Drug Assessment Working Group

Overview

The goal of the Drug Assessment Working Group (DAWG) of the Therapeutics Initiative is to clarify the state of scientific evidence regarding effectiveness and safety of drug therapy and to relate that evidence to the care of individual patients. 

The DAWG consists of salaried employees (with expertise in systematic review methodology, clinical pharmacology, and epidemiology), Clinical Fellows in pharmacology, and graduate students from a range of medical disciplines.  The DAWG systematically reviews and, when appropriate, critically appraises research relevant to new and existing drugs.  The purpose of this document is to describe this systematic review process.

The DAWG follows a predefined protocol consisting of a research question, a literature search strategy, and a hierarchy of clinically validated outcome measures.

The research question asks whether the new drug provides a therapeutic advantage over similar drug therapy for a clinical condition ('indication') or versus placebo, in the case of the first drug therapy for a clinical condition. The DAWG relies on its own and external clinical experts both to define clinical conditions and to determine similar drug therapy.
The same DAWG members review all drugs.  That is, the Working Group does not change as drugs change.  And, all of the Working Group are expected to contribute to the design and conclusions of each systematic review, although individual members or groups take the lead for each project. 

None of the DAWG members receives any funding directly or indirectly from the drug industry, nor do they or their families have any stock in any of these companies, except through unassigned mutual funds found in University pensions.

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Drug Assessments

 

The Drug Assessment Working Group (DAWG) is committed to analyze scientific evidence on the effectiveness and safety of drug therapies used in Canada. They systematically review and, when appropriate, critically appraise research relevant to new and existing drugs. Often the goal is to discover whether a new drug provides a therapeutic advantage over existing similar drug therapy for a clinical condition. The Therapeutics Initiative has a dedicated team of researchers that is committed to the highest standards of research.

View Drug Assessments

Assessment Principles

The drug assessment is guided by the following principles:

  1. Therapeutic advantage will be determined by utilizing a hierarchical framework. A hierarchical framework means that an assessment proceeds if, and only if, a series of conditions are met.  If conditions are not met, then the assessment stops at that point.  Therefore, the ordering of the hierarchy is crucial.  The DAWG hierarchy:
    • Type of study: The study must use the strongest possible design: almost always, the double and triple blind, randomized controlled trial.
    • Type of participants: The study must include appropriate participants with an appropriate spectrum of disease from mild to severe; (i.e. a patient population found under normal conditions of clinical care). 
    • Type of intervention: The study must compare the new drug with an established drug with a similar mechanism of action; or with placebo, for drugs with a new mechanism of action.  When the mechanism of action is unknown, comparators must have a similar clinical endpoint.
    • Type of outcome measures: The study must use the most clinically valid outcome measures.  If possible or practical, this should include final outcomes such as serious morbidity and mortality measures.  Intermediate outcomes will be examined, but given less weight because they do not necessarily reflect ultimate morbidity or mortality.
  2. Generally, drug manufacturers have the obligation of demonstrating that their product provides therapeutic advantage over established therapies.

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Search Strategy

A predefined search strategy sets minimum inclusion and exclusion criteria based on major study design features listed above, such as patient selection and assignment, therapies chosen, appropriateness of outcome measures, and the degree of ‘blinding’ as to treatment allocation.

The search strategy only includes full clinical trial reports. Abstracts and poster presentations summarizing clinical trials are insufficient substitutes for full trial reports. Abstracts and poster presentations provide an outline of research design and a summary of major findings.  However, they do not provide sufficient details to determine the validity/quality of the study or its findings. The latter requires analysis of how the trial was conducted and how the results were analysed.

The search includes trials submitted by the manufacturer and electronic data bases: MEDLINE 1966-present database, Current Contents 1996-present database, EMBASE 1988-present, and Cochrane database.  In addition, retrieved clinical trials and some review articles are hand searched for references.

A ‘Search Findings’ section outlines all identified clinical trials and how they are categorized relative to the inclusion and exclusion criteria. Clinical trials and observational studies underway but not yet completed or published are also listed when submitted, but are not considered further in the systematic review unless full trial details are provided by the manufacturer.

Publication requirement

The search strategy includes unpublished, full clinical trial reports submitted by the manufacturer to the Federal and Provincial regulatory and funding agencies, but considered proprietary.  The TI considers this material in its systematic reviews.  However, without publication, the Federal HPB, provincial Drug Benefit Plans, or review groups such as the TI make decisions regarding safety and efficacy, at least in part, on material that is not replicable or refutable.  The TI believes that conducting and completing a clinical trial, but not submitting it for publication and providing full disclosure of the study report is unethical.

A full trial report in a peer reviewed journal is the preferred form of publication. Publication is sometimes delayed by journals. In these instances, copies of the articles as they will appear in publication are included in the drug assessment, along with proof of acceptance by the journal.  

Another source of data are trials submitted for publication to a journal but refused publication. In this case the unpublished trial reports are given the full weight of a published trial, assuming reasonable proof of journal rejection is provided.

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Assessment Process

Clinical trial reports of trials comparing the correct treatments, using the best study design, and the most valid outcome measures are subjected to full critical appraisal. Critical appraisal means assessing the scientific validity of a study report following rigorous predefined criteria, most widely known through the Cochrane Collaboration publications.  Critical appraisal methodology follows the work of Sackett et al,1 and is patterned after Schechter and LeBlanc.2

Each trial is appraised separately by at least two independent DAWG researchers. Discrepancies regarding assessments of  the scientific validity of a clinical trial are resolved through consensus. Each drug assessment is discussed weekly by the full DAWG.

A concluding section of the report summarizes and draws conclusions from the body of available scientific evidence.

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External Review Process

Approximately two-thirds of the DAWG reports are sent for external review.  DAWG reports are not sent for external review if:

  1. the review is of a new formulation of an existing drug where the therapeutic advantage is limited to improved convenience and perhaps compliance with dosing regimen.
  2. the review is an update of a previously reviewed drug sent to reviewers, but no new published RCT evidence is found;
  3. the review is of a ‘me-too’ drug with an established mechanism of action and indication, and no valid published RCT evidence distinguishing the new drug from other members of a well established therapeutic category, such as beta-andrenergic blockers for hypertension or non-steroidal anti-inflammatory medications for osteo-arthritis.

For external review, the draft DAWG report, including the critical appraisal results, plus retrieved publications are sent to at least three experts (clinical or scientific) for assessment and comments.  The reviewers are selected based on their knowledge of systematic review and critical appraisal methodology, their expert clinical or research knowledge of the disease studied,  their ability to respond within a relatively short time-period (i.e. approximately 2 -3 weeks), and their willingness to declare any conflict of interest.  Whenever possible, reviewers without conflicts of interest are chosen. Reviewers are asked, at minimum, to complete a checklist indicating the completeness of the review (any scientific evidence omitted) and whether they agree with the conclusions regarding critical appraisal.

The DAWG takes account of external reviews in the following ways:

1) New Citations are retrieved, and if they meet the inclusion criteria, are added to the review.

2) Internal Validity Issues. Of central concern to the DAWG, are any disagreements between it and external reviewers regarding the internal validity of the appraised clinical trials, particularly regarding key methodological steps such as randomization, the degree of intention to treat analysis, and clinical validity of outcome measures.  These disagreements are discussed within the DAWG, and if the external reviewer’s comments are considered valid, the draft report is revised.  If the DAWG does not consider the methodological issue raised by the external reviewer as valid, the external reviewer is contacted directly for discussion.  If the issue remains un-resolved, both the DAWG and the external reviewer’s opinions are presented to the SIEC for consideration.

3) External Validity Issues.  Interpreting external validity, meaning the extent to which research findings can be extrapolated to different contexts or individuals than those found in clinical trials, is not only difficult, but often the most difficult step in interpreting research findings, especially by individual clinicians.  In part because of the inherent difficulty in establishing external validity, there are often disagreements between the DAWG and external reviewers regarding the interpretation of a therapeutic effect. The DAWG tends to be more conservative, while clinical reviewers are often more liberal in their degree of extrapolation to new individuals or contexts.

The DAWG recognizes that, although external validity issues are extremely important to individual clinicians, these concerns do not affect its mandate to establish the extent and strength of therapeutic effect in scientific evidence.   Therefore, disagreements regarding external validity are not discussed directly with the external reviewers. Instead, both the DAWG and external reviewer’s opinions are presented to the Scientific Information and Education Committee (SIEC) for discussion. 

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Completed DAWG reviews

The reports from the three experts are presented to the SIEC before final conclusions are made.  An attempt is made to reach a consensus. The conclusions are voted on and, if passed by a simple majority, are accepted as the position of the TI regarding the scientific evidence.  Individual members of the SIEC, who are in a conflict of interest position on a particular drug, must declare this and absent themselves from the relevant discussion and vote.

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References

  1. Sackett DL, Haynes RB, Guyatt GH, Tugwell P. Clinical Epidemiology: a basic science for clinical medicine. 2nd re.ed. Boston: Little, Brown and Company, 1991.
  2. Schechter M, and Leblanc FE. Critical appraisal of published literature. In: W. Hanstroidle, O. Spitzer, B. McPeek, D.S. Mulder, and M.F. Mckneally editors, Principles and practice of research: strategies for surgical investigators. New York: Springer-Verlag, 1986:112-17.

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Membership

Dr. Ken Bassett, M.D., Ph.D.

Professor, Departments of Family Practice and Anesthesiology, Pharmacology & Therapeutics, UBC
Faculty Member, Centre for Health Services & Policy Research, UBC
Associate Member, Departments of Ophthalmology, UBC and Health Care and Epidemiology, UBC
Chair, Drug Assessment Working Group, Therapeutics Initiative

Ken Bassett conducts systematic reviews of the efficacy and safety of new and established drugs, as well as pharmaco-epidemiologic studies of serious adverse events associated with prescription drug therapy in British Columbia. His ongoing research interests are in the systematic review of drug therapy and drug funding policy.
No conflict of interest declared | See TI conflict of interest policy

 

Dr. Vijaya Musini, M.D., D.P.H., M.Sc.

Assistant Professor, Dept of Anesthesiology, Pharmacology & Therapeutics, UBC
Manager, Drug Assessment Working Group, Therapeutics Initiative

Vijaya Musini has conducted and supervised over 200 systematic reviews and meta-analyses on prescription drug therapy. She is an Editor of the Cochrane Hypertension Review Group and has been actively involved in teaching Cochrane Collaboration systematic review methodology and critical appraisal skills on evidence based drug therapy to undergraduate, graduate, medical students and residents. Dr. Musini graduated from Mumbai University Medical School in 1982. After completing her rotating internship she joined the Department of Community Medicine in 1984 and graduated with a Diploma in Public Health from Mumbai University Medical School in 1985. She has worked as a Family Practitioner and as a Medical Officer in primary health care centres in Mumbai, India for several years. She also worked as a research assistant in the Departments of Gynaecology and Obstetrics, and Health Care and Epidemiology, Faculty of Medicine, Kuwait University. She immigrated to Canada in 1996 and graduated with a Masters Degree in Pharmacology and Therapeutics from the University of British Columbia in 2000.
No conflict of interest declared | See TI conflict of interest policy

 

Jenny Chen, B.Sc. in Pharmacology

Graduate Student, Dept of Anesthesiology, Pharmacology & Therapeutics, UBC
Research Associate, Drug Assessment Working Group, Therapeutics Initiative

Jenny Chen has obtained a B.Sc in Pharmacology from the University of British Columbia. She has conducted several systematic reviews and meta-analyses on prescription drug therapy and is an author of Cochrane systematic reviews with the Cochrane Hypertension Group.
No conflict of interest declared | See TI conflict of interest policy

 

Dr. Anat Fisher, M.D., M.H.A.

PhD Candidate, Dept of Anesthesiology, Pharmacology & Therapeutics, UBC
Research Associate, Drug Assessment Working Group, Therapeutics Initiative
Anat Fisher obtained her M.D. degree from the Hebrew University of Jerusalem in Israel. She also has a Master of Health Administration from the Tel Aviv University in Israel. She worked as a family practitioner for many years and managed a Hospital Department in a Managed Health Organization. She is an experienced researcher and an expert in data analysis and trend analysis. She has conducted several systematic reviews on safety and efficacy of new drug therapies and is an author of Cochrane systematic reviews.
No conflict of interest declared | See TI conflict of interest policy

 

Patricia Fortin, M.Lib.Sc., M.Sc.(Health Informatics)

Research Consultant, Drug Assessment Working Group, Therapeutics Initiative
Since completing her MSc in Health Informatics in 2005, Patricia Fortin has been involved in several projects in chronic disease management, knowledge translation, and information systems evaluation and adoption. While working as Project Coordinator for Health Technology Assessment for the Provincial Blood Coordinating Office, Patricia worked with the Therapeutics Initiative to complete systematic reviews on blood products to support utilization management. She also has conducted several systematic reviews of drug therapies for the federal Common Drug Review administered by the Canadian Agency for Drugs and Technologies for Health and is an author of Cochrane systematic reviews. Prior to this, Patricia pursued a career as a medical librarian.
No conflict of interest declared | See TI conflict of interest policy

 

Carolyn Green, B.H.Sc. (P.T), P.h.D. (Health Information Sciences)

Research Consultant, Drug Assessment Working Group, Therapeutics Initiative

Carolyn J Green, PhD research interests are organized around providing health care decision makers with research based as well as contextualized research. An active and producer of health technology assessment (HTA) from 1992 she builds on a foundation of research synthesis methodologies, incorporating critical appraisal, meta-analysis, utilization analysis and decision analysis using data from administrative databases, systematic reviews and clinical trials. Doctoral and postdoctoral training has added health informatics and qualitative research perspectives and approaches to her investigations into how knowledge is used in socio-technical systems. To this end she has used institutional ethnography to map health care practice, management and governance systems in relation to regional health boards as well as chronic disease management systems. Carolyn has a BHSc(PT) from McMaster, a MSc from the Department of Health Care and Epidemiology at UBC, a PhD in Health Informatics from the University of Victoria, and has completed a CIHR sponsored postdoctoral fellowship in Knowledge Translation at the University of Alberta. She currently contributes to evidence development in British Columbia through a number of innovative research programs.
No conflict of interest declared | See TI conflict of interest policy

 

Benji HeranDr. Benji Heran, Ph.D.

Research Associate, Drug Assessment Working Group, Therapeutics Initiative
Postdoctoral Research Fellow, Cochrane Heart Group

Balraj (Benji) Heran received a B.Sc. (Hon.) in Physiology at the UBC and joined the TI in 2000. He recently graduated from the Ph.D. program in the Department of Anesthesiology, Pharmacology and Therapeutics, UBC. Under the supervision of Dr. Jim Wright, he conducted two systematic reviews of the dose-related blood pressure lowering efficacy of ACE inhibitors and angiotensin receptor blockers for primary hypertension. He is also a contributing author of a number of systematic reviews and protocols published in the Cochrane Library. From 2003 to 2009 he has served on the editorial team of the Cochrane Collaboration Hypertension Review Group as the Trial Search Co-ordinator, since 2009 has been an Editor with the Cochrane Hypertension Group and a Postdoctoral Research Fellow with the Cochrane Heart Group. He has a keen interest in cardiovascular research.
No conflict of interest declared | See TI conflict of interest policy

 

 

Dr. Fariba Jaffary, M.D., PhD., M.Sc.

Affiliate Associate Professor, Drug Assessment Working Group, Therapeutics Initiative Dept of Anesthesiology, Pharmacology & Therapeutics, UBC
Fariba Jaffary obtained her MD degree from Faculty of Medicine, Isfahan University of medical Sciences(IUMS), Isfahan, Iran in 1989 and graduated from Ph.D degree in Pharmacology in 1995. She had one year fellowship in Clinical Pharmacology at University of Newcastle upon Tyne, UK. She also obtained her MSc. in Medical Education from IUMS in 2003. She has 20 years experience of teaching and research in pharmacology as academic staff in Department of Pharmacology, Faculty of Pharmacy of IUMS. She is an academic member of Skin Disease and leishmaniasis Research Center (SDLRC) and Medical Education Research Center(MERC) at IUMS, also a member of editorial board of Iranian Journal of Medical Education. She joined TI Drug Assessment Working Group in 2004. She has conducted several systematic reviews on efficacy and safety of new drugs.
No conflict of interest declared   

 

Dr Barbara MintzesDr. Barbara Mintzes, B.Sc., Ph.D.

Assistant Professor, Dept of Anesthesiology, Pharmacology & Therapeutics, UBC
Michael Smith Foundation for Health Research Scholar

Barbara Mintzes holds a BA in geography from Simon Fraser University and a PhD in health care and epidemiology from the University of British Columbia. She carries out evaluations of drug safety and effectiveness that provide background information for provincial drug financing decisions. She also works as a clinical reviewer with the Common Drug Review.
The focus of her research is pharmaceutical policy, and her main area of expertise is on the effects of direct-to-consumer advertising of prescription drugs on prescribing and medicine use. She is also involved in research on the influence of regulatory standards for drug promotion on the quality of information provided. She coordinates a global research project on rational use of medicines with Health Action International, a network of consumer, health and development organizations representing public interests in pharmaceutical policy, and is involved in a collaborative World Health Organization project to develop curriculum for pharmacy and medical students on drug promotion and interactions with the industry. She also works with the Pharmaceutical Policy Unit at UBC’s Centre for Health Services and Policy Research, and is a member of the Steering Group of Women and Health Protection.

No conflict of interest declared | See TI conflict of interest policy

 

Dr. Mark Nazer, PhD.

Research Associate, Drug Assessment Working Group, Therapeutics Initiative
Mark Nazer obtained a PhD in Pharmacology & Therapeutics at the University of British Columbia, specializing in cardiovascular pharmacology and physiology, and subsequently publishing in peer-reviewed scientific journals. His systematic reviews have covered a number of medical specialties some of which have included psychiatry and endocrinology. He presently serves on the Board of Directors of a local non-profit health organization.
No conflict of interest declared | See TI conflict of interest policy

 

Dr Marco Perez

 

Dr. Marco Perez, M.D., Ph.D.

PhD (Clin. Pharm.), Dept of Anesthesiology, Pharmacology & Therapeutics, UBC
Researcher, Drug Assessment Working Group, Therapeutics Initiative

Marco Perez obtained his MD degree at the University of Guadalajara, Mexico, in 1991. He completed his specialty in Intensive Care Medicine in 1996. He worked as practicing specialist in an intensive care unit for several years. He obtained his PhD in pharmacology & Therapeutics at the University of British Columbia in 2010, specializing in hypertension and hypertensive emergencies. During his PhD, he conducted two Cochrane systematic Reviews and a randomized controlled trial. He has also been a contributing author of a number of Systematic reviews published in the Cochrane Library and other peer-review medical Journals. Since 2006 he has served on the editorial team on the Cochrane Collaboration- hypertension division. He has also actively involved with the Therapeutics Initiative in the drug assessment-working group, since 2003; and as a clinical reviewer with the Common Drug Review, since 2007. He has evaluated nearly 20 old and new submissions. He is currently holding a postdoctoral research fellow at the Institut de la Sante et Recherche Medicale (INSERM) in the Universit√© de Lyon, France, working in an international- French/Canadian-hypertension research project. 
No conflict of interest declared | See TI conflict of interest policy

 

Dr Tom PerryDr. Thomas Perry jr, M.D., FRCP

Clinical Assistant Professor, Department of Medicine, UBC
Clinical Pharmacologist, General Internist, Vancouver Hospital
Chair, Education Working Group, Therapeutics Initiative

Thomas L. Perry graduated from McGill University Medical School in 1978. After a rotating internship at Dalhousie University, he started a residency in general internal medicine at UBC, broken by 2 years of locum tenens general practice in isolated communities in B.C., Yukon, and Ontario. After completing his specialty residency and achieving Fellowship in the Royal College of Physicians of Canada, he spent one year on a Medical Research Council fellowship studying metabolism of tricyclic antidepressants with Dr. Leif Bertilsson at the Karolinska Institute Department of Clinical Pharmacology in Stockholm, and a further 2 years at UBC's Department of Pharmacology & Therapeutics. Dr. Perry was then elected to the Legislative Assembly of B.C. where he served as Opposition Health Critic from 1989-1991, as Minister for Advanced Education, Training & Technology from 1991-93, and as a government MLA from 1993-96.
Dr. Perry returned to clinical medicine in 1996 and now practices general internal medicine at UBC Hospital and Vancouver General Hospital. He teaches internal medicine in the Department of Medicine Clinical Teaching Unit program at VGH and clinical pharmacology through seminars, lectures and elective student clinical training at UBCH. His outpatient practice focuses on pharmacological treatment of chronic pain and high blood pressure. He has a special interest in the use of videography to teach students and doctors about drugs. He is Chair of the Education Working Group, member of the Drug Assessment Working Group, member of the SIEC and participates frequently in the development of TI Letters.
Dr. Perry's other interests include wilderness canoeing and hiking, environmental conservation, peace and social justice, music, reading, and his family.

Conflict of Interest: Dr. Perry has consulted on a paid basis for Greene & Hoffman (attorneys) of Boston, MA, USA as an expert consultant in clinical pharmacology for a proposed class-action lawsuit against Pfizer Inc. with respect to Neurontin (gabapentin), paid on an hourly rate not contingent upon his opinion. Dr. Perry is a frequent clinical pharmacologic medical legal consultant to the Canadian Medical Protective Association (CMPA) and to the Insurance Corporation of B.C. (ICBC), and occasionally to other defence or plaintiff laywers in medical legal litigation, paid on an hourly rate, where the rate and payment are not contingent upon his opinion. See TI Conflict of Interest Policy

 

Dr Aaron Tejani

Dr. Aaron Tejani, B.Sc(Pharm), Pharm.D, ACPR

Coordinator, Clinical Research and Drug Information Fraser Health Pharmacy Services Researcher, Drug Assessment Working Group, Therapeutics Initiative
Aaron Tejani completed his BSc in pharmaceutical sciences at the University of British Columbia and his Doctor of Pharmacy degree from Creighton University (Omaha, Nebraska). Aaron’s interests include criticall appraisal of the biomedical literature, knowledge translation activities and research, and conducting systematic reviews and meta-analyses of health care interventions. He is also involved in teaching critical appraisal skills to undergraduate and graduate students, as well as health care professionals. He is currently: a member of the Fraser Health Research Ethics Board and the British Columbia Medical Association’s Guidelines and Protocols Advisory Committee, an editor for the Cochrane Hypertension Review Group, a peer reviewer for the Canadian Journal of Emergency Medicine, and a clinical instructor for the Faculty of Pharmaceutical Sciences (University of British Columbia). Within the Therapeutics Initiative, he is a member of the Drug Assessment Working Group, the Education Working Group, and the Scientific Information and Education Committee.
No conflict of interest declared | See TI conflict of interest policy

 

Gavin Wong, B.A. B.Sc.

PhD Candidate, Dept of Anesthesiology, Pharmacology & Therapeutics, UBC
Research Associate, Drug Assessment Working Group, Therapeutics Initiative

Gavin Wong obtained a Bachellor in Economics at the Ohio State University in 2002, a B.Sc in Allied Medical Professions (Respiratory Therapy) at the Ohio State University in 2006 and a RRT in the National Board for Respiratory Care, USA in 2006. He is an Associate Member of the Canadian Society of Respiratory Therapists and an author of Cochrane systematic reviews with the Cochrane Hypertension Group. He has conducted several systematic reviews and meta-analyses on prescription drug therapy.
No conflict of interest declared | See TI conflict of interest policy

 

Dr Jim WrightDr. James M. Wright, M.D., Ph.D., CRCP(C)

Managing Director and Chair, Therapeutics Initiative
Professor, Departments of Anesthesiology, Pharmacology & Therapeutics and Medicine, UBC
Clinical Pharmacologist, Vancouver Hospital
Coordinating Editor, Cochrane Hypertension Review Group

James (Jim) Wright is a Professor in the Departments of Anesthesiology, Pharmacology & Therapeutics and Medicine at the University of BC, Vancouver, Canada. He obtained his MD from the University of Alberta in 1968, his FRCP(C) in Internal Medicine in 1975 and his Ph.D. in Pharmacology from McGill University in 1976. He is a practicing specialist in Internal Medicine and Clinical Pharmacology. He is also Managing Director of the Therapeutics Initiative, Editor-in-Chief of the Therapeutics Letter and Coordinating Editor of the Cochrane Hypertension Review Group. He sits on the Editorial Boards of the following journals: Open Medicine, PLoS One and the Cochrane Library. Dr. Wright's research focuses on issues related to appropriate use of prescription drugs, Clinical Pharmacology, clinical trials, systematic review, meta-analysis and knowledge translation.
No conflict of interest declared | See TI conflict of interest policy