Clinical Research and Regulatory Affairs最新文献_第2页

Linezolid in South Africa: The regulatory authority’s role in supporting access to improved treatment regimens for drug-resistant tuberculosis 南非的利奈唑胺:监管机构在支持获得改进的耐药结核病治疗方案方面的作用

Clinical Research and Regulatory Affairs Pub Date : 2015-09-18 DOI: 10.3109/10601333.2015.1079216

Julia Hill

{"title":"Linezolid in South Africa: The regulatory authority’s role in supporting access to improved treatment regimens for drug-resistant tuberculosis","authors":"Julia Hill","doi":"10.3109/10601333.2015.1079216","DOIUrl":"https://doi.org/10.3109/10601333.2015.1079216","url":null,"abstract":"Abstract The rising incidence of drug-resistant tuberculosis (DR-TB) in South Africa is cause for concern, with doctors having limited treatment options to offer patients who face excruciating side-effects from existing medications, and poor odds of treatment success. With several newer drugs showing efficacy against DR-TB, increased possibilities exist to stem the tide of the epidemic, shorten treatment duration, and improve outcomes. To take advantage of this potential TB treatment revolution, countries must rapidly facilitate access to existing and future drugs. This requires co-ordinated action from governments, and particularly regulatory authorities, in promoting early access to new treatments, tackling intellectual property and price barriers, expediting regulatory approval, adopting and implementing up-to-date TB management policies, and engaging with research and development processes for new regimens. Doctors Without Borders expended great effort to obtain a less expensive version of the drug, linezolid, for its DR-TB pilot program in Khayelitsha, South Africa. This piece describes that experience, and subsequently offers recommendations for policy reforms which could help South Africa more rapidly access other new TB drugs in the future. The South African experience may be of relevance to other countries seeking advice on how to facilitate access to new treatments and tackle their TB epidemics.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85172003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

The regulation of fecal microbiota for transplantation: An international perspective for policy and public health 粪便微生物群对移植的调节:政策和公共卫生的国际视角

Clinical Research and Regulatory Affairs Pub Date : 2015-07-03 DOI: 10.3109/10601333.2015.1046602

Carolyn Edelstein, Z. Kassam, J. Daw, Mark B. Smith, C. Kelly

{"title":"The regulation of fecal microbiota for transplantation: An international perspective for policy and public health","authors":"Carolyn Edelstein, Z. Kassam, J. Daw, Mark B. Smith, C. Kelly","doi":"10.3109/10601333.2015.1046602","DOIUrl":"https://doi.org/10.3109/10601333.2015.1046602","url":null,"abstract":"Abstract Clostridium difficile is the most common hospital-acquired pathogen in the US, and recurrent C. difficile infection (CDI) is a major public health issue. Twenty per cent of CDI patients experience recurrence, and their risk of recurrence rises with each failure to achieve clinical resolution. Fecal microbiota transplantation (FMT) is a remarkably efficacious treatment for recurrent CDI. However, national health agencies are grappling with the appropriate regulatory paradigm to apply to this innovative treatment. Current FMT regulations in the US, Canada, Western Europe, Australia, and China are in varying degrees of flux, although many regulators are choosing to apply the drug and biologic framework. FMT regulations should allow recurrent CDI patients safe access to this treatment as research continues. Regulating FMT like a drug or biologic, although most convenient from a legal perspective, overly restricts access while under-regulating the methods by which the stool is screened, processed, stored, and used. Human tissue and tissue-based products regulations could achieve the desired level and kind of oversight, but fecal microbiota for transplantation fail to meet applicable statutory definitions. A custom regulatory solution would be more appropriate, but many pathways that regulators may take to achieve this goal require time and resources for health agencies to develop.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87888578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Inter-ethnic differences in drug response: Implications for drug development and complying with drug regulation 药物反应的种族间差异:对药物开发和遵守药物监管的影响

Clinical Research and Regulatory Affairs Pub Date : 2015-07-03 DOI: 10.3109/10601333.2015.1064131

R. Shah

{"title":"Inter-ethnic differences in drug response: Implications for drug development and complying with drug regulation","authors":"R. Shah","doi":"10.3109/10601333.2015.1064131","DOIUrl":"https://doi.org/10.3109/10601333.2015.1064131","url":null,"abstract":"Abstract The two key components of the pharmacology of a drug—dose–concentration (pharmacokinetic) and/or concentration–response (pharmacodynamic) relationships—are often influenced by genetic variations. These account for a substantial fraction of variability in dose–response or drug response, not only between individuals, but also between different ethnic groups. The approval of ‘BiDil’ for the treatment of cardiac failure in self-identified black patients is a spectacular example of inter-ethnic differences in drug response and regulatory awareness of ethnicity of the study population. Drug development programs are increasingly undertaken globally to reduce costs, shorten timeframes, and address issues concerning global prescribing. Regulatory authorities have responded to this globalization of drug development by promulgating guidelines that recommend sponsors of new drugs to explore the role of genetic variations, and potential differences in drug response, between different ethnic populations. They may refuse to accept an application, or require bridging studies, when such differences are anticipated but not adequately addressed. These bridging studies may include (i) pharmacokinetic studies, (ii) pharmacodynamic studies, (iii) dose–response studies, and/or (iv) in extreme cases, pivotal phase III studies in order to extrapolate efficacy and/or safety data from one population to another.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85379053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Evaluating the impacts of the FDA’s guidance for patient-reported outcomes (PROs) measures on clinical trial-based approved drug product labeling claims, 2006–2014 评估2006-2014年FDA关于基于临床试验的批准药品标签声明的患者报告结果(PROs)措施指南的影响

Clinical Research and Regulatory Affairs Pub Date : 2015-07-03 DOI: 10.3109/10601333.2015.1064441

A. Palsgrove

{"title":"Evaluating the impacts of the FDA’s guidance for patient-reported outcomes (PROs) measures on clinical trial-based approved drug product labeling claims, 2006–2014","authors":"A. Palsgrove","doi":"10.3109/10601333.2015.1064441","DOIUrl":"https://doi.org/10.3109/10601333.2015.1064441","url":null,"abstract":"Abstract The FDA’s Guidance for Industry, Patient-Reported Outcomes (PRO) Measures: Use in Medical Product Development to Support Labeling Claims (i.e. “PRO Guidance”; 2009) outlines the agency’s perspectives on how PRO measures, used to support efficacy end-points in therapeutics clinical trial programs, may be evaluated by the FDA. Prior reviews have attempted to identify PRO-based statements in product labels in order to evaluate the potential impacts of the PRO guidance on the rate of approvals of PRO-based claims, but none have been enacted after 2010. An in-depth search identified drug product labels approved by the FDA from January 2006 through to December 2014, with efficacy statements supported by PRO measures. Drug product labels were sorted by chemical type and year of approval, and the differences between time periods before and after the finalization of the PRO Guidance were reviewed with statistical tests. Results showed a reduction in the overall approvals of label-based efficacy statements supported by PRO measures after 2009, which may indicate that fewer phase 3 clinical trial programs have met agency benchmarks for the inclusion of subjective assessments as primary or secondary end-points in support of therapeutic efficacy.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81901120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Challenges of risk-based monitoring of clinical trials 基于风险的临床试验监测的挑战

Clinical Research and Regulatory Affairs Pub Date : 2015-07-03 DOI: 10.3109/10601333.2015.1046990

M. Simović, N. Nikolić

{"title":"Challenges of risk-based monitoring of clinical trials","authors":"M. Simović, N. Nikolić","doi":"10.3109/10601333.2015.1046990","DOIUrl":"https://doi.org/10.3109/10601333.2015.1046990","url":null,"abstract":"Abstract The oversight of monitoring activities in clinical trials generally comes from the ICH GCP Guidelines and covers a wide range of responsibilities: trial progress oversight, adherence to the Study Protocol, Standard Operating Procedures, Good Clinical Practice, applicable regulatory requirement(s) and Source Data verification vs accuracy and completeness of the Case Report Form entries. Risk-based monitoring was developed and adopted by Sponsors, Investors, and CROs to decrease the costs of clinical trials and make study management more effective. Both the EMA and the FDA support such an approach with their papers. Interestingly, the review of the EMA “Annual report of the GCP Inspectors working group in 2012” has consistently shown persistence of a significant number of findings in fields/areas of monitoring that cannot be fully or partially captured with a centralized or targeted monitoring approach and cannot be identified, such as essential documents, presence and adherence to SOPs, trainings, and the quality of source documentation. Such results open up new challenges for Sponsors, CROs, and other stakeholders. As long as all current ICH GCP Guidelines are a cornerstone of clinical research, monitoring plans and risk assessments will include overseeing a significant pool of additional aspects, apart from the SDV.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80553614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Opportunities to improve clinical trial design in urothelial bladder cancer 改善尿路上皮性膀胱癌临床试验设计的机会

Clinical Research and Regulatory Affairs Pub Date : 2015-04-03 DOI: 10.3109/10601333.2015.1022282

J. Chiu, S. Sridhar

{"title":"Opportunities to improve clinical trial design in urothelial bladder cancer","authors":"J. Chiu, S. Sridhar","doi":"10.3109/10601333.2015.1022282","DOIUrl":"https://doi.org/10.3109/10601333.2015.1022282","url":null,"abstract":"Abstract Treatment of urothelial cancer (UC) has seen limited advances over the last three decades. As new agents become available, a critical look at trial design across the spectrum of UC is needed. Early UC trials should aim to stratify patients by risk level, defined by molecular features to reduce the heterogeneity and improve interpretation of trial results. For muscle invasive UC, the practice of neoadjuvant chemotherapy should be encouraged, especially as complete pathological response could be used as a surrogate end-point measure on trials and has the potential for garnering expedited drug approval. The neoadjuvant setting also provides a unique opportunity for evaluating biomarkers and targeted therapy given the availability of tumor tissue. For advanced disease, more emphasis should be placed on studies for patients who are cisplatin-ineligible or have poorer performance status, which represents many UC patients. Bladder-sparing therapy, incorporating agents targeting the HER2 or PI3K/AKT/mTOR pathway, or immunotherapy are potential new directions in UC. The importance of quality-of-life as an end-point in clinical trials in UC should also not be overlooked. Ultimately, multidisciplinary large-scale collaborations will be the key to move this field forwards.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73612859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EU regulatory guidelines for the clinical evaluation of adjuvants 辅助剂临床评价的欧盟法规指南

Clinical Research and Regulatory Affairs Pub Date : 2015-04-03 DOI: 10.3109/10601333.2015.1001899

B. Klug, P. Celis, Robin Ruepp, J. Robertson

引用次数: 2

Clinical trial design methodologies for advanced sarcoma therapy 晚期肉瘤治疗的临床试验设计方法

Clinical Research and Regulatory Affairs Pub Date : 2015-04-03 DOI: 10.3109/10601333.2015.1012209

B. Petek, S. Pollack, A. Constantinidou, Robin L. Jones

引用次数: 0

Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel. 经颅直流电刺激（tDCS）临床和研究使用的监管考虑因素：专家小组的审查和建议。

Clinical Research and Regulatory Affairs Pub Date : 2015-03-01 DOI: 10.3109/10601333.2015.980944

F Fregni, M A Nitsche, C K Loo, A R Brunoni, P Marangolo, J Leite, S Carvalho, N Bolognini, W Caumo, N J Paik, M Simis, K Ueda, H Ekhitari, P Luu, D M Tucker, W J Tyler, J Brunelin, A Datta, C H Juan, G Venkatasubramanian, P S Boggio, M Bikson

{"title":"Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel.","authors":"F Fregni, M A Nitsche, C K Loo, A R Brunoni, P Marangolo, J Leite, S Carvalho, N Bolognini, W Caumo, N J Paik, M Simis, K Ueda, H Ekhitari, P Luu, D M Tucker, W J Tyler, J Brunelin, A Datta, C H Juan, G Venkatasubramanian, P S Boggio, M Bikson","doi":"10.3109/10601333.2015.980944","DOIUrl":"10.3109/10601333.2015.980944","url":null,"abstract":"<p><p>The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. We therefore convened a group of research and clinician experts on tDCS to review the research and clinical use of tDCS. In this report, we review the regulatory status of tDCS, and we summarize the results according to research, off-label and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan and United States. Research use, off label treatment and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials.</p>","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431691/pdf/nihms-646440.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33310564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adaptive designs for comparative effectiveness research trials 比较有效性研究试验的适应性设计

Clinical Research and Regulatory Affairs Pub Date : 2015-01-02 DOI: 10.3109/10601333.2014.977490

John Kairalla, C. Coffey, Mitchell A. Thomann, R. Shorr, K. Muller

{"title":"Adaptive designs for comparative effectiveness research trials","authors":"John Kairalla, C. Coffey, Mitchell A. Thomann, R. Shorr, K. Muller","doi":"10.3109/10601333.2014.977490","DOIUrl":"https://doi.org/10.3109/10601333.2014.977490","url":null,"abstract":"Abstract Medical and health policy decision-makers require improved design and analysis methods for comparative effectiveness research (CER) trials. In CER trials, there may be limited information to guide initial design choices. In general settings, adaptive designs (ADs) have effectively overcome limits on initial information. However, CER trials have fundamental differences from standard clinical trials including population heterogeneity and a vaguer concept of a “minimum clinically meaningful difference”. The objective of this article is to explore the use of a particular form of ADs for comparing treatments within the CER trial context. To achieve this, the authors review the current state of clinical CER. They also identify areas of CER as particularly strong candidates for application of novel AD and illustrate the potential usefulness of the designs and methods for two group comparisons. The authors found that ADs can stabilize power. Furthermore, the designs ensure adequate power for true effects are at least at clinically significant pre-planned effect size, or when variability is larger than expected. The designs allow for sample size savings when the true effect is larger or when variability is smaller than planned. The authors conclude that ADs in CER have great potential to allow trials to successfully and efficiently make important comparisons.","PeriodicalId":10446,"journal":{"name":"Clinical Research and Regulatory Affairs","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91273927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0