Clinical Trials Of Medicinal Products Research Articles

Legal Regulation оf Insurance оf Clinical Trials оf Medicinal Products іn Ukraine

The article examines the current state and prospects of development of insurance for clinical trials of medicinal products in Ukraine, and also substantiates the need to introduce certain types of insurance in this area. As a result of a systematic analysis of current legislation, scientific literature and international acts, the author classifies persons participating in clinical trials of medicinal products into: 1) clinical trial subjects and 2) participants of such a scientific and medical experiment. In addition, the author outlines the main risks that arise for individual trial participants throughout the entire dynamics of clinical trials of medicines and proposes to minimize them by: changing the regulatory approach to making insurance mandatory by clarifying the subject matter of the insurance contract (insurance of liability of the investigator and sponsor of clinical trials); introduction of property insurance and liability insurance of manufacturers of medicinal products with state support; introduction of professional liability insurance of the investigator/co-investigator of clinical trials of medicinal products; introduction of insurance of investment and financial risks in the field of clinical trials of medicinal products with state support. It is also established that the peculiarities of the legal status of clinical trial participants, the specifics of their interests, and the need to participate in the trial influence the formation of the theory of multiple risks arising in the course of a clinical trial of a medicinal product and can be manifested as cases with negative consequences. The theory of multiple risks makes it possible to group them into different areas depending on the criterion of personalization (status of a person participating in a medical experiment: subject/ participant): 1) personal risks; 2) property risks; 3) liability risks.

Recommendations for the Clinical Development of Medicinal Products for Non-specific Influenza Chemoprophylaxis

INTRODUCTION. The evolution of the influenza virus has led to a gradual decrease in the effectiveness of current antivirals. Better methods of prevention, detection, control, and treatment of influenza are needed, including more effective vaccines and antivirals. At the moment, the Russian Federation and the Eurasian Economic Union lack documents regulating the conduct of clinical trials of medicinal products for influenza prevention and require that guidelines should be developed for the matter.AIM. The authors aimed to analyse the main regulatory approaches to preclinical and clinical development programmes for medicinal products for influenza prevention in the Russian Federation, the Eurasian Economic Union (EAEU), the European Union, and the United States of America.DISCUSSION. This review substantiates the importance of non-specific influenza chemoprophylaxis in reducing the risk of adverse outcomes of the disease. The authors analysed the main stages of preclinical development of medicinal products for influenza prevention and the potential contribution of preclinical studies to the planning of clinical trials. When developing preclinical and clinical programmes for medicinal products for influenza prevention, it is necessary, first of all, to take into account the requirements of the national good clinical practice guidelines and the EAEU guidelines for clinical trials in general. This article pays particular attention to the clinical trial designs used internationally, the possible options for their implementation, the characteristics of study populations, the formation of study groups, and the selection of primary and secondary endpoints.CONCLUSIONS. The article proposes approaches to planning and conducting clinical trials of medicinal products for the prevention of influenza, taking into account the specifics of legal norms and clinical traditions of Russian practice. These recommendations will ensure high-quality data on the effectiveness and safety of investigational medicinal products and accelerate the introduction of new effective medicinal products for influenza prevention into medical practice.

How can patient preferences be used and communicated in the regulatory evaluation of medicinal products? Findings and recommendations from IMI PREFER and call to action.

Objective: Patients have unique insights and are (in-)directly affected by each decision taken throughout the life cycle of medicinal products. Patient preference studies (PPS) assess what matters most to patients, how much, and what trade-offs patients are willing to make. IMI PREFER was a six-year European public-private partnership under the Innovative Medicines Initiative that developed recommendations on how to assess and use PPS in medical product decision-making, including in the regulatory evaluation of medicinal products. This paper aims to summarize findings and recommendations from IMI PREFER regarding i) PPS applications in regulatory evaluation, ii) when and how to consult with regulators on PPS, iii) how to reflect PPS in regulatory communication and iv) barriers and open questions for PPS in regulatory decision-making. Methods: PREFER performed six literature reviews, 143 interviews and eight focus group discussions with regulators, patient representatives, industry representatives, Health Technology Assessment bodies, payers, academics, and clincians between October 2016 and May 2022. Results: i) With respect to PPS applications, prior to the conduct of clinical trials of medicinal products, PPS could inform regulators' understanding of patients' unmet needs and relevant endpoints during horizon scanning activities and scientific advice. During the evaluation of a marketing authorization application, PPS could inform: a) the assessment of whether a product meets an unmet need, b) whether patient-relevant clinical trial endpoints and outcomes were studied, c) the understanding of patient-relevant effect sizes and acceptable trade-offs, and d) the identification of key (un-)favorable effects and uncertainties. ii) With respect to consulting with regulators on PPS, PPS researchers should ideally have early discussions with regulators (e.g., during scientific advice) on the PPS design and research questions. iii) Regarding external PPS communication, PPS could be reflected in the assessment report and product information (e.g., the European Public Assessment Report and the Summary of Product Characteristics). iv) Barriers relevant to the use of PPS in regulatory evaluation include a lack of PPS use cases and demonstrated impact on regulatory decision-making, and need for (financial) incentives, guidance and quality criteria for implementing PPS results in regulatory decision-making. Open questions concerning regulatory PPS use include: a) should a product independent broad approach to the design of PPS be taken and/or a product-specific one, b) who should optimally be financing, designing, conducting, and coordinating PPS, c) when (within and/or outside clinical trials) to perform PPS, and d) how can PPS use best be operationalized in regulatory decisions. Conclusion: PPS have high potential to inform regulators on key unmet needs, endpoints, benefits, and risks that matter most to patients and their acceptable trade-offs. Regulatory guidelines, templates and checklists, together with incentives are needed to foster structural and transparent PPS submission and evaluation in regulatory decision-making. More PPS case studies should be conducted and submitted for regulatory assessment to enable regulatory discussion and increase regulators' experience with PPS implementation and communication in regulatory evaluations.

More transparency in clinical research: How are the new transparency regulations assessed from the perspective of the pharmaceutical industry?

The year 2014 was aturning point for transparency in clinical research. Two regulatory innovations comprehensively changed the rules in the EU. For one thing, Regulation (EU) No.536/2014 on clinical trials of medicinal products for human use (Clinical Trials Regulation - CTR) came into force, and for another thing, Policy 0070 of the European Medicines Agency (EMA) on the publication of and access to clinical data was published. While the policy has been occupying the pharmaceutical industry in practice since 2015, the requirements of the CTR came into effect at the end of January 2022.The main innovation of the CTR is public access to the majority of documents and records that are created during the application process as well as during the course and after completion of aclinical trial. The special feature of Policy 0070 is the possibility for EU citizens to inspect the essential parts of amarketing authorisation application, such as the Clinical Study Report.This contribution to the discussion describes the completely new challenges in the area of transparency that the pharmaceutical industry is facing as aresult of the new requirements. In principle, transparency is to be welcomed in order to achieve the goals of the EU in the development and availability of medicines and vaccines. However, the protection of trade and business secrets of the pharmaceutical industry would be jeopardised. In the worst case, this could lead to adecline in investment in research and development within the scope of this regulation and to an international shift of clinical trials, including developing or emerging countries. Germany could lose more and more its leading role in conducting clinical trials in the EU.

Recommendations for the programme of clinical trials of medicinal products for the treatment of influenza

Scientific relevance. The development of new medicinal products to treat influenza is motivated by the limitations of existing treatment options, the emergence of drug resistance, and the health consequences of influenza epidemics associated with the highly contagious nature of the virus. Proper planning and implementation of clinical programmes providing reliable data on the efficacy and safety of medicinal products under development requires adherence to recommendations of the regulatory authorities. At the moment, the Russian Federation, the Eurasian Economic Union, and the European Union lack documented recommendations on conducting clinical trials of anti-influenza medicines. There is a need in national guidelines that will reflect the procedure for conducting clinical trials and establish the required amount of data to be submitted with marketing applications for new anti-influenza products.Aim. The study was aimed to analyse possible regulatory approaches to planning clinical development programmes for anti-influenza medicinal products.Discussion. The article pays particular attention to phase III studies, as the main studies confirming efficacy and safety. The authors described a clinical development strategy and the requirements for the volume and quality of efficacy and safety data. This article is based on the current Russian recommendations for the design and development of medicinal products and guidelines on their evaluation, as well as the recommendations by the U.S. Food and Drug Administration (FDA).Conclusions. The analysis results demonstrate the necessity for elaborating Russian recommendations for clinical studies of medicinal products for the treatment of influenza that will take into account the national legislation and clinical development practices. Such recommendations will streamline the implementation of new effective anti-influenza medicinal products.

Genome stability of the vaccine strain VACΔ6.

Due to cessation of mass smallpox vaccination in 1980, the collective immunity of humans against orthopoxvirus infections has virtually been lost. Therefore, the risk of spreading zoonotic human orthopoxvirus infections caused by monkeypox and cowpox viruses has increased in the world. First-generation smallpox vaccines based on Vaccinia virus (VAC) are reactogenic and therefore not suitable for mass vaccination under current conditions. This necessitates the development of modern safe live vaccines based on VAC using genetic engineering. We created the VACΔ6 strain by transient dominant selection. In the VACΔ6 genome, f ive virulence genes were intentionally deleted, and one gene was inactivated by inserting a synthetic DNA fragment. The virus was passaged 71 times in CV-1 cells to obtain the VACΔ6 strain from the VAC LIVP clonal variant. Such a long passage history might have led to additional off-target mutations in VACΔ6 compared to the original LIVP variant. To prevent this, we performed a genome-wide sequencing of VAC LIVP, VACΔ6, and f ive intermediate viral strains to assess possible off-target mutations. A comparative analysis of complete viral genomes showed that, in addition to target mutations, only two nucleotide substitutions occurred spontaneously when obtaining VACΔ4 from the VACΔ3 strain; the mutations persisting in the VACΔ5 and VACΔ6 genomes. Both nucleotide substitutions are located in intergenic regions (positions 1431 and 189738 relative to LIVP), which indicates an extremely rare occurrence of off-target mutations when using transient dominant selection to obtain recombinant VAC variants with multiple insertions/deletions. To assess the genome stability of the resulting attenuated vaccine strain, 15 consecutive cycles of cultivation of the industrial VACΔ6 strain were performed in 4647 cells certif ied for vaccine production in accordance with the “Guidelines for Clinical Trials of Medicinal Products”. PCR and sequencing analysis of six DNA fragments corresponding to the regions of disrupted genes in VACΔ6 showed that all viral DNA sequences remained unchanged after 15 passages in 4647 cells.

Impacts of COVID-19 Pandemic on the Conduct of Clinical Trials

The main objective of this study was to explore the effects of the coronavirus disease 2019 epidemic on the ongoing and upcoming all the clinical trials. The coronavirus (SARS-CoV-2) is a strain of Coronavirus that affected worldwide. The COVID-19 pandemic has Impacted all sectors of life including the conduct of clinical Trials of medicinal products globally. The COVID-19 had caused major disruptions to the all clinical trial mainly the non-COVID trails. An estimated 80% of non-COVID-19 trials were stopped or has been interrupted as a result of the COVID-19 pandemic.The effect of pandemic challenges will depend on the severity duration of each wave of the COVID 19 pandemic the duration of the trial. Therefore, in this study, we analysed the impact of COVID-19 on clinical trials, and alternative steps to continue non-COVID clinical trials.

Обзор руководства для комитетов по этике «Этическая экспертиза биомедицинских исследований: практические рекомендации» (третье издание, исправленное и дополненное) под общей редакцией А.Л. Хохлова

The article reviews the edition known as ‘Ethical Examination in Biomedical Research: Practical Considerations’ (third edition, revised and enlarged) under the general editorship of Professor Khokhlov AL, a corresponding member of the Russian Academy of Sciences. Due to a constantly growing number of clinical trials of medicinal products and improved level and quality of medical technologies, the role of an ethical examination aimed at compliance with ethical rights of trial participants and consumers, and safety aspects is increased. The article sums up what was described in the published edition.

Problems of criminal responsibility for violation of patient rights in the field of conducting clinacal trials of drugs

The article is devoted to the problem of criminal liability for violation of patients' rights in the field of clinical trials of medicines.
 The norms formulated in Articles 141 and 321-2 of the Criminal Code (hereinafter - the CC) of Ukraine are studied. It is established that the name of Art. 141 of the Criminal Code of Ukraine is unfounded in terms of the rules of legislative technique. The ambiguity of the phrase " violation of the patient's rights" does not reflect the content set forth in the disposition of Art. 141 of the Criminal Code of Ukraine prohibition. The list of patient rights is quite wide. However, the disposition of the article prohibits only three types of violations of patients 'rights, which can occur only in one of the possible areas of violations of patients' rights, namely in the field of clinical trials of medicines. In particular, liability is provided for: 1) for conducting clinical trials of drugs without the written consent of the patient or his legal representative; 2) for conducting clinical trials of medicinal products in relation to a minor; 3) for conducting clinical trials of drugs against incapacitated. In this case, liability arises only in the event of socially dangerous consequences (death of the patient or other serious consequences).
 Article 321-2 of the Criminal Code of Ukraine “Violation of the established procedure for pre-clinical studies, clinical trials and state registration of medicinal products” also provides for liability for violation of the procedure for clinical trials of medicinal products, but without causing death, other serious consequences (Part 1 and 2 Article 321-2 of the Criminal Code of Ukraine). However, sanctions under Art. 141 and Part 1 of Art. 321-2 of the Criminal Code of Ukraine are the same, and under Part 2 of Art. 321-2 of the Criminal Code of Ukraine - stricter.
 It is established that in part 3 of Art. 321-2 of the Criminal Code of Ukraine actually provides for liability for the same actions as in Art. 141 of the Criminal Code of Ukraine. However, the punishment under Part 3 of Art. 321-2 is much stricter than under Art. 141 of the Criminal Code of Ukraine. Emphasis is placed on the fact that there is competition between norms, in which more socially dangerous acts (which are provided for in Article 141) are punished less severely.
 Soundly the expediency of removing Art. 141 of the Criminal Code of Ukraine with the Criminal Code of Ukraine, as well as differentiation under Art. 321-2 of the Criminal Code of Ukraine liability for an act that is in gross violation of the order of clinical trials of drugs, led to the death of the patient.

Specificity of clinical trials of some osteoporosis medicines

Clinical trials of medicinal products related to the prevention and treatment of osteoporosis cover all activities, operations, methods and means for obtaining summary data and their interpretation in order to reveal the nature of the procedures, as well as certain relationships and dependencies of interest imposed the relevant study. The main objectives of the analysis are to characterize the relationships and dependencies, to measure the significance of these relationships, to model statistically significant relationships and dependencies. An important condition for conducting the statistical analysis is that the data are comparable, i.e. to be based on unambiguously defined features and criteria for their internal content. Objective: This work covers a documentary analysis of conducted clinical trials of drugs for the treatment of osteoporosis, as well as an analysis of the conducted clinical trials of the drug. Denosumab. Methods: Gathering primary empirical information, allowing for: objectification of certain facts; for retrospective study of events and phenomena in a long period; allows to determine the direction of development of the process of clinical trials and processes. The applied statistical analysis covers activities, operations, methods and means for obtaining summary data and for their interpretation in order to reveal the nature of the procedures, as well as certain connections and dependencies. Results: Studies show that clinical trials of osteoporosis products have the following limitations: gender differentiation – although the disease occurs in both sexes, studies in female patients are more common, patients are required to are in menopause, in some studies it is required as including criteria – the presence of a fracture due to osteoporosis, the age characteristic of patients is on average 45–80 years. All analyzed drugs show a positive effect on the state of bone density and bone structure. Conclusion: All analyzed medicinal products show a positive effect on the state of bone density and bone structure but the process is irreversible, so early prevention associated with early diagnosis would lead to earlier treatment measures in the early stages of the disease, which in turn, it would lead to long-term savings in indirect and difficult-to-estimate costs for society as a whole.

ПРОГАЛИНИ У РЕГУЛЯЦІЇ ПРОВЕДЕННЯ КЛІНІЧНИХ ДОСЛІДЖЕНЬ МЕДИЧНИХ ВИРОБІВ ТА МЕДИЧНИХ ВИРОБІВ ДЛЯ IN VITRO ДІАГНОСТИКИ В УКРАЇНІ

The article summarizes the arguments and counterarguments within the scientific debate on the issue of gaps in the regulation of clinical research of medical devices and medical devices for in vitro diagnostics in Ukraine. The main goal of the conducted research is to identify an exhaustive list of such gaps and develop recommendations for improving the mentioned regulations. The systematization of literary sources and approaches to solving the problem of gaps in the regulation of clinical research of medical devices and medical devices for in vitro diagnostics in Ukraine proved that the scientific discussion on this topic is not conducted in Ukraine, despite the presence of WHO recommendations on the revision of relevant legal acts . The urgency of solving this scientific problem lies in the fact that filling the gaps in the relevant regulations and harmonizing the regulations with the relevant regulations of the European Union is an integral part of the recognition of clinical evidence on the effectiveness and safety of medical devices obtained during research in Ukraine by European regulatory authorities. Filling these gaps could potentially lead to increased demand for clinical trials of medical devices and medical devices for in vitro diagnostics in Ukraine. The results of the empirical analysis of the market of clinical research of medical products in Ukraine, in comparison with clinical research of medicinal products in Ukraine, proved that Ukraine is more attractive for conducting clinical research of medicinal products. This trend is explained, in particular, by the presence of specialized regulation of clinical trials of medicinal products in Ukraine, the presence of a body responsible for supervision, audit, and evaluation of the results of such clinical trials. The study empirically confirms and theoretically proves that the regulation of this area is insufficient, which leads to the need for additional examination of research materials abroad, and therefore to lower interest in conducting clinical research of medical devices in Ukraine. The results of the conducted research may be useful to regulatory bodies for the development of a regulatory framework for conducting clinical trials of medical devices and products for in vitro diagnostics in Ukraine, sponsors of such trials and contractor companies performing such trials in Ukraine

A Study on the Human Panel Test of Health Functional Food

A health functional food is a product that has different functions from pharmaceuticals, and is a kind of food manufactured using raw materials or ingredients with useful functionalities for the human body. Scientific evidence is needed as to whether these health functional foods are functioning properly, such as maintaining or improving the actual health function or reducing the risk of disease, and whether they are safe for the human body. The process carried out to verify the functionality and safety of health functional foods is the human panel(application) test. Compared to the public s high interest in food safety, the safety of health functional food appears to have remained relatively outside the public s interest. So, the public s awareness of the significance and importance of human panel tests to confirm the safety or functionality of health functional foods seems to be lacking. As a result, acts or statutes to regulate human panel test of health functional foods have not been properly enacted, and the ｢Guideline for Human Panel Test Design｣ issued by the Ministry of Food and Drug Safety is only serving as a guideline. Health functional food has a character that is located halfway between foods and medicinal products(pharmaceuticals) in that it helps to maintain or promote functions beneficial to health. Accordingly, the legal discussion on human panel test of health functional food starts with deciding whether to classify health functional food as food or medicinal product. This is because, depending on the classification of food or medicinal product, the basic orientation or regulatory intensity for the legal regulation of human panel test is determined. In Korea, health functional foods are classified as food and do not require approval from the Minister of Food and Drug Safety to conduct human panel tests. But, it is designed to comply with the International Committee for Harmonization of Pharmaceutical Regulations - Good Clinical Practice of medicinal products or medical devices. However, in the case of health functional food, it cannot be treated in the same way as medicinal products in terms of hazard or risk to the human body. Ignoring each characteristic of health care products and uniformly applying clinical trial principles and ICH-GCP with the highest regulatory intensity can ultimately act as a factor hindering the development of the food industry. In short, in the human panel test of health functional food, a legal standard that is relaxed compared to the stringent ICH-GCP should be prepared separately. For example, in the case of human panel tests, it is necessary to improve the legal and institutional dimensions, such as differentiating clinical trial principles and/or GCP by reflecting the characteristics of health functional food, and simplifying the process of clinical trial conducts. On the other hand, the legal rules for the safety and protection of subjects will not be fundamentally different from clinical trials of medicinal products. The purpose of this study is to prepare a forum for a intensive discussion on human panel test of health functional foods, which has not received much attention in the field of law. To this end, we first examine the significance and procedure of human panel tests for health functional foods, analyze the current legal regulations on human panel tests and their limitations, and then conduct a comparative review of each country s human panel test system. Based on the derived various implications, we present a legal improvement plan for human panel test of health functional foods.

Planning a Clinical Trial Programme for Medicinal Products for the Treatment of Axial Spondyloarthritis

The criteria for diagnosis and classification of spondyloarthritides (SpAs) have undergone significant changes over the past 10 years. The emergence of new diagnostic methods and availability of new information on the prognosis of the disease outcome made it possible to distinguish a separate group of SpAs—axial SpA. Axial SpA is distinguished as a separate disease due to its high social significance, and special mechanisms of its development. The development of medicinal products for the treatment of axial SpA has some specific features, which requires preparation of specific recommendations for conducting clinical trials of such products. The aim of the study was to elaborate a methodological approach to clinical research and evaluation of efficacy and safety of medicinal products for systemic treatment of axial SpA. The study took into account the requirements/recommendations of the European Medicines Agency for planning clinical trials of medicinal products for the treatment of axial SpA, in order to streamline evaluation of national and foreign clinical trial results. The paper identifies the main stages of clinical trials, and proposes criteria for assessing product efficacy at each stage. It defines methods and tools for assessing clinical trial endpoints, which are necessary for evaluation of treatment effects. The paper describes specific aspects of clinical trial designs and their duration, and identifies the objectives of exploratory and confirmatory clinical trials. It also reviews treatment goals and treatment outcome evaluation. The study results could be used in elaboration of recommendations for clinical research of new medicinal products for axial SpA.

ECONOMIC FACTORS OF CLINICAL TRIALS OF MEDICINES IN SMALL POPULATION COUNTRIES: CASE STUDY OF LATVIA

The clinical trial process has become a significant type of services that provides huge added value to any national economy. Undoubtedly, the primary group of stakeholders in clinical trials of medicines is pharmaceutical companies that obtain a product as a result of successful clinical trials. However, other groups involved will also obtain materials and intangible benefits from the process of clinical trials of medicines. In this context, the authors tended to find out: What are considered to be the primary economic benefits of clinical trials of medicines in a society with small population? Aim of the research is to analyse economic factors of clinical trials of medicines in countries with small population, taking Latvia as an example. Object of the research: economic factors of clinical trials of medicines. The principle of snowball has been used to make the selection of the participants' survey. The empirical analysis and evaluation of economic factors in unique clinical trials of medicines are based on the qualitative research method of semi-structured individual (in-depth) interviews. According to the survey, the most important economic type of clinical trials of medicinal products in Latvia is “socioeconomic factors”, the average index of the factor being 0.82. The most significant three categories of the socioeconomic factors are “Access to the latest treatment methods and preparations” (Index max 1), “Improved patient care (time used per patient)” (Index 0.87) and “Exchange of experience, transfer of knowledge on the most innovative treatment methods” (Index 0.86). Society with small population values the primary economic benefits from clinical trials of medicines. It can be concluded that the socioeconomic factor is the most significant, compared to the direct economic factor and the alternative cost savings factor.

Current Approaches to Planning and Conducting Clinical Trials of Medicinal Products for the Treatment of Crohn's Disease

Accumulation of knowledge on Crohn’s disease, and development of biological products intended for the treatment of its underlying cause formed the basis for the development of objective methods for assessing the intensity of the pathological process, which in turn affected scientific approaches to the planning of clinical trials in this field. To date, many international recommendations related to planning, conduct of clinical trials, and analysis of their results, have been updated. Considerable experience has been gained with clinical trials of medicines intended for the treatment of Crohn’s disease. Therefore, the methodological approach to the planning of pivotal clinical studies needs to be reviewed. The aim of the study was to develop requirements for planning and expert evaluation of clinical trials conducted with the aim of obtaining marketing authorisation for medicinal products for the treatment of Crohn’s disease. The paper analyses regulations, recommendations, and scientific literature on the treatment of Crohn’s disease and describes the methodology for planning clinical trials. It describes the evolution of approaches to clinical research planning since biological medicines appeared. The authors substantiate the need for an integrated concept of clinical research, which covers goals, estimated therapeutic effect, design, and choice of the statistical analysis method. They also provide scientific arguments in favour of a combined primary endpoint including endoscopic remission and the assessment of treatment results by the patient. The paper lists patient eligibility criteria in terms of “inducing and/or maintaining remission of the disease”. The authors analyse the main intercurrent events, their influence on the therapeutic effect, and propose approaches to the planning of endpoints, including assessment of intercurrent events. The paper highlights the fact that the principles of planning and conducting Phase III clinical trials need to be consistent with the evidence-based strategies of reducing the risk of incorrect assessment of efficacy and safety of new medicines, and that the obtained results have to meet the requirements of the regulatory authorities at the stage of marketing authorisation.

CONTRACTUAL REGISTRATION OF ORGANIZATIONAL AND LEGAL RELATIONS BETWEEN SUBJECTS INVOLVED IN THE CONDUCT OF CLINICAL TRIALS OF MEDICINAL PRODUCTS

The aim: Determination of features of contractual registration of organizational and legal relations between the subjects involved in carrying out clinical trials of medicinal products; justification of proposals on improvement of law enforcement practice in this field. Materials and methods: This research is based on the analysis of the norms of international law and legislation of particular states, practice of contractual registration of organizational and legal relations between the subjects of clinical trials of medicinal products. The research was carried out using the methods of dialectical and formal logic, general scientific and special legal research methods. Conclusions: Two models of contractual registration of organizational and legal relations between the subjects involved in clinical trials of medicinal products were justified, and law enforcement recommendations for the contractual registration of such relationships, ensuring that the clinical trial is in compliance with international regulations and ethics in this field, were given.

Main changes in European Clinical Trials Regulation (No 536/2014).

The new Regulation (EU) No. 536/2014 for clinical trials of medicinal products for human is part of a European regulatory framework in which the European Commission has wished to give a strong impetus to scientific research and industrial progress. It is a new regulation that fills a series of regulatory gaps in the Clinical Trials through the creation of a uniform framework for the authorization of clinical trials by all interested Member States with a single assessment of the results. The Regulation thus facilitates cross-border cooperation to make the clinical tests wider and encourage the development of special treatments, for example for rare diseases, but above all streamlines the rules on clinical trials across European Union (EU), introducing simplified rules for experimentation so-called 'low level of intervention', on which much has been discussed and still arouses concern, providing for authorized medicines or used off-label in the presence of scientific evidence published on efficacy and safety and to benefit from they will be mainly the pediatric and oncological therapeutic areas. The applications and any communication will be submitted paperlessly via a new electronic EU portal. The complex processing procedures and shorter time limits are to be stressed in comparison to the previously valid regulations. This is a major challenge for all stakeholders, but on the other hand it should contribute to the future role of the EU in the development of innovative medicines.

A harmonized and efficient clinical research environment would benefit patients and enhance European competitiveness. Commentary.

The forthcoming implementation of the European Clinical Trial Regulation (Regulation (EU) No. 536/2014), which is expected to facilitate the conduct of clinical trials across the European Union, will require National Authorities to create the best conditions for the implementation of the new Regulation through national guidelines, so that sponsors may reconsider Europe as a prime location for planning clinical trials. During a meeting titled "Innovation in Clinical Research", an expert panel discussed potential local advances fostering competitiveness of European clinical research with representatives of the pharmaceutical industry, patient organisations and Italian regulatory agency in view of the forthcoming implementation of (EU) No. 536/2014 on clinical trials of medicinal products. In this article we summarise the findings of the meeting, describe features characterising clinical research patterns and offer some suggestions on the possible involvement of all stakeholders in order to foster research innovation and allow the timely access to novel medicines for patients.

Research involving adults lacking capacity to consent: the impact of research regulation on 'evidence biased' medicine.

BackgroundSociety is failing in its moral obligation to improve the standard of healthcare provided to vulnerable populations, such as people who lack decision making capacity, by a misguided paternalism that seeks to protect them by excluding them from medical research. Uncertainties surround the basis on which decisions about research participation is made under dual regulatory regimes, which adds further complexity. Vulnerable individuals’ exclusion from research as a result of such regulation risks condemning such populations to poor quality care as a result of ‘evidence biased’ medicine.Main TextThis paper explores the research regulation provisions for proxy decision making for those unable to provide informed consent for themselves, and the subsequent legal and practical difficulties for decision-makers. There are two separate regulatory regimes governing research involving adults who lack capacity to consent in England and Wales. The Mental Capacity Act 2005 governs how incapacitated adults can be involved in research, however clinical trials of medicinal products are separately regulated by the Medicines for Human Use (Clinical Trials) Regulations 2004. There are significant differences under these dual regimes in the provisions for those lacking capacity to participate in medical research. The level of risk permitted differs, with a greater requirement for justification for participation in a clinical trial than other types of research. Who acts as proxy decision maker, how much information is provided to the person lacking capacity, and whether they retain the power of veto also significantly differs.ConclusionThe development of two separate regulatory regimes has resulted in significant differences between the provisions for clinical trials and other forms of research, and from usual medical practice. The resulting uncertainty has reinforced the tendency of those approving and conducting research to exclude adults lacking capacity to avoid difficult decisions about seeking consent for their participation. Future developments, such as the incoming EU Regulations, may address some of these differences, however the justification and level of risk permitted requires review to ensure that requirements are appropriate and proportionate to the burdens and risks for the individual, and also to the benefits for the wider population represented.

Blindingly obvious (once revealed): a novel approach to blinding medicinal products for injection

Background Blinding is a pre-requisite to high standard clinical trials of medicinal products (CTIMPs), but this requirement, can on occasions, present complex challenges in placebo matching and delivery. OBS2 is a trial evaluating the effectiveness of early fibrinogen administration in the management of complex postpartum haemorrhage. Fibrinogen concentrate is a white powder that froths distinctively on reconstitution and a suitable placebo, that could match these characteristics, could not be identified during the trial design stage.