Multinational Clinical Research Research Articles

Ethical Considerations in Conducting Research on Autism Spectrum Disorders in Low and Middle Income Countries

Autism spectrum disorder (ASD) is being identified in an ever-increasing number of countries, including many that are low or middle income (LMIC). Research conducted in these countries requires awareness of unique ethical issues. Drawing on the experience of two organizations that have been involved in conducting and collaborating in ASD research in India, we describe specific considerations in conducting epidemiological, genetic and treatment studies as well as general principles from the field of multinational clinical research as they apply to the conduct of ASD research. We argue that greater attention to ethical concerns will result in quality studies conducted in LMICs that are also of greatest relevance for families and children with ASD.

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries.

BackgroundIn order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.MethodsWe conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.ResultsOur results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.ConclusionThe Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.

A European perspective – the European clinical research infrastructures network

Evaluating research outcomes requires multinational cooperation in clinical research for optimization of treatment strategies and comparative effectiveness research, leading to evidence-based practice and healthcare cost containment. The European Clinical Research Infrastructures Network (ECRIN) is a distributed ESFRI (European Strategy Forum on Research Infrastructures) roadmap pan-European infrastructure designed to support multinational clinical research, making Europe a single area for clinical studies, taking advantage of its population size to access patients, and unlocking latent scientific potential. Servicing multinational trials started during its preparatory phase, and ECRIN will now apply for an ERIC (European Research Infrastructures Consortium) status by 2011. By creating a single area for clinical research in Europe, this achievement will contribute to the implementation of the Europe flagship initiative 2020 ‘Innovation Union’, whose objectives include defragmentation of the research and education capacity, tackling the major societal challenges starting with the area of healthy ageing, and removing barriers to bring ideas to the market.

Adaptation of the Audit of Diabetes-Dependent Quality of Life questionnaire to people with diabetes in China

Aim This study was intended to cross-culturally adapt and evaluate the Chinese version of the Audit of Diabetes Dependent Quality of Life (ADDQoL) – the Chinese Normal Audit of Diabetes-Dependent Quality of Life (CN-ADDQoL) in Mainland, China. Methods The standard procedure for cross-culture adaptation was used to develop the Chinese version CN-ADDQoL. After the linguistic validation, the validity and reliability of CN-ADDQoL questionnaire were evaluated based on a sample of 697 Type 2 diabetes patients. The Cronbach's α coefficient, correlation analysis and the structural equation model (SEM) were applied, respectively. Results We developed 19 items for the CN-ADDQoL questionnaire. The estimated Cronbach's α coefficient was 0.941, indicating an excellent internal consistency of the scale. All items had high performance in the structural validity evaluation, with most factor loading values being larger than 0.40 (varied from 0.44 to 0.88). Conclusions The Chinese version CN-ADDQoL has maintained its original psychometric properties and achieved adequate reliability and validity. Therefore, it could be efficiently used to evaluate the current trend of diabetes self-management education programs and multinational clinical research trials.

Translation and standardization of the HoNOSCA (Health of the Nation Outcome Scales for Children and Adolescents) scale in a Greek sample

The Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) is a brief measure of outcomes. Evidence for the effectiveness of patient treatments conducted in mental health services is limited in Greece. Thus, in an attempt to employ an easily administered and valid outcome measure, to assess outcomes in clinical practice for children and adolescents, but also to be able to compare the results across countries, the HoNOSCA was the measure of choice. In this study we have translated and validated it in a Greek sample. We have investigated the inter-rater reliability, intraclass correlation, concurrent validity, and clinical change across time, of the HoNOSCA Greek translation. The results show that the Greek translation of HoNOSCA is a reliable and valid instrument. It can be used for clinical, managerial, research and audit purposes, but, most importantly, to facilitate multinational clinical research and comparison of data with other countries.

ECRIN (European Clinical Research Infrastructures Network) et la structuration de la recherche clinique en Europe

Clinical research plays a key role both in the development of innovative health products and in the optimisation of medical strategies, leading to evidence-based practice and healthcare cost containment. ECRIN is a distributed ESFRI-roadmap pan-European infrastructure designed to support multinational clinical research, making Europe a single area for clinical studies, taking advantage of its population size to access patients, and unlocking latent scientific providing services to multinational. Servicing of multinational trials started during the preparatory phase, and ECRIN has applied for ERIC status in 2011. In parallel, ECRIN has also proposed an FP7 integrating activity project to further develop, upgrade and expand the ECRIN infrastructure built up during the past FP6 and FP7 projects, facilitating an efficient organization of clinical research in Europe, with ECRIN developing generic tools and providing generic services for multinational studies, and supporting the construction of pan-European disease-oriented networks that will in turn act as ECRIN users. This organization will improve Europe's attractiveness for industry trials, boost its scientific competitiveness, and result in better healthcare for European citizens. The three medical areas supported in this project (rare diseases, medical devices, and nutrition) will serve as pilots for other biomedical research fields. By creating a single area for clinical research in Europe, this structure will contribute to the implementation of the Europe flagship initiative 2020 'Innovation Union', whose objectives include defragmentation of research and educational capacities, tackling the major societal challenges (starting with healthy aging), and removing barriers to bringing ideas to the market.

Some Recent Developments in the International Guidelines on the Ethics of Research Involving Human Subjectsa

We are in a period of reconsideration and revision of international ethical guidelines for the conduct of biomedical research involving human subjects. The proximate cause of much of this activity is the recent controversy over the ethics of the use of a placebo control in the clinical trials of the short-duration regimen of zidovudine for prevention of perinatal transmission of HIV infection, trials that were carried out in several so-called technologically developing countries. Critics of these trials claimed that they were in violation of Article II.3 of the Declaration of Helsinki, which states: "In any medical study, every patient--including those of a control group, if any--should be assured of the best proven diagnostic and therapeutic method. This does not exclude the use of inert placebo in studies where no proven diagnostic or therapeutic method exists." The critics claimed that since the "best proven ... method" is the 076 regimen, this is what must be provided to members of the control groups. Failure to do so, they asserted, was a serious breach of ethics. In response to this allegation, several major international and national agencies convened multidisciplinary groups to consider the ethics of multinational clinical research. The first thing they realized was that Article II.3 was in error in that it did not reflect contemporary ethical thinking. Moreover, it was routinely violated in research conducted in developed as well as in developing countries. What replaces this standard? The 1993 CIOMS International Ethical Guidelines for Biomedical Research Involving Human Subjects include several criteria for justification of research carried out in developing countries. Most importantly, the research must be responsive to the health needs and priorities of the host country. They also require that any therapeutic products developed in such research must be made "reasonably available" to residents of the host country. A new standard is emerging for selecting therapies to be administered to participants in multinational clinical trials and for use as the control "treatment" in such trials. It is called the "highest attainable and sustainable" therapeutic method. Application of this standard differs from application of the "best proven method" standard in that it permits the evaluation of new therapies that are responsive to the health needs and priorities of resource-poor countries. It has long been recognized that the Declaration of Helsinki is a flawed document in that it relies on the illogical distinction between therapeutic and nontherapeutic research. This distinction has been removed from the most recent draft revisions of the Helsinki and the CIOMS documents.

The Pediatric Research Initiative in the United States: Implications for Global Pediatric Research

Recognition of cultural and ethnic differences in target populations for drugs, an increase in multi-country new drug application submissions, harmonization of international regulatory requirements and research guidelines, and the availability of multinational contract research organizations (CROs) will facilitate the current trend toward increased multinational clinical research trials. Currently, approximately 20% of research by United States-based companies is already conducted outside the United States. Since new drug applications submitted to the United States Food & Drug Administration (FDA) will require pediatric studies for any drugs with potential use in the pediatric population, it is likely that they will be done by any drug sponsor planning to enter its product in the United States market at some point in the product’s life cycle regardless of the country of origin. Although the current United States domestic market for pediatric drugs is considered small, nearly 20% of all drug sales in developed countries worldwide are for patients under 18 years of age. The pediatric drug market in developing countries may be just as important. It has been estimated that by the year 2000, developing countries, where more than half of the population are children, will comprise 36% of the world market for pharmaceuticals. Establishment of international standards for pediatric drug development, currently in process by the International Conference on Harmonization (ICH), should eventually result in availability of consistent formulations of needed therapeutic drugs for all children worldwide.

Classification of primary headaches

In 1988, the International Headache Society (IHS) classification committee published operational diagnostic criteria for the primary headaches and a broad range of other headache disorders. These criteria have been translated into more than ten languages, providing uniform terminology for clinical practice, multinational clinical trials, and biologic and epidemiologic research. The criteria have also been evaluated in a number of field studies intended to address their generalizability, exhaustiveness, reliability, and validity. In the present publication the IHS criteria for migraine and tension-type headache are presented.

Multinational Drug Development and Clinical Research: A Bird's Eye View of Principles and Practice

The development of a new molecular entity (NME) into a drug can only be successful if the drug meets today's standards in terms of quality, efficacy, safety, and convenience. The better a new drug meets hitherto unmet therapeutic needs, the more successful it will be. Urgent needs for new drugs exist in the areas of chronic diseases. Safety requirements for drugs to be used chronically are paramount. Assessments of the therapeutic benefit as opposed to the risks of a new drug are important criteria for approval. As a consequence of these strict requirements which have precipitated in rules and regulations for biomedical testing and marketing approval in most countries of the world, the drug development process has expanded and in many instances leaves little of the effective patent life to recover the considerable investment needed for an innovation. The ethical and scientific principles of drug development and biomedical research are summarized in a highly condensed manner in the Declaration of Helsinki....

What makes multinational clinical research ethical & how to minimize possible exploitation in host country?

BACKGROUND: In recent years there has been substantial debate about the ethics of research in developing countries. The controversies have been centered on (i) standard of care that should be used in research (ii) reasonable availability of interventions that are proven to be useful and (iii) quality of informed consent. Clinical research is different from clinical practice in ethically important ways where each has different goals, different methods and different justification for risk to individuals. The goal of clinical research is to generate useful knowledge about health and illness. Benefit to participants is not the purpose of research, although it does occur. Here people are the means to develop useful knowledge; and are thus at risk of exploitation. DOI: http://dx.doi.org/10.3329/bioethics.v2i2.9541 Bangladesh Journal of Bioethics 2011; 2(2): 20-23