercise oncology clinical trials contribute to the advancement of our scientific knowledge and to the safety and care of patients diagnosed with cancer. Nevertheless, regulatory reviewers and committees may not be familiar with the well-documented long-term health benefits and safety of the regular practice of physical activity. Moreover, they may not see how the benefits outweigh the risks in the context where patients diagnosed with cancer are typically seen as vulnerable. Therefore, we would like to provide a purpose-built overview of exercise oncology clinical trials for members involved in institutional review committees, including the Scientific Review Committee (SRC), the Institutional Review Board (IRB), and the Data Safety Monitoring Committee (DSMC) to facilitate a greater understanding of the safety and benefits of physical activity during cancer treatments. Communication is key to improve the success of exercise oncology clinical trials, which are vital for patients diagnosed with cancer.

Stochastic evolutionary game analysis of food cooperation among countries along the Belt and Road from the perspective of food security

IntroductionIn recent years, the combination of the public health crisis and the climate crisis has greatly weakened the resilience of food systems. The Belt and Road food cooperation will make outstanding contributions to consolidate food security and reduce global poverty in countries along the Belt and Road.MethodsThis paper constructs a three-party stochastic evolutionary game model from the perspective of food security, distinguishes the difference between large and small countries by calculating the cereal self-sufficiency rate, which studies the cooperation strategy with the Belt and Road cereal large countries, cereal small countries and regulatory committees as the object. In addition, we introduce the Gaussian white noise characteristics to characterize the stochastic disturbance of the game system. Then we combine the mathematical derivation of the stochastic evolutionary game analysis with the simulation method, examine the effect of the stochastic disturbance factors on the cooperation, and find out the factors that affect the cooperation. And finally verifies the model and proves the reasonableness and practicability of the model.ResultsThe stochastic evolutionary game model analyzes the interaction of stochastic disturbance and influencing factors from a dynamic perspective, and the stability of evolution is related to the strength of Gaussian white noise. The level of effort of large cereal countries and the incentives of regulatory committees can have a positive impact, but high income in small cereal countries can lead to instability in the strategic choices of other players.DiscussionTaking the countries along the Belt and Road as the research object, Gaussian white noise is introduced to describe the stochastic external environment, discriminate the stability of the game system through stochastic differential equations, and analyze the influencing factors of the dynamic behavioral strategies of the parties in combination with simulation methods. To improve the capacity of national food security governance and help improve the resilience of the world food system.

Finding Your Seat at the Table: Roles for Librarians on Institutional Regulatory Boards and Committees

Finding Your Seat at the Table: Roles for Librarians on Institutional Regulatory Boards and Committees

Current status of approaches of Universities in fostering research ethics in Thailand

ABSTRACT Research ethics and integrity are essential topics that researchers should always be concerned about and are emphasized by academic communities around the world. However, there is currently little information about the mechanisms to regulate research ethics and integrity in Thailand. Therefore, the aims of this study were to determine the approaches that universities used to support research ethics and integrity in Thailand and also to identify the barriers that may obstruct the development. A questionnaire was used to explore the strategies about research ethics of 44 Thai universities. It was found that the first three mechanisms used to foster research ethics and integrity were establishment of institutional regulatory research committees (84%), conduction of research ethics training programs (77%), and policy adoption (68%). Interestingly, there was a significant association between the sizes of universities and establishment of institutional regulatory research committees. The medium and small universities might need more support to develop their own research ethics regulatory mechanisms. The results here indicated good signs for Thailand about preparing basic structures for fostering research ethics and integrity. The recognition of this current status could provide the useful information for future development of research integrity in Thailand.

Early risk assessment in paediatric and adult household contacts of confirmed tuberculosis cases by novel diagnostic tests (ERASE-TB): protocol for a prospective, non-interventional, longitudinal, multicountry cohort study

IntroductionThe WHO End-TB Strategy calls for the development of novel diagnostics to detect tuberculosis (TB) earlier and more accurately. Better diagnostics, together with tools to predict disease progression, are critical...

The Expansion of Turkey’s Medical Tourism Industry

The Expansion of Turkey’s Medical Tourism Industry

The Ethical Dilemma of Non-Human Primate Use in Biomedical Research

The Ethical Dilemma of Non-Human Primate Use in Biomedical Research

Health regulation and technological development: innovative strategies for accessing medicines in the SUS.

Regulatory science involves articulating knowledge that can establish the scientific bases for the definition of adequate and efficient regulatory mechanisms and practices. The interfaces between systemic and sectoral health and technological development policies were studied based on documentary analysis, especially from the National Pharmaceutical Policy (PNAF), with impacts on health regulation and stimulating the production of medicines of interest to the Unified Health System (SUS). The initiatives for the nationalized production of ARV "Efavirenz", which was the subject of a compulsory license in 2007, and the establishment of Partnerships for Productive Development (PDP), contributed to defining innovative regulatory frameworks and practices, emphasizing the Regulatory Technical Committees (CTR) for monitoring the internalization of technologies and health registration of the resulting products. The permeation capacity of the principles and strategic axes of the PNAF was identified in the sectoral policies that were analyzed. As of 2014, no macro or sectoral policies on expanding access to medicines in the SUS with impacts on regulations were identified.

George Kaufman: Both Hands In; Scholar’s Work with Academia and Financial Industry Benefitted Both

This paper examines the career of economist Prof. George Kaufman, whose work combined and benefited both academia and the financial industry, helping both better understand the problems of financial stability, financial regulation, and financial sector competition. In doing so, he brought together great minds from both fields and helped many economists progress in their careers. Prof. Kaufman promulgated the idea that government policy needed to foster two simple goals: proper incentives and competitive markets. He believed the combination would produce a richer society and more stable economy. He created the U.S. Federal Reserve’s Conference on Bank Structure and Competition, the leading conference in the world addressing financial regulatory issues for 50 years. Prof. Kaufman also founded the U.S. Shadow Financial Regulatory Committee in 1986 in the midst of the thrift crisis, helping to solve that crisis and inspiring the creation of other shadow financial regulatory committees around the world. Through his activities, he left behind an outstanding legacy of leadership, research, and opinion in various economic fields, providing platforms upon which many scholars will build in the coming decades.

ISEE principles for evidence synthesis and evaluation in environmental health: comments from experience on advisory and regulatory committees

BACKGROUND AND AIM: This presentation is an individual viewpoint, but draws on my experience serving on various official committees which undertake evidence synthesis, including the UK Industrial Injuries Advisory Council, the UK Committee on Carcinogenicity, and a subcommittee of the European Food Safety Association (EFSA) Scientific Committee. METHODS: It used to be a ‘given’ that to decide whether a particular factor, either exogenous or endogenous, can cause a particular disease, and in what order of magnitude, one should consider all reasonably cogent evidence. This approach is being increasingly challenged, both scientifically and politically. The scientific challenge has come from methodologic views that focus on the randomized controlled trial (RCT) as the scientific gold standard, with priority being given, either to evidence from RCTs or to observational studies which closely mimic RCTs. The political challenge has come from various interests calling for the exclusion of epidemiological evidence from consideration by regulatory and advisory committees. This has been particularly motivated by anti-regulation “vested interests” which have disputed a long series of scientific discoveries, ranging from smoking and lung cancer to the reality of climate change. RESULTS:Recently, these pressures have led to calls for the exclusion of epidemiological evidence from consideration by regulatory and advisory committees, thereby weakening regulatory standards. This approach is typified by the (mis) use of scoring systems such as GRADE and ROBINS-I, which have been used to exclude important epidemiological evidence which does not fit the RCT paradigm. CONCLUSIONS:We need to return to a more pluralistic and inclusive approach, which considers all of the available evidence. KEYWORDS: evidence synthesis, environmental health

Arguments about face masks and Covid-19 reflect broader methodologic debates within medical science

There has perhaps been no issue as contentious in Covid-19 as face masks. The most contentious scientific debate has been between those who argue that “there is no scientific evidence”, by which they mean that there are no randomized controlled trials (RCTs), versus those who argue that when the evidence is considered together, “the science supports that face coverings save lives”. It used to be a ‘given’ that to decide whether a particular factor, either exogenous or endogenous, can cause a particular disease, and in what order of magnitude, one should consider all reasonably cogent evidence. This approach is being increasingly challenged, both scientifically and politically. The scientific challenge has come from methodologic views that focus on the randomized controlled trial (RCT) as the scientific gold standard, with priority being given, either to evidence from RCTs or to observational studies which closely mimic RCTs. The political challenge has come from various interests calling for the exclusion of epidemiological evidence from consideration by regulatory and advisory committees.

A platform trial in practice: adding a new experimental research arm to the ongoing confirmatory FLAIR trial in chronic lymphocytic leukaemia

BackgroundThe FLAIR trial in chronic lymphocytic leukaemia has a randomised, controlled, open-label, confirmatory, platform design. FLAIR was successfully amended to include an emerging promising experimental therapy to expedite its assessment, greatly reducing the time to reach the primary outcome compared to running a separate trial and without compromising the validity of the research or the ability to recruit to the trial and report the outcomes. The methodological and practical issues are presented, describing how they were addressed to ensure the amendment was a success.MethodsFLAIR was designed as a two-arm trial requiring 754 patients. In stage 2, two new arms were added: a new experimental arm and a second control arm to protect the trial in case of a change in practice. In stage 3, the original experimental arm was closed as its planned recruitment target was reached. In total, 1516 participants will be randomised to the trial.ResultsThe changes to the protocol and randomisation to add and stop arms were made seamlessly without pausing recruitment. The statistical considerations to ensure the results for the original and new hypotheses are unbiased were approved following peer review by oversight committees, Cancer Research UK, ethical and regulatory committees and pharmaceutical partners. These included the use of concurrent comparators in case of any stage effect, appropriate control of the type I error rate and consideration of analysis methods across trial stages. The operational aspects of successfully implementing the amendments are described, including gaining approvals and additional funding, data management requirements and implementation at centres.ConclusionsFLAIR is an exemplar of how an emerging experimental therapy can be assessed within an existing trial structure without compromising the conduct, reporting or validity of the trial. This strategy offered considerable resource savings and allowed the new experimental therapy to be assessed within a confirmatory trial in the UK years earlier than would have otherwise been possible. Despite the clear efficiencies, treatment arms are rarely added to ongoing trials in practice. This paper demonstrates how this strategy is acceptable, feasible and beneficial to patients and the wider research community.Trial registrationISRCTN Registry ISRCTN01844152. Registered on August 08, 2014

Molecular Landscape of Tp53 Mutations in Breast Cancer and Their Utility for Predicting Response to HER-Targeted Therapy in HER2 Amplification-Positive and HER2 Mutation-Positive Amplification-Negative Patients

Purpose: To determine the mutation rate of p53 in breast cancer and the predictive value for anti-HER2 treatment by ctDNA detection. Patients and Methods: The Tp53 mutation features were analyzed in Geneplus cohort (n=1,184). The MSK-BREAST cohort was used to explore the value of Tp53 for predicting the efficacy of anti-HER-2 antibody drugs. Then, next-generation sequencing was performed on ctDNA in phase Ib, phase Ic, phase II clinical trials of pyrotinib (HER2-amplification patients) and an investigator-initiated phase-II study of pyrotinib (HER2-mutant amplification-negative patients) to analyze the value of Tp53 for predicting the efficacy of HER2 TKIs. The MSK-BREAST cohort, MutHER cohort and SUMMIT cohort were used to verify our findings. Results: Tp53 mutations were detected in 53.1% (629/1,184) of patients in the Geneplus cohort. Tumors with Tp53 mutation showed a shorter PFS for anti-HER2 antibody treatment. However, no difference in PFS was shown for HER2 amplification-positive patients with different Tp53 statuses in the combination analysis of the pyrotinib phase Ib, phase Ic, and phase II clinical trials or the MSK-BREAST cohort. In patients with HER2 mutation and amplification negativity, Tp53 mutation-positive patients showed a trend for worse prognosis for anti-HER2 TKIs treatment than Tp53-wild-type patients in our investigator-initiated phase II study, and this trend was confirmed in the combined analysis of MutHER and SUMMIT cohorts. Conclusions: Tp53 gene mutation analysis can be used to identify biomarkers of anti-HER2 antibody drug resistance in HER2 amplification-positive patients and HER2 TKI resistance in HER2 mutation-positive and amplification-negative patients. Funding Statement: The present study was supported by the National Natural Science Foundation of China (No. 81874122) and Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (2017-I2M-3-004) Declaration of Interests: The authors declare that there are no competing interests. Ethics Approval Statement: All the studies were conducted in accordance with the Declaration of Helsinki and the principles of Good Clinical Practice and were approved by the Regulatory and Ethics Committees of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. All participants provided written informed consent.

Why using algorithms for evidence synthesis is wrong: triangulation is needed

The concept that one should consider all of the available evidence in order to decide whether a particular exposure can cause a particular disease has been increasingly challenged in recent years, both scientifically and politically. The scientific challenge has come from modern ‘causal inference’ methodologies which focus on the randomized controlled trial (RCT) as the scientific gold standard, with other types of evidence being downgraded by algorithm-based methods for evidence synthesis. One major example of this approach is the use of packaged algorithms for assessing studies, such as GRADE, and ROBINS. The political challenge has come largely from various vested interests (including industry) which have skillfully employed calls for greater accountability in science that have resonated in the present US administration – and supports methods that downgrade types of evidence that are inconvenient. This development has produced considerable concern about pressures to exclude most epidemiological evidence from consideration by regulatory and advisory committees, thereby weakening regulatory standards. In fact, modern ‘causal inference’ methods emphasizing emulations of randomized controlled trials (RCT) do not provide the gold standard, but are just a part of the epidemiological toolkit. Similarly, algorithm-based methods are just a part of the toolkit of methods that can be used for evidence synthesis. When used carefully, they may assist the assessment of possible biases in studies of some particular exposure-outcome associations. However, when used inappropriately to score studies, and to reject evidence on the basis of such scores, these algorithm-based systems have considerable potential for harm, both to science and to the public health.

Role of the institutions of provincial government in resolving social problems of the population of the Belarusian provinces (1861–1914)

The article describes the structure and powers of the provincial government in the implementation of the main directions of state social policy. It was noted that on theterritoryofBelarusthey played a major role in solving the social problems of the population due to the lack of zemstvos. The outdated legal framework and the lack of a clear division of functions hampered their effectiveness.In the mid 1880s regulatory committees were established in the structure of the provincial institutions. On the territory of the Belarusian provinces they played an important role in the implementation of social policy, as they controlled the financing of the rural­medical part and partly public charity. However, the experience of the activities of the regulatory committees was unsatisfactory. In this regard, at the end of the XIX century the Interior Ministry proposed to eliminate them, as well as to abolish the provincial food commissions and departments of public charity. It was planned to transfer their functions to the zemstvos. This proposal was implemented partially, as a result of the introduction of the institutions of local economy in theVitebsk,MinskandMogilevprovinces in 1903.At the end of the XIX century in the structure of the provincial administration ofBelaruswere created the offices which were entrusted with the functions of monitoring compliance with the workers’ legislation, and then the insurance of workers. They were formed under the influence of new social demands. These offices corresponded to new social and economic conditions, in contrast to the provincial institutions, which managed public charity, national food and health care.

The implementation of accurate pain reporting (APR) and placebo response reduction (PRR) training in clinical trials

Purpose: APR and PRR was developed in response to effective treatments failing to separate from placebo in phase II and III clinical trials. Training patients to report their symptoms more accurately has been shown to reduce variability in reporting as well as placebo response, thus increasing the difference in efficacy between arms. The objective of this study was to characterize how APR and PRR have been effectively implemented in clinical trials to date, with a specific focus on osteoarthritis studies. Methods: Components and the development of the APR and PRR training program were described methodically. Descriptive statistics were performed on clinical trials utilizing the training programs, such as indications, languages, subjects, and countries in which the training was successfully implemented. Results: The APR and PRR training programs were developed methodically using patient input, feedback, and cognitive debriefing studies, with the objective to provide information and train subjects and study staff about the importance of accurate pain reporting and to neutralize expectations in study. APR and PRR have been implemented in over 25 studies, 2,000 study sites, 34 countries, and 32 languages or dialects. The trainings have been utilized for 11 different indications with osteoarthritis being the most common with a total of 11 clinical trials. Conclusions: Training patients to accurately report their symptoms and to neutralize expectations has been found to reduce the placebo response and increase assay sensitivity. APR and PRR were systematically developed, tested, and have been adopted and viewed by many regulatory agencies and IRB committees worldwide.

Overview of non-innovator biological products in India

As per regulatory requirements, biosimilar drugs must show high similarity to their reference product in quality, preclinical and clinical tests. It is by these means that biosimilars are considered to be safe and efficacious. In India, any major deviation(s) from science-based principles in the manufacturing of a recombinant DNA-derived therapeutic biological product leads to its classification as a ‘non-innovator’ biological, which are approved as ‘New Drugs’. According to the World Health Organization (WHO), these biological products have uncertain safety and efficacy when compared to the reference biological and are therefore not recommended for use. However, these so-called non-innovator biological products continue to be developed in India, for reasons including brief and poorly implemented guidelines on biologicals, a lack of expertise on biosimilars amongst drug regulatory committees, lack of coordination among government departments working on biosimilars, poor quality accreditation in testing laboratories, and a lack of patent protection for innovator drugs. There is an urgent need to identify deficiencies in the ministries responsible for biosimilars in India, which could be through a scientific audit. Compliance with such an audit could strengthen the Indian regulatory system and thus increase the provision of affordable, high quality biosimilars in India.

Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda

Introduction: Yellow fever is endemic in specific regions of sub-Saharan Africa and the Americas, with recent epidemics occurring on both continents. The yellow fever vaccine is effective, affordable and safe, providing life-long immunity following a single dose vaccination. However, the vaccine production process is slow and cannot be readily scaled up during epidemics. This has led the World Health Organization (WHO) to recommend the use of fractional doses as a dose-sparing strategy during epidemics, but there are no randomized controlled trials of fractional yellow fever vaccine doses in Africa. Methods and analysis: We will recruit healthy adult volunteers, adults living with HIV, and children to a series of randomized controlled trials aiming to determine the immunogenicity and safety of fractional vaccine doses in comparison to the standard vaccine dose. The trials will be conducted across two sites; Kilifi, Kenya and Mbarara, Uganda. Recruited participants will be randomized to receive fractional or standard doses of yellow fever vaccine. Scheduled visits will include blood collection for serum and peripheral blood mononuclear cells (PBMCs) before vaccination and on various days – up to 2 years – post-vaccination. The primary outcome is the rate of seroconversion as measured by the plaque reduction neutralization test (PRNT 50) at 28 days post-vaccination. Secondary outcomes include antibody titre changes, longevity of the immune response, safety assessment using clinical data, the nature and magnitude of the cellular immune response and post-vaccination control of viremia by vaccine dose. Ethics and dissemination: The clinical trial protocols have received approval from the relevant institutional ethics and regulatory review committees in Kenya and Uganda, and the WHO Ethics Review Committee. The research findings will be disseminated through open-access publications and presented at relevant conferences and workshops. Registration: ClinicalTrials.gov NCT02991495 (registered on 13 December 2016) and NCT04059471 (registered on 15 August 2019).