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The role of ADME pharmacogenomics in early clinical trials: perspective of the Industry Pharmacogenomics Working Group (I-PWG).

ABSTRACT: Genetic polymorphisms in metabolizing enzymes and drug transporters have been shown to significantly impact the exposure of drugs having a high dependence on a single mechanism for their absorption, distribution or clearance, such that genotyping can lead to actionable steps in disease treatment. Recently, global regulatory agencies have provided guidance for assessment of pharmacogenomics during early stages of drug development, both in the form of formal guidance and perspectives published in scientific journals. The Industry Pharmacogenomics Working Group (I-PWG), conducted a survey among member companies to assess the practices relating to absorption, distribution, metabolism, excretion pharmacogenomics) during early stages of clinical development, to assess the impact of the recent Regulatory Guidance issued by the US FDA and EMA on Industry practices.

SUBMITTER: Tremaine L

PROVIDER: S-EPMC5558530 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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The role of ADME pharmacogenomics in early clinical trials: perspective of the Industry Pharmacogenomics Working Group (I-PWG).

Tremaine Larry L Brian William W DelMonte Terrye T Francke Stephan S Groenen Peter P Johnson Keith K Li Lei L Pearson Kimberly K Marshall Jean-Claude JC

Pharmacogenomics 20151130 18

Genetic polymorphisms in metabolizing enzymes and drug transporters have been shown to significantly impact the exposure of drugs having a high dependence on a single mechanism for their absorption, distribution or clearance, such that genotyping can lead to actionable steps in disease treatment. Recently, global regulatory agencies have provided guidance for assessment of pharmacogenomics during early stages of drug development, both in the form of formal guidance and perspectives published in ...[more]

PMID: 26616152

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Project description:BackgroundMapping the international landscape of clinical trials may inform global health research governance, but no large-scale data are available. Industry or non-industry sponsorship may have a major influence in this mapping. We aimed to map the global landscape of industry- and non-industry-sponsored clinical trials and its evolution over time.MethodsWe analyzed clinical trials initiated between 2006 and 2013 and registered in the WHO International Clinical Trials Registry Platform (ICTRP). We mapped single-country and international trials by World Bank's income groups and by sponsorship (industry- vs. non- industry), including its evolution over time from 2006 to 2012. We identified clusters of countries that collaborated significantly more than expected in industry- and non-industry-sponsored international trials.Results119,679 clinical trials conducted in 177 countries were analysed. The median number of trials per million inhabitants in high-income countries was 100 times that in low-income countries (116.0 vs. 1.1). Industry sponsors were involved in three times more trials per million inhabitants than non-industry sponsors in high-income countries (75.0 vs. 24.5) and in ten times fewer trials in low- income countries (0.08 vs. 1.08). Among industry- and non-industry-sponsored trials, 30.3% and 3.2% were international, respectively. In the industry-sponsored network of collaboration, Eastern European and South American countries collaborated more than expected; in the non-industry-sponsored network, collaboration among Scandinavian countries was overrepresented. Industry-sponsored international trials became more inter-continental with time between 2006 and 2012 (from 54.8% to 67.3%) as compared with non-industry-sponsored trials (from 42.4% to 37.2%).ConclusionsBased on trials registered in the WHO ICTRP we documented a substantial gap between the globalization of industry- and non-industry-sponsored clinical research. Only 3% of academic trials but 30% of industry trials are international. The latter appeared to be conducted in preferentially selected countries.

Project description:There is an urgent need for strategies to address the US epidemic of prescription opioid, heroin and fentanyl-related overdoses, misuse, addiction, and diversion. Evidence-based treatment such as medications for opioid use disorder (MOUD) are available but lack numbers of providers offering these services to meet the demands. Availability of electronic health record (EHR) systems has greatly increased and led to innovative quality improvement initiatives but this has not yet been optimized to address the opioid epidemic or to treat opioid use disorder (OUD). This report from a clinical decision support (CDS) working group convened by the NIDA Center for the Clinical Trials Network aims to converge electronic technology in the EHR with the urgent need to improve screening, identification, and treatment of OUD in primary care settings through the development of a CDS algorithm that could be implemented as a tool in the EHR. This aim is consistent with federal, state and local government and private sector efforts to improve access and quality of MOUD treatment for OUD, existing clinical quality and HEDIS measures for OUD or drug and alcohol use disorders, and with a recent draft grade B recommendation from the US Preventative Services Task Force (USPSTF) for screening for illicit drug use in adults when appropriate diagnosis, treatment and care services can be offered or referred. Through a face-to-face expert panel meeting and multiple follow-up conference calls, the working group drafted CDS algorithms for clinical care felt to be essential for screening, diagnosis, and management of OUD in primary care. The CDS algorithm was reviewed by addiction specialists and primary care providers and revised based on their input. A clinical decision support tool for OUD screening, assessment, and treatment within primary care systems may help improve healthcare delivery to help address the current epidemic of opioid misuse and overdose that has outpaced the capacity of specialized treatment settings. A semi-structured outline of clinical decision support for OUD was developed to facilitate implementation within the EHR. Further work for adaptation at specific sites and for testing is needed.

Project description:BackgroundHealthcare decisions are ideally based on clinical trial results, published in study registries, as journal articles or summarized in secondary research articles. In this research project, we investigated the impact of academically and commercially sponsored clinical trials on medical practice by measuring the proportion of trials published and cited by systematic reviews and clinical guidelines.MethodsWe examined 691 multicenter, randomized controlled trials that started in 2005 or later and were completed by the end of 2016. To determine whether sponsorship/funding and place of conduct influence a trial's impact, we created four sub-cohorts of investigator initiated trials (IITs) and industry sponsored trials (ISTs): 120 IITs and 171 ISTs with German contribution compared to 200 IITs and 200 ISTs without German contribution. We balanced the groups for study phase and place of conduct. German IITs were funded by the German Research Foundation (DFG), the Federal Ministry of Education and Research (BMBF), or by another non-commercial research organization. All other trials were drawn from the German Clinical Trials Register or ClinicalTrials.gov. We investigated, to what extent study characteristics were associated with publication and impact using multivariable logistic regressions.ResultsFor 80% of the 691 trials, results were published as result articles in a medical journal and/or study registry, 52% were cited by a systematic review, and 26% reached impact in a clinical guideline. Drug trials and larger trials were associated with a higher probability to be published and to have an impact than non-drug trials and smaller trials. Results of IITs were more often published as a journal article while results of ISTs were more often published in study registries. International ISTs less often gained impact by inclusion in systematic reviews or guidelines than IITs.ConclusionAn encouraging high proportion of the clinical trials were published, and a considerable proportion gained impact on clinical practice. However, there is still room for improvement. For publishing study results, study registries have become an alternative or complement to journal articles, especially for ISTs. IITs funded by governmental bodies in Germany reached an impact that is comparable to international IITs and ISTs.

Dataset Information

The role of ADME pharmacogenomics in early clinical trials: perspective of the Industry Pharmacogenomics Working Group (I-PWG).

Publications

The role of ADME pharmacogenomics in early clinical trials: perspective of the Industry Pharmacogenomics Working Group (I-PWG).

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