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Rao S, Aggarwal S, Mani S, Balasubramanian A, Veluswami K. Uncovering the Role of Direct Oral Anticoagulants in Stroke Prevention for Atrial Fibrillation: A Review of the Literature. Cureus 2024; 16:e63675. [PMID: 39092362 PMCID: PMC11293488 DOI: 10.7759/cureus.63675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/02/2024] [Indexed: 08/04/2024] Open
Abstract
Atrial fibrillation (AF) is a predominant contributor to morbidity and mortality, and stroke prevention remains the mainstay for the management of AF. The precise mechanism involved in thrombus formation remains unknown. However, factors such as stretch-induced fibrosis, endothelial dysfunction, disordered atrial contractions, and pro-thrombotic states have been postulated for the development of AF. Various risk assessment strategies have been acknowledged for determining the risk of stroke in AF, of which the congestive heart failure, hypertension, age ≥75, diabetes, stroke, vascular disease, age between 65-74, and female sex (CHA2DS2-VASc) score remains the ultimate risk stratification tool. For the longest time, vitamin K antagonists (VKA) were the only oral anticoagulants available but were associated with an increased risk of bleeding. Recently, direct oral anticoagulants (DOACs) were approved and considered more efficient and safer than or as secure as warfarin in stroke prevention and lowering intra-cranial bleeding events. The pharmacodynamics and pharmacokinetics of DOACs were also clarified in this article. This review article compiles current evidence-based data on the role of DOACs, uncovering their underlying mechanisms, and comparing their efficacy with warfarin in stroke prevention in AF.
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Affiliation(s)
- Sudipta Rao
- Internal Medicine, JSS Medical College, Mysore, IND
| | | | - Sweatha Mani
- Internal Medicine, K.A.P. Viswanatham Government Medical College, Tiruchirappalli, IND
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Bai I, Doshi P, Herder M. How to use the regulatory data from Health Canada for secondary analyses on new drugs, biologics and vaccines. BMJ Evid Based Med 2024; 29:187-193. [PMID: 37898504 PMCID: PMC11137451 DOI: 10.1136/bmjebm-2023-112475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/11/2023] [Indexed: 10/30/2023]
Abstract
Incorporating clinical data held by national health product regulatory authorities into secondary analyses such as systematic reviews can help combat publication bias and selective outcome reporting, in turn, supporting more evidence-based decisions regarding the prescribing of drugs, biologics and vaccines. Owing to recent changes in Canadian law, Health Canada has begun to make clinical information-whether it has been previously published or not-publicly available through its 'Public Release of Clinical Information' (PRCI) online database. We provide guidance about how to access and use regulatory data obtained through the PRCI database for the purpose of conducting drug and biologic secondary analyses.
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Affiliation(s)
- Isaac Bai
- Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Peter Doshi
- Department of Practice, Sciences, and Health Outcomes Research, School of Pharmacy, University of Maryland, Baltimore, Maryland, USA
| | - Matthew Herder
- Health Law Institute, Schulich School of Law, Dalhousie University, Halifax, Nova Scotia, Canada
- Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
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3
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Hoffmann JM, Blümle A, Grossmann R, Yau H, Lang B, Bradbury C. Toward a global harmonization of service infrastructure in academic clinical trial units: an international survey. Front Med (Lausanne) 2023; 10:1252352. [PMID: 37901403 PMCID: PMC10602721 DOI: 10.3389/fmed.2023.1252352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 09/25/2023] [Indexed: 10/31/2023] Open
Abstract
Background Clinicians around the world perform clinical research in addition to their high workload. To meet the demands of high quality Investigator Initiated Trials (IITs), Clinical Trial Units (CTUs) (as part of Academic Research Institutions) are implemented worldwide. CTUs increasingly hold a key position in facilitating the international mutual acceptance of clinical research data by promoting clinical research practices and infrastructure according to international standards. Aim In this project, we aimed to identify services that established and internationally operating CTUs - members of the International Clinical Trial Center Network (ICN) - consider most important to ensure the smooth processing of a clinical trial while meeting international standards. We thereby aim to drive international harmonization by providing emerging and growing CTUs with a resource for informed service range set-up. Methods Following the AMEE Guide, we developed a questionnaire, addressing the perceived importance of different CTU services. Survey participants were senior representatives of CTUs and part of the ICN with long-term experience in their field and institution. Results Services concerning quality and coordination of a research project were considered to be most essential, i.e., Quality management, Monitoring and Project management, followed by Regulatory & Legal affairs, Education & Training, and Data management. Operative services for conducting a research project, i.e., Study Nurse with patient contact and Study Nurse without patient contact, were considered to be least important. Conclusion To balance the range of services offered while meeting high international standards of clinical research, emerging CTUs should focus on offering (quality) management services and expertise in regulatory and legal affairs. Additionally, education and training services are required to ensure clinicians are well trained on GCP and legislation. CTUs should evaluate whether the expertise and resources are available to offer operative services.
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Affiliation(s)
- Jean-Marc Hoffmann
- Clinical Trials Center, University of Zurich and University Hospital Zurich, Zurich, Switzerland
| | - Anette Blümle
- Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Regina Grossmann
- Clinical Trials Center, University of Zurich and University Hospital Zurich, Zurich, Switzerland
| | - Henry Yau
- Clinical Trials Centre, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Britta Lang
- Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Cedric Bradbury
- Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
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Laher F, Malahleha M, Ramirez S, Brumskine W, Otwombe K, Moodie Z, Allen M. Data quality in an HIV vaccine efficacy clinical trial in South Africa: through natural disasters and with discipline. BMC Med Res Methodol 2023; 23:147. [PMID: 37355583 PMCID: PMC10290289 DOI: 10.1186/s12874-023-01967-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 06/07/2023] [Indexed: 06/26/2023] Open
Abstract
BACKGROUND To produce quality data that informs valid clinical trial results and withstands regulatory inspection, trial sites should adhere to many complex and dynamic requirements. Understanding non-conformance to requirements informs the emerging field of improvement science. We describe protocol deviations in South Africa's largest HIV vaccine efficacy trial. METHODS We analysed data from the HVTN 702 trial using mixed methods. We obtained descriptive statistics, from protocol deviation case report forms collected from 2016-2022, of deviation by participant, trial site, and time to site awareness. We thematically analysed text narratives of deviation descriptions, corrective and preventive actions, generating categories, codes and themes which emerged from the data. RESULTS For 5407 enrollments, 4074 protocol deviations were reported (75 [95% CI: 73.0-77.6] deviations per 100 enrolments). There was a median of 1 protocol deviation per participant (IQR 1-2). Median time from deviation to site awareness was 31 days (IQR 0-146). The most common category of deviation type was omitted data and/or procedures (69%), and 54% of these omissions were stated to have arisen because of the national lockdown at the beginning of the COVID-19 pandemic. The ratio of protocol deviations to cumulative enrolments was highest in the year 2020 (0.34). Major themes of deviations were: COVID-19 and climate disasters giving rise to deviation trends, subroutines introducing an opportunity for deviation, and document fragmentation (such as requirements dispersed across multiple guidance documents) as an obstacle. Preventive action categories were: no preventive measures; discipline, training and/or awareness; quality review, checking and verifying and changing the process and/or implementation tools. Major themes of preventive actions were that systems-based actions are unusual, with people-based actions dominating, and that root cause analysis was rarely mentioned. CONCLUSIONS In the age of infectious and climate disaster risks, trials may benefit from simple study designs and trial-related documents. To optimise protocol adherence, sponsors and sites should consider ongoing training, and routinely review deviation reports with a view to adjusting processes. These data quality lessons may inform future trial design, training and implementation. TRIAL REGISTRATION HVTN 702 was registered with the South African National Clinical Trials Register (DOH-27-0916-5327) and ClinicalTrials.gov ( NCT02968849 ).
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Affiliation(s)
- Fatima Laher
- Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Diepkloof, P.O. Box 114, Johannesburg, 1864, Soweto, South Africa.
| | - Mookho Malahleha
- Synergy Biomed Research Institute, East London, Eastern Cape, South Africa
| | - Shelly Ramirez
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - William Brumskine
- The Aurum Institute NPC, Johannesburg, Gauteng, South Africa
- Department of Medicine, School of Medicine, Vanderbilt University, Nashville, TN, USA
| | - Kennedy Otwombe
- Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Diepkloof, P.O. Box 114, Johannesburg, 1864, Soweto, South Africa
- School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Zoe Moodie
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Mary Allen
- Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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Cox S, Solbakk JH, Luthardt F, Bernabe RD. Institutional Review Boards and post-approval monitoring (PAM) of human research: content analysis of select university (academic health center) web pages across the USA. Curr Med Res Opin 2023; 39:341-350. [PMID: 36730540 DOI: 10.1080/03007995.2023.2175999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To conduct a content analysis of IRB webpages of select universities (academic health centers) in the USA that describe post IRB- approval monitoring activities. METHOD This was a qualitative study. Thematic analysis was the method to review the webpage content of selected academic health centers (AHC) within the USA. RESULTS Some US academic health "centers" IRB administrative or research compliance offices conduct post- approval monitoring (PAM) of human subjects' research including clinical trials. The goals of this PAM programmes are to (a) ensure compliance to approved protocols, (b) preserve research integrity, (c) manage institutional risks, d) provide advisory/educational support to researchers, (e) recommend corrective actions for identified issues, and most importantly, (f) to protect the safety, rights, and well-being of research participants. Although not a requirement by law, the PAM program has legislative support in the US Code of Federal Regulations as part of the US Office for Human Research Protection's (OHRP) Federal Wide Assurance (FWA). This is especially for institutions that conduct studies funded by the Federal government. PAM on-site checks reveal various incidents of protocol deviations and violations. This includes issues with recruitment processes, informed consent discrepancies, and incidents of non-compliance. When a study protocol is identified as non-compliant, the principal investigator works with the PAM monitor to develop a corrective action plan that would allow the study to become compliant and avoid sanctions from the IRB or the regulatory authority. CONCLUSIONS REC/IRB post-approval monitoring of clinical trials is a valuable mechanism of protection for research participants while giving educational and quality assurance support to researchers. The program enables early detection and resolution of non-compliance to approved protocols. The impact of the program in the USA requires further exploration.
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Affiliation(s)
- Shereen Cox
- Centre for Medical Ethics, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Jan Helge Solbakk
- Centre for Medical Ethics, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Frederick Luthardt
- OHSR Compliance Monitoring Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Rosemarie Dlc Bernabe
- Centre for Medical Ethics, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
- The Faculty of Health and Social Sciences, University of Southeastern Norway, Kongsberg, Norway
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Ann Costa Clemens S, Keiko Sekine A, Tovar-Moll F, Clemens R. COVID-19 Site Readiness Initiative: Building Clinical Trial Capacity for Vaccine Efficacy Trials in Latin America in Response to the Pandemic. Vaccine X 2022; 12:100238. [PMCID: PMC9647642 DOI: 10.1016/j.jvacx.2022.100238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 09/05/2022] [Accepted: 11/07/2022] [Indexed: 11/10/2022] Open
Abstract
According to the World Health
Organization, the American region has the highest coronavirus
disease-2019 (COVID-19) cases and deaths since the start of the pandemic.
This humanitarian tragedy presented the possibility of generating
efficacy data from COVID-19 vaccine trials. The race to develop
successful vaccines imposed a high demand for trained healthcare
personnel and clinical sites where large scale randomized clinical trials
could be conducted. This site readiness initiative, funded by the Bill
and Melinda Gates Foundation (BMGF), was carried out to rapidly build
site capacity for running COVID-19 vaccine trials in Latin
America. Twenty-two sites across 7 countries
were selected and received funding. Site selection was based on defined
feasibility criteria which deemed these sites as suitable for running
vaccine efficacy trials. Criteria for selection included investigator and
core permanent staff experience, public health measures in place for
COVID-19, import/export requirements for study drug and biological
specimens, a clear and accelerated ethical and regulatory approval
process for COVID-19 trials. Training was tailored and delivered
according to the experience level of the investigator and site staff, and
included GCP training, standard operating procedures (SOP) fundamentals,
conducting vaccine trials, COVID-19 pathophysiology, and vaccine trials
lessons learned. Most of the grant funds were utilized for space
expansion and renovation (46%) followed by purchase of equipment (36%);
the remaining 18% was spent on human resources. By the end of this site
readiness initiative project, which took approximately 4 months, 21 of 22
(95%) sites had agreements in place or were in discussions with sponsors
to conduct large scale COVID-19 vaccine trials.
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Steiner T, Dichgans M, Norrving B, Aamodt AH, Berge E, Christensen H, Fuentes B, Khatri P, Korompoki E, Martí-Fabregas J, Quinn T, Toni D, Zedde M, Sacco S, Turc G. European Stroke Organisation (ESO) standard operating procedure for the preparation and publishing of guidelines. Eur Stroke J 2021; 6:CXXII-CXXXIV. [PMID: 34746429 DOI: 10.1177/23969873211024143] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 05/10/2021] [Indexed: 11/17/2022] Open
Abstract
The first European Stroke Organization (ESO) standard operating procedure (SOP) published in 2015 aimed at the implementation the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to provide evidence-based guidelines for stroke management. This second ESO-SOP is aiming at further increase of the practicability of ESO guidelines and its technical implications. Authors comprised of the members of the ESO guideline Board and ESO Executive Committee. The final document was agreed on by several internal reviews. The second SOP comprises of the following aspects: rational for the SOP, the introduction of expert consensus statements, types of guideline documents, structures involved and detailed description of the guideline preparation process, handling of financial and intellectual conflicts of interest (CoI), involvement of ESO members in the guideline process, review process, authorship and publication policy, updating of guidelines, cooperation with other societies, and dealing with falsified data. This second SOP supersedes the first SOP published in 2015.
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Affiliation(s)
- T Steiner
- Department of Neurology, Klinikum Frankfurt Höchst GmbH, Frankfurt am Main, Germany.,Department of Neurology Hospital, Heidelberg University, Heidelberg, Germany
| | - M Dichgans
- Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.,German Center for Neurodegenerative Diseases (DZNE, Munich), Munich, Germany.,Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
| | - B Norrving
- Department of Clinical Sciences Lund University Hospital and Lund University Departmnet of Neurology, Skane University Hospital, Lund, Sweden
| | - A H Aamodt
- Department of Neurology, Oslo University Hospital, Oslo, Norway
| | - E Berge
- Department of Internal Medicine, Oslo University Hospital, Oslo, Norway
| | - H Christensen
- Department of Neurology, Bispebjerg Hospital, University of Copenhagen, Kobenhavn, Denmark
| | - B Fuentes
- Department of Neurology, Hospital Universitario La Paz, Madrid, Spain
| | - P Khatri
- Department of Neurology, University of Cincinnati Medical Center, Cincinnati, OH, USA
| | - E Korompoki
- Division of Brain Science, Imperial College London, London, UK.,Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece
| | | | - T Quinn
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - D Toni
- Departments of Neurological Sciences and Emergency, Unità di Trattamento Neurovascolare, University of Rome La Sapienza, Rome, Italy
| | - M Zedde
- Neurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale - IRCCS, di Reggio Emilia, Reggio Emilia, Italy
| | - S Sacco
- Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, L'Aquila, Italy
| | - G Turc
- Neurology Department, GHU Paris Psychiatrie et Neurosciences, Université de Paris, Paris, France
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9
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White CM, White LR. Preventing a New Tuskegee: Food and Drug Administration Oversight of Overseas Research Must Match That in the United States. J Clin Pharmacol 2021; 62:434-437. [PMID: 34592028 DOI: 10.1002/jcph.1976] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 09/27/2021] [Indexed: 11/09/2022]
Affiliation(s)
- C Michael White
- University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.,Hartford Hospital, Hartford, Connecticut, USA
| | - Lyla R White
- University of Connecticut School of Pharmacy, Storrs, Connecticut, USA
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10
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Abi-Jaoude E, Lexchin J. Health Canada: optimizing transparency and its impact for patients. CMAJ 2021; 193:E1503. [PMID: 34580145 PMCID: PMC8486473 DOI: 10.1503/cmaj.80084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Affiliation(s)
- Elia Abi-Jaoude
- Psychiatrist, assistant professor, University of Toronto, Toronto, Ont
| | - Joel Lexchin
- Emergency physician, University Health Network, Toronto, Ont
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11
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Boesen K, Juhl Jørgensen K, Gøtzsche PC. The US Food and Drug Administration's authorisation of Purdue's controlled-release methylphenidate for adult ADHD: comments on the regulatory practice. J R Soc Med 2021; 114:377-380. [PMID: 33759627 PMCID: PMC8361378 DOI: 10.1177/0141076821994535] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Kim Boesen
- Nordic Cochrane Centre, Rigshospitalet Dept. 7112, Copenhagen, Denmark
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12
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Fanelli D, Wong J, Moher D. What difference might retractions make? An estimate of the potential epistemic cost of retractions on meta-analyses. Account Res 2021; 29:442-459. [PMID: 34196235 DOI: 10.1080/08989621.2021.1947810] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The extent to which a retraction might require revising previous scientific estimates and beliefs - which we define as the epistemic cost - is unknown. We collected a sample of 229 meta-analyses published between 2013 and 2016 that had cited a retracted study, assessed whether this study was included in the meta-analytic estimate and, if so, re-calculated the summary effect size without it. The majority (68% of N = 229) of retractions had occurred at least one year prior to the publication of the citing meta-analysis. In 53% of these avoidable citations, the retracted study was cited as a candidate for inclusion, and only in 34% of these meta-analyses (13% of total) the study was explicitly excluded because it had been retracted. Meta-analyses that included retracted studies were published in journals with significantly lower impact factor. Summary estimates without the retracted study were lower than the original if the retraction was due to issues with data or results and higher otherwise, but the effect was small. We conclude that meta-analyses have a problematically high probability of citing retracted articles and of including them in their pooled summaries, but the overall epistemic cost is contained.
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Affiliation(s)
- Daniele Fanelli
- Department of Methodology, London School of Economics and Political Science, London, UK
| | | | - David Moher
- Centre for Journalology, Clinical Epidemiology Program, Ottawa Hospital Research Institute, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada
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13
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Cox S, Solbakk JH, Bernabe RDLC. The role of research ethics committees after the approval of clinical trial protocols in the EU and the USA: a descriptive content analysis of international and regional normative documents. Curr Med Res Opin 2021; 37:1061-1069. [PMID: 33734933 DOI: 10.1080/03007995.2021.1905621] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
AIM To conduct a descriptive content analysis of normative documents on the role of research ethics committees (RECs) after the approval of clinical trial protocols. The question to be addressed is whether and to what extent normative documents support a monitoring role for RECs in the United States and the European Union. DESIGN A qualitative content analysis of 19 normative documents on clinical research as outlined by the International Compilation of Human Research Standards 2020 edition and other related documents for the EU and USA. RESULTS After the approval of research protocols, RECs' general role is to receive reports from researchers on the trials' progress. Additionally, RECs receive notifications of protocol amendments, deviations and, to a lesser extent, violations, which is the remit of the regulatory/competent authorities. RECs are expected to issue opinions on clinical trials' progress and give supplemental opinions/approval or withdraw/suspend/terminate previous favorable opinions on adverse events or safety concerns that may arise. RECs are to receive an end of the trial report. CONCLUSION The role of RECs post approval of protocols is to protect human participants through activities such as continuing review of: (a) progress reports, (b) notifications of significant protocol amendments, (c) adverse events, (d) protocol deviations, and (e) protocol violations. Although some international guidelines such as the Declaration of Helsinki emphasize the right to monitor, RECs' predominant activity is document review. In the USA, RECs are authorized to issue approvals and terminate/suspend previously issued approvals. However, in the EU, the approach is to relegate to member states to decide the extent of legislative power they wish to give to the RECs. The REC's opinion on the end of trial report is identified as an area for further exploration.
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Affiliation(s)
- Shereen Cox
- Center for Medical Ethics, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Jan Helge Solbakk
- Center for Medical Ethics, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Rosemarie D L C Bernabe
- Center for Medical Ethics, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
- Faculty of Health and Social Sciences, University of South-Eastern Norway, Kongsberg, Norway
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14
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Ignoring instead of chasing after coagulation factor VII during warfarin management: an interrupted time series study. Blood 2021; 137:2745-2755. [PMID: 33512454 DOI: 10.1182/blood.2020008698] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 12/20/2020] [Indexed: 12/11/2022] Open
Abstract
During warfarin management, variability in prothrombin time-based international normalized ratio (PT-INR) is caused, in part, by clinically inconsequential fluctuations in factor VII (FVII). The new factor II and X (Fiix)-prothrombin time (Fiix-PT) and Fiix-normalized ratio (Fiix-NR), unlike PT-INR, are only affected by reduced FII and FX. We assessed the incidence of thromboembolism (TE) and major bleeding (MB) in all 2667 patients on maintenance-phase warfarin managed at our anticoagulation management service during 30 months; 12 months prior to and 18 months after replacing PT-INR monitoring with Fiix-NR monitoring. Months 13 to 18 were predefined as transitional months. Using 2-segmented regression, a breakpoint in the monthly incidence of TE became evident 6 months after test replacement, that was followed by a 56% reduction in incidence (from 2.82% to 1.23% per patient-year; P = .019). Three-segmented regression did not find any significant trend in TE incidence (slope, +0.03) prior to test replacement; however, during months 13 to 18 and 19 to 30, the incidence of TE decreased gradually (slope, -0.12; R2 = 0.20; P = .007). The incidence of MB (2.79% per patient-year) did not differ. Incidence comparison during the 12-month Fiix and PT periods confirmed a statistically significant reduction (55-62%) in TE. Fiix monitoring reduced testing, dose adjustments, and normalized ratio variability and prolonged testing intervals and time in range. We conclude that ignoring FVII during Fiix-NR monitoring in real-world practice stabilizes the anticoagulant effect of warfarin and associates with a major reduction in TEs without increasing bleeding.
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15
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Radecki RP, Spiegel RS. Bridging Oceans and Thrombolysis: April 2021 Annals of Emergency Medicine Journal Club. Ann Emerg Med 2021; 77:464-465. [PMID: 33766279 DOI: 10.1016/j.annemergmed.2021.02.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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16
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Garmendia CA. Coding Errors in Study of Meta-analyses With Falsified Data in the Results. JAMA Intern Med 2021; 181:408-409. [PMID: 33226433 DOI: 10.1001/jamainternmed.2020.7164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Craig A Garmendia
- Office of Bioresearch Monitoring Operations, Office of Regulatory Affairs Food and Drug Administration, Miami, Florida
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17
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Grey A, Avenell A, Gamble G, Bolland M. Assessing and Raising Concerns About Duplicate Publication, Authorship Transgressions and Data Errors in a Body of Preclinical Research. SCIENCE AND ENGINEERING ETHICS 2020; 26:2069-2096. [PMID: 31673984 DOI: 10.1007/s11948-019-00152-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 10/24/2019] [Indexed: 05/03/2023]
Abstract
Authorship transgressions, duplicate data reporting and reporting/data errors compromise the integrity of biomedical publications. Using a standardized template, we raised concerns with journals about each of these characteristics in 33 pairs of publications originating from 15 preclinical (animal) trials reported by a group of researchers. The outcomes of interest were journal responses, including time to acknowledgement of concerns, time to decision, content of decision letter, and disposition of publications at 1 year. Authorship transgressions affected 27/36 (75%) publications. The median proportion of duplicate data within pairs of publications was 45% (interquartile range 29-57). Data/reporting discrepancies [median 3 (1-5)] were present in 28/33 (85%) pairs. Journals acknowledged receipt of concerns for 53% and 94% of publications by 1 month and 9 months, respectively. After 1 year, journals had communicated decisions for 16/36 (44%) publications. None of the decision letters specifically addressed each of the concerns raised. Decisions were no action, correction and retraction for 9, 3 and 4 publications, respectively: the amounts of duplicate data reporting and data/reporting discrepancies were similar irrespective of journal decision. Authorship transgressions affected 6/9 (67%) publications for which no action was decided. Journal responses to concerns about duplicate publication, authorship transgressions, and data/reporting discrepancies were slow, opaque and inconsistent.
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Affiliation(s)
- Andrew Grey
- Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand.
| | - Alison Avenell
- Health Services Research Unit, University of Aberdeen, Aberdeen, UK
| | - Greg Gamble
- Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand
| | - Mark Bolland
- Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand
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18
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Dal-Ré R, Kesselheim AS, Bourgeois FT. Increasing Access to FDA Inspection Reports on Irregularities and Misconduct in Clinical Trials. JAMA 2020; 323:1903-1904. [PMID: 32324205 DOI: 10.1001/jama.2020.1631] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Rafael Dal-Ré
- Epidemiology Unit, Health Research Institute─Fundación Jimenez Díaz, University Hospital, Universidad Autónoma de Madrid, Madrid, Spain
| | - Aaron S Kesselheim
- Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Florence T Bourgeois
- Computational Health Informatics Program (CHIP), Boston Children's Hospital, Boston, Massachusetts
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
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19
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Porsdam Mann S, Savulescu J, Ravaud P, Benchoufi M. Blockchain, consent and prosent for medical research. JOURNAL OF MEDICAL ETHICS 2020; 47:medethics-2019-105963. [PMID: 32366703 PMCID: PMC8053330 DOI: 10.1136/medethics-2019-105963] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Revised: 03/20/2020] [Accepted: 03/27/2020] [Indexed: 05/31/2023]
Abstract
Recent advances in medical and information technologies, the availability of new types of medical data, the requirement of increasing numbers of study participants, as well as difficulties in recruitment and retention, all present serious problems for traditional models of specific and informed consent to medical research. However, these advances also enable novel ways to securely share and analyse data. This paper introduces one of these advances-blockchain technologies-and argues that they can be used to share medical data in a secure and auditable fashion. In addition, some aspects of consent and data collection, as well as data access management and analysis, can be automated using blockchain-based smart contracts. This paper demonstrates how blockchain technologies can be used to further all three of the bioethical principles underlying consent requirements: the autonomy of patients, by giving them much greater control over their data; beneficence, by greatly facilitating medical research efficiency and by reducing biases and opportunities for errors; and justice, by enabling patients with rare or under-researched conditions to pseudonymously aggregate their data for analysis. Finally, we coin and describe the novel concept of prosent, by which we mean the blockchain-enabled ability of all stakeholders in the research process to pseudonymously and proactively consent to data release or exchange under specific conditions, such as trial completion.
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Affiliation(s)
- Sebastian Porsdam Mann
- Department of Communication, University of Copenhagen Faculty of Humanities, København, Denmark
- Oxford Uehiro Centre for Practical Ethics, University of Oxford, Oxford, UK
| | - Julian Savulescu
- Faculty of Philosophy, Oxford Uehiro Centre for Practical Ethics, Oxford, UK
| | - Philippe Ravaud
- Mailman School of Public Health, Columbia University, New York, New York, USA
- Clinical Epidemiology, Université Paris Descartes Faculté de Médecine, Paris, Île-de-France, France
| | - Mehdi Benchoufi
- Clinical Epidemiology, Universite Paris Descartes Faculté de Médecine, Paris, Île-de-France, France
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20
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Bozorghadad S, Newton IG, Perez AW, Makary MS, Keller EJ. Research Ethics in IR: The Intersection Between Care and Progress. J Vasc Interv Radiol 2020; 31:846-848. [PMID: 32359529 DOI: 10.1016/j.jvir.2020.02.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 02/08/2020] [Accepted: 02/14/2020] [Indexed: 11/15/2022] Open
Affiliation(s)
| | - Isabel G Newton
- Department of Radiology, Division of Vascular and Interventional Radiology, University of California San Diego, San Diego, California
| | - Andrew W Perez
- Department of Radiology, Division of Vascular and Interventional Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Mina S Makary
- Department of Radiology, Division of Vascular and Interventional Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Eric J Keller
- Department of Radiology, Division of Vascular and Interventional Radiology, Stanford University, 300 Pasteur Drive, H3630, Stanford, CA 94305.
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21
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Dankar FK, Gergely M, Malin B, Badji R, Dankar SK, Shuaib K. Dynamic-informed consent: A potential solution for ethical dilemmas in population sequencing initiatives. Comput Struct Biotechnol J 2020; 18:913-921. [PMID: 32346464 PMCID: PMC7182686 DOI: 10.1016/j.csbj.2020.03.027] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 03/29/2020] [Accepted: 03/30/2020] [Indexed: 01/13/2023] Open
Abstract
While the majority of population-level genome sequencing initiatives claim to follow the principles of informed consent, the requirements for informed consent have not been-well defined in this context. In fact, the implementation of informed consent differs greatly across these initiatives - spanning broad consent, blanket consent, and tiered consent among others. As such, this calls for an investigation into the requirements for consent to be "informed" in the context of population genomics. One particular strategy that claims to be fully informed and to continuously engage participants is called "dynamic consent". Dynamic consent is based on a personalised communication platform that aims to facilitate the consent process. It is oriented to support continuous two-way communication between researchers and participants. In this paper, we analyze the requirements of informed consent in the context of population genomics, review various current implementations of dynamic consent, assess whether they fulfill the requirement of informed consent, and, in turn, enable participants to make autonomous and informed choices on whether or not to participate in research projects.
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Affiliation(s)
- Fida K. Dankar
- College of Information Technology, UAEU, Al-Ain, United Arab Emirates
| | - Marton Gergely
- College of Information Technology, UAEU, Al-Ain, United Arab Emirates
| | - Bradley Malin
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States
- Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN, United States
| | | | | | - Khaled Shuaib
- College of Information Technology, UAEU, Al-Ain, United Arab Emirates
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22
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White CM. Current System of Overseeing Drug Trials in Developing Countries by the FDA Is Dangerous. Ann Pharmacother 2020; 54:928-932. [PMID: 32037852 DOI: 10.1177/1060028020906484] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Clinical research used to substantiate Food and Drug Administration (FDA) drug approval is increasingly being conducted overseas. One of the enticements to move overseas is unequal oversight by the FDA, and these differences can result in poor quality research and human subject risk. Downstream, patients, clinicians, and payers of health care can be harmed by inaccuracies in the new drug approval process. The need of the hour is to bridge the gap in the standards by ensuring that the investigators in the developing countries adhere to the same quality standards as the domestic investigators.
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Affiliation(s)
- C Michael White
- University of Connecticut School of Pharmacy, Storrs, CT, and Hartford Hospital, USA
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23
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Jame S, Barnes G. Stroke and thromboembolism prevention in atrial fibrillation. Heart 2019; 106:10-17. [PMID: 31533990 DOI: 10.1136/heartjnl-2019-314898] [Citation(s) in RCA: 83] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 08/15/2019] [Accepted: 08/16/2019] [Indexed: 12/11/2022] Open
Abstract
Prevention of stroke and systemic thromboembolism remains the cornerstone for management of atrial fibrillation (AF) and flutter. Multiple risk assessment models for stroke and systemic thromboembolism are currently available. The score, with its known limitations, remains as the recommended risk stratification tool in most major guidelines. Once at-risk patients are identified, vitamin K antagonists (VKAs) and, more recently, direct oral anticoagulants (DOACs) are the primary medical therapy for stroke prevention. In those with contraindication for long-term anticoagulation, left atrial appendage occluding devices are developing as a possible alternative therapy. Some controversy exists regarding anticoagulation management for cardioversion of acute AF (<48 hours); however, systemic anticoagulation precardioversion and postcardioversion is recommended for those with longer duration of AF. Anticoagulation management peri-AF ablation is also evolving. Uninterrupted VKA and DOAC therapy has been shown to reduce perioperative thromboembolic risk with no significant escalation in major bleeding. Currently, under investigation is a minimally interrupted approach to anticoagulation with DOACs periablation. Questions remain, especially regarding the delivery of anticoagulation care and integration of wearable rhythm monitors in AF management.
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Affiliation(s)
- Sina Jame
- Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA
| | - Geoffrey Barnes
- Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, USA
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24
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Behdarvand B, Karanges EA, Bero L. Pharmaceutical industry funding of events for healthcare professionals on non-vitamin K oral anticoagulants in Australia: an observational study. BMJ Open 2019; 9:e030253. [PMID: 31434780 PMCID: PMC6707659 DOI: 10.1136/bmjopen-2019-030253] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVES To describe the nature, frequency and content of non-vitamin K oral anticoagulant (NOAC)-related events for healthcare professionals sponsored by the manufacturers of the NOACs in Australia. A secondary objective is to compare these data to the rate of dispensing of the NOACs in Australia. DESIGN AND SETTING This cross-sectional study examined consolidated data from publicly available Australian pharmaceutical industry transparency reports from October 2011 to September 2015 on NOAC-related educational events. Data from April 2011 to June 2016 on NOAC dispensing, subsidised under Australia's Pharmaceutical Benefits Scheme (PBS), were obtained from the Department of Health and the Department of Human Services. MAIN OUTCOME MEASURES Characteristics of NOAC-related educational events including costs (in Australian dollars, $A), numbers of events, information on healthcare professional attendees and content of events; and NOAC dispensing rates. RESULTS During the study period, there were 2797 NOAC-related events, costing manufacturers a total of $A10 578 745. Total expenditure for meals and beverages at all events was $A4 238 962. Events were predominantly attended by general practitioners (42%, 1174/2797), cardiologists (35%, 977/2797) and haematologists (23%, 635/2797). About 48% (1347/2797) of events were held in non-clinical settings, mainly restaurants, bars and cafes. Around 55% (1551/2797) of events consisted of either conferences, meetings or seminars. The analysis of the content presented at two events detected promotion of NOACs for unapproved indications, an emphasis on a favourable benefit/harm profile, and that all speakers had close ties with the manufacturers of the NOACs. Following PBS listings relevant to each NOAC, the numbers of events related to that NOAC and the prescribing of that NOAC increased. CONCLUSIONS Our findings suggest that the substantial investment in NOAC-related events made by four pharmaceutical companies had a promotional purpose. Healthcare professionals should seek independent information on newly subsidised medicines from, for example, government agencies or drug bulletins.
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Affiliation(s)
- Behrad Behdarvand
- Charles Perkins Centre and School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Emily A Karanges
- Charles Perkins Centre and School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Lisa Bero
- Charles Perkins Centre and School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
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25
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Publication. CLIN NURSE SPEC 2019. [DOI: 10.1097/nur.0000000000000455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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26
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Garmendia CA, Madhivanan P. Correcting Meta-analyses and Reviews Affected by Retracted Research-Reply. JAMA Intern Med 2019; 179:1006. [PMID: 31260023 DOI: 10.1001/jamainternmed.2019.1870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Craig A Garmendia
- US Food and Drug Administration, Miami, Florida.,Florida International University, Miami, Florida
| | - Purnima Madhivanan
- Department of Health Promotion Sciences, Mel & Enid Zuckerman College of Public Health, University of Arizona
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27
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Garmendia CA, Nassar Gorra L, Rodriguez AL, Trepka MJ, Veledar E, Madhivanan P. Evaluation of the Inclusion of Studies Identified by the FDA as Having Falsified Data in the Results of Meta-analyses: The Example of the Apixaban Trials. JAMA Intern Med 2019; 179:582-584. [PMID: 30830216 PMCID: PMC6450302 DOI: 10.1001/jamainternmed.2018.7661] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
This study evaluates the inclusion of studies identified by the FDA as having falsified data in the results of meta-analyses.
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Affiliation(s)
- Craig A Garmendia
- Office of Bioresearch Monitoring Operations, Office of Regulatory Affairs, US Food and Drug Administration, Miami, Florida
| | - Liliana Nassar Gorra
- Department of Epidemiology, Robert Stempel College of Public Health and Social Work, Florida International University, Miami
| | - Ana Lucia Rodriguez
- Department of Psychology, School of Integrated Science and Humanity, Florida International University, Miami
| | - Mary Jo Trepka
- Department of Epidemiology, Robert Stempel College of Public Health and Social Work, Florida International University, Miami
| | - Emir Veledar
- Department of Biostatistics, Robert Stempel College of Public Health and Social Work, Florida International University, Miami
| | - Purnima Madhivanan
- Department of Epidemiology, Robert Stempel College of Public Health and Social Work, Florida International University, Miami
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28
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Plottel CS, Mannon L, More FG, Katz SD, Hochman JS. Design, implementation, and evaluation of PINDAR, a novel short program on GCP for academic medical center principal investigators conducting human subject research. J Clin Transl Sci 2018; 2:343-349. [PMID: 31404275 PMCID: PMC6676438 DOI: 10.1017/cts.2019.5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 01/23/2019] [Accepted: 01/26/2019] [Indexed: 11/26/2022] Open
Abstract
The Principal INvestigator Development and Resources (PINDAR) program was developed at the NYU-H+H Clinical and Translational Science Award (CTSA) hub in response to a perceived need for focused good clinical practice (GCP) training designed specifically for principal investigators (PIs) performing human subject research. PINDAR is a novel 6-hour, instructor lead, participatory, in-person course for PIs developed de novo, piloted, and implemented. One hundred and seventeen faculty PIs participated in PINDAR from November 2016 through September 2018. All obtained mutual recognition for ICH E6 GCP training from TransCelerate Biopharma. PINDAR was well received by participant PIs, and feedback surveys have revealed a high degree of satisfaction with the program. Other CTSA hubs and research-intensive health systems should consider adopting a similar course focused on GCP for PIs.
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Affiliation(s)
- Claudia S. Plottel
- Department of Medicine, New York University School of Medicine, New York, New York, USA
- NYU-H+H Clinical Translational Science Institute, New York, New York, USA
| | - Lois Mannon
- Office of Science and Research (OSR), NYU Langone Health, New York, New York, USA
| | - Frederick G. More
- Office of Science and Research (OSR), NYU Langone Health, New York, New York, USA
- NYU College of Dentistry, New York, New York, USA
| | - Stuart D. Katz
- Department of Medicine, New York University School of Medicine, New York, New York, USA
- NYU-H+H Clinical Translational Science Institute, New York, New York, USA
| | - Judith S. Hochman
- Department of Medicine, New York University School of Medicine, New York, New York, USA
- NYU-H+H Clinical Translational Science Institute, New York, New York, USA
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29
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Godecharle S, Nemery B, Dierickx K. Differing Perceptions Concerning Research Integrity Between Universities and Industry: A Qualitative Study. SCIENCE AND ENGINEERING ETHICS 2018; 24:1421-1436. [PMID: 28913604 DOI: 10.1007/s11948-017-9965-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 08/22/2017] [Indexed: 06/07/2023]
Abstract
Despite the ever increasing collaboration between industry and universities, the previous empirical studies on research integrity and misconduct excluded participants of biomedical industry. Hence, there is a lack of empirical data on how research managers and biomedical researchers active in industry perceive the issues of research integrity and misconduct, and whether or not their perspectives differ from those of researchers and research managers active in universities. If various standards concerning research integrity and misconduct are upheld between industry and universities, this might undermine research collaborations. Therefore we performed a qualitative study by conducting 22 semi-structured interviews in order to investigate and compare the perspectives and attitudes concerning the issues of research integrity and misconduct of research managers and biomedical researchers active in industry and universities. Our study showed clear discrepancies between both groups. Diverse strategies in order to manage research misconduct and to stimulate research integrity were observed. Different definitions of research misconduct were given, indicating that similar actions are judged heterogeneously. There were also differences at an individual level, whether the interviewees were active in industry or universities. Overall, the management of research integrity proves to be a difficult exercise, due to many diverse perspectives on several essential elements connected to research integrity and misconduct. A management policy that is not in line with the vision of the biomedical researchers and research managers is at risk of being inefficient.
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Affiliation(s)
- Simon Godecharle
- Department of Public Health and Primary Care, Centre for Biomedical Ethics and Law, University of Leuven, Kapucijnenvoer 35, Box 7001, 3000, Louvain, Belgium.
| | - Benoit Nemery
- Department of Public Health and Primary Care, Centre for Environment and Health, University of Leuven, 3000, Louvain, Belgium
| | - Kris Dierickx
- Department of Public Health and Primary Care, Centre for Biomedical Ethics and Law, University of Leuven, Kapucijnenvoer 35, Box 7001, 3000, Louvain, Belgium
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Abstract
Research ethics provide important and necessary standards related to the conduct and dissemination of research. To better understand the current state of research ethics discourse in social work, a systematic literature search was undertaken and numbers of publications per year were compared between STEM, social science, and social work disciplines. While many professions have embraced the need for discipline-specific research ethics subfield development, social work has remained absent. Low publication numbers, compared to other disciplines, were noted for the years (2006-2016) included in the study. Social work published 16 (1%) of the 1409 articles included in the study, contributing 3 (>1%) for each of the disciplines highest producing years (2011 and 2013). Comparatively, psychology produced 75 (5%) articles, psychiatry produced 64 (5%) articles, and nursing added 50 (4%) articles. The STEM disciplines contributed 956 (68%) articles between 2006 and 2016, while social science produced 453 (32%) articles. Examination of the results is provided in an extended discussion of several misconceptions about research ethics that may be found in the social work profession. Implications and future directions are provided, focusing on the need for increased engagement, education, research, and support for a new subfield of social work research ethics.
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Affiliation(s)
- Aidan Ferguson
- a College of Social Work , Florida State University , Tallahassee , USA
| | - James J Clark
- a College of Social Work , Florida State University , Tallahassee , USA
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31
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Borioli GS, Couturier J. How blockchain technology can improve the outcomes of clinical trials. ACTA ACUST UNITED AC 2018. [DOI: 10.12968/bjhc.2018.24.3.156] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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32
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Li G, Kamel M, Jin Y, Xu MK, Mbuagbaw L, Samaan Z, Levine MA, Thabane L. Exploring the characteristics, global distribution and reasons for retraction of published articles involving human research participants: a literature survey. J Multidiscip Healthc 2018; 11:39-47. [PMID: 29403283 PMCID: PMC5779311 DOI: 10.2147/jmdh.s151745] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Aim Article retraction is a measure taken by journals or authors where there is evidence of research misconduct or error, redundancy, plagiarism or unethical research. Recently, the retraction of scientific publications has been on the rise. In this survey, we aimed to describe the characteristics and distribution of retracted articles and the reasons for retractions. Methods We searched retracted articles on the PubMed database and Retraction Watch website from 1980 to February 2016. The primary outcomes were the characteristics and distribution of retracted articles and the reasons for retractions. The secondary outcomes included how article retractions were handled by journals and how to improve the journal practices toward article retractions. Results We included 1,339 retracted articles. Most retracted articles had six authors or fewer. Article retraction was most common in the USA (26%), Japan (11%) and Germany (10%). The main reasons for article retraction were misconduct (51%, n = 685) and error (14%, n = 193). There were 66% (n = 889) of retracted articles having male senior or corresponding authors. Of the articles retracted after August 2010, 63% (n = 567) retractions were reported on Retraction Watch. Large discrepancies were observed in the ways that different journals handled article retractions. For instance, articles were completely withdrawn from some journals, while in others, articles were still available with no indication of retraction. Likewise, some retraction notices included a detailed account of the events that led to article retraction, while others only consisted of a statement indicating the article retraction. Conclusion The characteristics, geographic distribution and reasons for retraction of published articles involving human research participants were examined in this survey. More efforts are needed to improve the consistency and transparency of journal practices toward article retractions.
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Affiliation(s)
- Guowei Li
- Department of Health Research Methods, Evidence, and Impact.,St. Joseph's Healthcare Hamilton.,Centre for Evaluation of Medicines, Programs for Assessment of Technology in Health Research Institute
| | - Mariam Kamel
- Department of Health Research Methods, Evidence, and Impact
| | - Yanling Jin
- Department of Health Research Methods, Evidence, and Impact
| | | | - Lawrence Mbuagbaw
- Department of Health Research Methods, Evidence, and Impact.,St. Joseph's Healthcare Hamilton
| | - Zainab Samaan
- Department of Health Research Methods, Evidence, and Impact.,Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Mitchell Ah Levine
- Department of Health Research Methods, Evidence, and Impact.,St. Joseph's Healthcare Hamilton.,Centre for Evaluation of Medicines, Programs for Assessment of Technology in Health Research Institute.,Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Lehana Thabane
- Department of Health Research Methods, Evidence, and Impact.,St. Joseph's Healthcare Hamilton
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33
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Kostoff RN. Under-reporting of Adverse Events in the Biomedical Literature. JOURNAL OF DATA AND INFORMATION SCIENCE 2017. [DOI: 10.20309/jdis.201623] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Abstract
Purpose
To address the under-reporting of research results, with emphasis on the under-reporting/distorted reporting of adverse events in the biomedical research literature.
Design/methodology/approach
A four-step approach is used: (1) To identify the characteristics of literature that make it adequate to support policy; (2) to show how each of these characteristics becomes degraded to make inadequate literature; (3) to identify incentives to prevent inadequate literature; and (4) to show policy implications of inadequate literature.
Findings
This review has provided reasons for, and examples of, adverse health effects of myriad substances (1) being under-reported in the premiere biomedical literature, or (2) entering this literature in distorted form. Since there is no way to gauge the extent of this under/distorted-reporting, the quality and credibility of the ‘premiere’ biomedical literature is unknown. Therefore, any types of meta-analyses or scientometric analyses of this literature will have unknown quality and credibility. The most sophisticated scientometric analysis cannot compensate for a highly flawed database.
Research limitations
The main limitation is in identifying examples of under-reporting. There are many incentives for under-reporting and few dis-incentives.
Practical implications
Almost all research publications, addressing causes of disease, treatments for disease, diagnoses for disease, scientometrics of disease and health issues, and other aspects of healthcare, build upon previous healthcare-related research published. Many researchers will not have laboratories or other capabilities to replicate or validate the published research, and depend almost completely on the integrity of this literature. If the literature is distorted, then future research can be misguided, and health policy recommendations can be ineffective or worse.
Originality/value
This review has examined a much wider range of technical and non-technical causes for under-reporting of adverse events in the biomedical literature than previous studies.
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Affiliation(s)
- Ronald N. Kostoff
- School of Public Policy , Georgia Institute of Technology , Gainesville , VA 20155 , USA
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34
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Minaya GE, Fuentes-Delgado DJ, Ugalde A, Homedes N. A Missing Piece in Clinical Trial Inspections in Latin America: Interviews With Research Subjects in Peru. J Empir Res Hum Res Ethics 2017; 12:232-245. [PMID: 28728496 DOI: 10.1177/1556264617720756] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Most regulatory agencies conduct clinical trial (CT) site inspections, but the experiences and behaviors of research subjects and their knowledge of the rights and obligations that ensue from participating in a CT are seldom explored. The authors assessed the technical feasibility of incorporating interviews with participants in CT inspections. This article analyzes the responses of 13 CT participants, 14% ( n = 96) of those included in three tuberculosis (TB) CTs. Participants did not object to being interviewed and provided information not obtained during regular inspections. Participants were appreciative of the agency's concern for the integrity of the CT process. Most interviewees did not understand the consent form and were unaware that they were participating in an experiment with unapproved new drugs. Participants' decision to enroll in CT related to undue inducement and therapeutic misconception. Some patients' behaviors, undisclosed to researchers, could have compromised the integrity of the data collected.
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Affiliation(s)
| | | | | | - Núria Homedes
- 3 School of Public Health, The University of Texas, El Paso, TX, USA
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Why published research is untrustworthy. Int Urogynecol J 2017; 28:1271-1274. [PMID: 28707207 DOI: 10.1007/s00192-017-3389-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Accepted: 05/23/2017] [Indexed: 10/19/2022]
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Almutairi AR, Zhou L, Gellad WF, Lee JK, Slack MK, Martin JR, Lo-Ciganic WH. Effectiveness and Safety of Non-vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation and Venous Thromboembolism: A Systematic Review and Meta-analyses. Clin Ther 2017; 39:1456-1478.e36. [PMID: 28668628 DOI: 10.1016/j.clinthera.2017.05.358] [Citation(s) in RCA: 117] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 05/16/2017] [Accepted: 05/30/2017] [Indexed: 12/18/2022]
Abstract
PURPOSE The findings from the observational studies comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) for atrial fibrillation (AF) and venous thromboembolism (VTE) are inconsistent. We conducted separate meta-analyses examining the efficacy/effectiveness and safety of NOACs versus VKAs by disease (AF vs VTE), study design (randomized controlled trials [RCTs] vs observational studies), and NOAC (dabigatran, rivaroxaban, apixaban, and edoxaban). METHODS The main data sources included PubMed/MEDLINE, EMBASE, Web of Science, CINAHL, and Scopus from January 1, 2005, to February 15, 2016. We searched for Phase III RCTs and observational studies comparing NOACs versus VKAs. The primary outcomes were stroke/systemic embolism (SE) for AF; recurrent VTE/fatal pulmonary embolism (PE) for VTE; and major bleeding for both conditions. Secondary outcomes included stroke and myocardial infarction (MI) for AF, recurrent deep vein thrombosis (DVT)/PE for VTE, and mortality, intracranial hemorrhage (ICH), and gastrointestinal bleeding for both conditions. Pooled hazard ratios (HRs) were reported by using inverse variance-weighted random effects models. FINDINGS A total of 13 RCTs and 27 observational studies (AF, n = 32; VTE, n = 8) were included. For AF, dabigatran and VKAs were comparable for stroke/SE risk in 1 RCT (HR, 0.77 [95% CI, 0.57-1.03]) and 6 observational studies (HR, 1.03 [95% CI, 0.83-1.27]). Rivaroxaban had a 20% decreased risk of stroke/SE in 3 RCTs (HR, 0.80 [95% CI, 0.67-0.95]) compared with VKA, but the effect was nonsignificant in 3 observational studies (HR, 0.78 [95% CI, 0.59-1.04]). Apixaban decreased stroke/systemic embolism risk (HR, 0.79 [95% CI, 0.66-0.95]) compared with VKA in 1 RCT, but edoxaban was comparable to VKA (HR, 0.99 [95% CI, 0.77-1.28]) in 1 RCT (no observational studies available for apixaban/edoxaban). Dabigatran, apixaban, and edoxaban decreased the risk of hemorrhagic stroke, mortality, major bleeding, and ICH by 10% to 71% compared with VKAs but not rivaroxaban. For VTE, NOACs and VKAs were comparable for recurrent VTE/fatal PE/DVT/PE risk in 7 RCTs and 1 observational study. The 7 RCTs demonstrated a 32% to 69% decreased risk of major bleeding for dabigatran, rivaroxaban, and apixaban compared with VKAs. No difference was shown in 1 rivaroxaban observational study (HR, 0.77 [95% CI, 0.40-1.49]) and 1 edoxaban RCT (HR, 0.84 [95% CI, 0.59-1.20]). Except for dabigatran, the NOACs had a 61% to 86% decreased risk of ICH and gastrointestinal bleeding. IMPLICATIONS Overall, NOACs were comparable or superior to VKAs. Although no observational studies are currently available for apixaban/edoxaban, a few notable inconsistencies exist for dabigatran (ischemic stroke, MI) and rivaroxaban (stroke/SE, major bleeding in VTE) between RCTs and observational studies. Individualizing NOAC/VKA therapy based on benefit/safety profiles and patient characteristics is suggested.
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Affiliation(s)
- Abdulaali R Almutairi
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, Arizona
| | - Lili Zhou
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, Arizona
| | - Walid F Gellad
- Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Center for Health Equity Research Promotion, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania
| | - Jeannie K Lee
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, Arizona
| | - Marion K Slack
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, Arizona
| | - Jennifer R Martin
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, Arizona; Arizona Health Sciences Library, University Libraries, University of Arizona, Tucson, Arizona
| | - Wei-Hsuan Lo-Ciganic
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, Arizona.
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Benchoufi M, Porcher R, Ravaud P. Blockchain protocols in clinical trials: Transparency and traceability of consent. F1000Res 2017; 6:66. [PMID: 29167732 PMCID: PMC5676196 DOI: 10.12688/f1000research.10531.1] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/17/2017] [Indexed: 11/20/2022] Open
Abstract
Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing the collection of patients' informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we will built a consent workflow using a rising technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. Additionally, it removes the need for third parties, and gives participative control to the peer-to-peer users. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient's consent collection using Blockchain; thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each revision of the protocol, consent was sought again. We obtained a single document, in a standard open format, that accounted for the whole consent collection process: timestamped consent status with regards to each version of the protocol. This document cannot be corrupted, and can be checked on any dedicated public website. It should be considered as a robust proof of data. In the future, we think that the complex data flow of a clinical trial can be tracked using Blockchain. Moreover, a blockchain core functionality, named Smart Contract, can help prevent clinical trial events not to happen in the right chronological order: including patients before they consented or analysing case report forms data before freezing the database. This will help reaching reliability, security, and transparency, and could be a consistent step towards reproducibility.
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Affiliation(s)
| | | | - Philippe Ravaud
- Département d'Epidémiologie Clinique, APHP, Paris, France
- Centre de recherche Inserm Epidémiologie et Statistique Paris Sorbonne Cité (U1153), Université Paris Descartes, Paris, France
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Benchoufi M, Porcher R, Ravaud P. Blockchain protocols in clinical trials: Transparency and traceability of consent. F1000Res 2017; 6:66. [PMID: 29167732 PMCID: PMC5676196 DOI: 10.12688/f1000research.10531.4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/01/2017] [Indexed: 03/14/2024] Open
Abstract
Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients' informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient's consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again. We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security, transparency and could be a consistent step toward reproducibility.
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Affiliation(s)
| | | | - Philippe Ravaud
- Département d'Epidémiologie Clinique, APHP, Paris, France
- Centre de recherche Inserm Epidémiologie et Statistique Paris Sorbonne Cité (U1153), Université Paris Descartes, Paris, France
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Benchoufi M, Porcher R, Ravaud P. Blockchain protocols in clinical trials: Transparency and traceability of consent. F1000Res 2017; 6:66. [PMID: 29167732 PMCID: PMC5676196 DOI: 10.12688/f1000research.10531.5] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/29/2018] [Indexed: 12/30/2022] Open
Abstract
Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients' informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient's consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again. We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security, transparency and could be a consistent step toward reproducibility.
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Affiliation(s)
| | | | - Philippe Ravaud
- Département d'Epidémiologie Clinique, APHP, Paris, France
- Centre de recherche Inserm Epidémiologie et Statistique Paris Sorbonne Cité (U1153), Université Paris Descartes, Paris, France
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40
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Benchoufi M, Porcher R, Ravaud P. Blockchain protocols in clinical trials: Transparency and traceability of consent. F1000Res 2017; 6:66. [PMID: 29167732 PMCID: PMC5676196 DOI: 10.12688/f1000research.10531.2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/24/2017] [Indexed: 03/14/2024] Open
Abstract
Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing the collection of patients' informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we will built a consent workflow using a rising technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. Additionally, it removes the need for third parties, and gives participative control to the peer-to-peer users. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient's consent collection using Blockchain; thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each revision of the protocol, consent was sought again. We obtained a single document, in a standard open format, that accounted for the whole consent collection process: timestamped consent status with regards to each version of the protocol. This document cannot be corrupted, and can be checked on any dedicated public website. It should be considered as a robust proof of data. In the future, we think that the complex data flow of a clinical trial can be tracked using Blockchain. Moreover, a blockchain core functionality, named Smart Contract, can help prevent clinical trial events not to happen in the right chronological order: including patients before they consented or analysing case report forms data before freezing the database. This will help reaching reliability, security, and transparency, and could be a consistent step towards reproducibility.
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Affiliation(s)
| | | | - Philippe Ravaud
- Département d'Epidémiologie Clinique, APHP, Paris, France
- Centre de recherche Inserm Epidémiologie et Statistique Paris Sorbonne Cité (U1153), Université Paris Descartes, Paris, France
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Benchoufi M, Porcher R, Ravaud P. Blockchain protocols in clinical trials: Transparency and traceability of consent. F1000Res 2017; 6:66. [PMID: 29167732 DOI: 10.12688/f1000research.10531.3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/30/2017] [Indexed: 03/14/2024] Open
Abstract
Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing the collection of patients' informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we will built a consent workflow using a rising technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient's consent collection using Blockchain; thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each revision of the protocol, consent was sought again. We obtained a single document, in a standard open format, that accounted for the whole consent collection process: timestamped consent status with regards to each version of the protocol. This document cannot be corrupted, and can be checked on any dedicated public website. It should be considered as a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened in order to remove the need for third parties, here the trial stakeholders, and give participative control to the peer-to-peer users. In the future, we think that the complex data flow of a clinical trial can be tracked using Blockchain, that a blockchain core functionality, named Smart Contract, could help prevent clinical trial events not to happen in the right chronological order: for example including patients before they consented or analysing case report forms data before freezing the database. Globally, we think Blockchain will help with reliability, security, and transparency, and could be a consistent step towards reproducibility.
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Affiliation(s)
| | | | - Philippe Ravaud
- Département d'Epidémiologie Clinique, APHP, Paris, France
- Centre de recherche Inserm Epidémiologie et Statistique Paris Sorbonne Cité (U1153), Université Paris Descartes, Paris, France
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Kault D. The Maimed Martian, credible intervals and bias against benefit. EVIDENCE-BASED MEDICINE 2017; 22:49-53. [PMID: 28073867 DOI: 10.1136/ebmed-2016-110539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
A sad little story about a maimed Martian astronaut is used to illustrate a method of improving confidence interval (CI) calculations. CIs in medical statistics are currently calculated from the data available in a clinical trial or meta-analysis considered in isolation from all other information available on earth. Likewise, the Martian in the story uses only information available to it, in isolation from further information from earth. However, there is further objective knowledge available to people on earth to improve the Martian's estimate. In the same way, we have objective prior knowledge available to us outside of the current clinical trial results which we can use to improve CI calculations. This prior knowledge is incorporated into the CI calculations using Bayesian methods. The objective prior knowledge that is available is the fact that there were researchers who felt it worthwhile to conduct the trial and journal editors who felt it worthwhile publishing the results. It is shown here that the use of this information contracts the width of the log CI by a factor of about three quarters on average. Unlike standard CIs, these new intervals also have the advantage of being directly interpretable in terms of probabilities. These probabilities also enable calculation of improved point estimates. These calculations are applied to 100 randomly selected Cochrane systematic reviews and show serious problems in assessing medical treatments. For treatments not involving new drugs or devices, it is shown that there is evidence of a bias towards a negative assessment. The calculations here make a quantitative adjustment for publication bias. They show that the proportion of negative assessments do not reflect an appropriate adjustment for publication bias.
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Affiliation(s)
- David Kault
- College of Science and Engineering, James Cook University, Townsville, Queensland, Australia
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Knepper D, Fenske C, Nadolny P, Bedding A, Gribkova E, Polzer J, Neumann J, Wilson B, Benedict J, Lawton A. Detecting Data Quality Issues in Clinical Trials: Current Practices and Recommendations. Ther Innov Regul Sci 2016; 50:15-21. [DOI: 10.1177/2168479015620248] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Wiedermann CJ. Ethical publishing in intensive care medicine: A narrative review. World J Crit Care Med 2016; 5:171-179. [PMID: 27652208 PMCID: PMC4986546 DOI: 10.5492/wjccm.v5.i3.171] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 05/19/2016] [Accepted: 07/18/2016] [Indexed: 02/07/2023] Open
Abstract
Ethical standards in the context of scientific publications are increasingly gaining attention. A narrative review of the literature concerning publication ethics was conducted as found in PubMed, Google Scholar, relevant news articles, position papers, websites and other sources. The Committee on Publication Ethics has produced guidelines and schedules for the handling of problem situations that have been adopted by professional journals and publishers worldwide as guidelines to authors. The defined requirements go beyond the disclosure of conflicts of interest or the prior registration of clinical trials. Recommendations to authors, editors and publishers of journals and research institutions were formulated with regard to issues of authorship, double publications, plagiarism, and conflicts of interest, with special attention being paid to unethical research behavior and data falsification. This narrative review focusses on ethical publishing in intensive care medicine. As scientific misconduct with data falsification damage patients and society, especially if fraudulent studies are considered important or favor certain therapies and downplay their side effects, it is important to ensure that only studies are published that have been carried out with highest integrity according to predefined criteria. For that also the peer review process has to be conducted in accordance with the highest possible scientific standards and making use of available modern information technology. The review provides the current state of recommendations that are considered to be most relevant particularly in the field of intensive care medicine.
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Abstract
Abstract
This article discusses the responsible conduct of research, questionable research practices, and research misconduct. Responsible conduct of research is often defined in terms of a set of abstract, normative principles, professional standards, and ethics in doing research. In order to accommodate the normative principles of scientific research, the professional standards, and a researcher’s moral principles, transparent research practices can serve as a framework for responsible conduct of research. We suggest a “prune-and-add” project structure to enhance transparency and, by extension, responsible conduct of research. Questionable research practices are defined as practices that are detrimental to the research process. The prevalence of questionable research practices remains largely unknown, and reproducibility of findings has been shown to be problematic. Questionable practices are discouraged by transparent practices because practices that arise from them will become more apparent to scientific peers. Most effective might be preregistrations of research design, hypotheses, and analyses, which reduce particularism of results by providing an a priori research scheme. Research misconduct has been defined as fabrication, falsification, and plagiarism (FFP), which is clearly the worst type of research practice. Despite it being clearly wrong, it can be approached from a scientific and legal perspective. The legal perspective sees research misconduct as a form of white-collar crime. The scientific perspective seeks to answer the following question: “Were results invalidated because of the misconduct?” We review how misconduct is typically detected, how its detection can be improved, and how prevalent it might be. Institutions could facilitate detection of data fabrication and falsification by implementing data auditing. Nonetheless, the effect of misconduct is pervasive: many retracted articles are still cited after the retraction has been issued.
Main points
Researchers systematically evaluate their own conduct as more responsible than colleagues, but not as responsible as they would like.
Transparent practices, facilitated by the Open Science Framework, help embody scientific norms that promote responsible conduct.
Questionable research practices harm the research process and work counter to the generally accepted scientific norms, but are hard to detect.
Research misconduct requires active scrutiny of the research community because editors and peer-reviewers do not pay adequate attention to detecting this. Tips are given on how to improve your detection of potential problems.
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Dobesh PP, Fanikos J. Reducing The Risk Of Stroke In Patients With Nonvalvular Atrial Fibrillation With Direct Oral Anticoagulants. Is One Of These Not Like The Others? J Atr Fibrillation 2016; 9:1481. [PMID: 27909544 PMCID: PMC5129697 DOI: 10.4022/jafib.1481] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2016] [Revised: 08/16/2016] [Accepted: 08/17/2016] [Indexed: 12/29/2022]
Abstract
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and increases risk of stroke by nearly 5-fold. While warfarin has been employed successfully to reduce the risk of stroke in these patients, there are a number of challenges with therapy. These include the need for therapeutic monitoring due to variability in patient response, frequent dose adjustments, numerous drug-drug, drug-food, and drug-disease interactions, and a heightened risk of thrombosis and bleeding due to these issues. Current guidelines recommend that the vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs) should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events. The DOACs include the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. In clinical trials these agents consistently demonstrated a reduction in the risks of hemorrhagic stroke and intracranial hemorrhage compared to VKA. Clinicians now must decide if there are meaningful differences between these agents in order to prescribe the best agent for an individual patient. Therefore, it is critical for clinicians to go beyond information provided in manuscript abstracts, and gain an understanding of the similarities and differences in clinical trial design, patient enrollment, and statistical analysis.
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Affiliation(s)
- Paul P Dobesh
- University of Nebraska Medical Center College of Pharmacy, 986145 Nebraska Medical Center, Omaha, NE, USA
| | - John Fanikos
- Department of Pharmacy, Brigham and Women's Hospital, Boston, MA
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Abstract
The medical literature is prone to overstating results, a condition not thoroughly recognized among policymakers. This article sets forth examples of potential problems with research integrity in the infectious disease literature. We describe articles that may be spun, categories lumped together in hopes of creating a significant effect (and sometimes an insignificant one), changes in metrics, and how trials may fail because of suboptimal interventions. When examined together, the examples show that the problems are widespread and illustrate the difficulty associated with interpreting medical research. The state of the current medical literature makes it of utmost importance that all sections of the manuscript are read, including associated letters to the editors and information on ClinicalTrials.gov before authors' recommendations are accepted.
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Fraud, individuals, and networks: A biopsychosocial model of scientific frauds. Sci Justice 2016; 56:109-12. [DOI: 10.1016/j.scijus.2016.01.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2015] [Revised: 11/02/2015] [Accepted: 01/28/2016] [Indexed: 11/22/2022]
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Amarilyo G, Furst DE, Woo JMP, Li W, Bliddal H, Christensen R, Tarp S. Agreements and Discrepancies between FDA Reports and Journal Papers on Biologic Agents Approved for Rheumatoid Arthritis: A Meta-Research Project. PLoS One 2016; 11:e0147556. [PMID: 26808309 PMCID: PMC4725722 DOI: 10.1371/journal.pone.0147556] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Accepted: 01/05/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Sponsors that seek to commercialize new drugs apply to the Food and Drug Administration (FDA) which independently analyzes the raw data and reports the results on its website. OBJECTIVES This study sought to determine if there are differences between the FDA assessments and journal reports on biologic agents developed for the treatment of rheumatoid arthritis. METHODS Available data on FDA-approved drugs were extracted from the website, and a systematic literature search was conducted to identify matching studies in peer-reviewed medical journals. Outcome measures were the American College of Rheumatology response criteria ACR20 (efficacy) and withdrawal due to adverse events (safety). As effect size odds ratios were estimated for each active trial arm vs. control arm (i.e. for both sources: FDA and journal report), followed by calculation of the ratios of the FDA and journal report odds ratios. A ratio of odds ratios not equal to 1 was categorized as a discrepancy. RESULTS FDA reports were available for 8 of 9 FDA-approved biologic agents for rheumatoid arthritis; all identified trials (34) except one were published in peer-reviewed journals. Overall, discrepancies were noted for 20 of the 33 evaluated trials. Differences in the apparent benefit reporting were found in 39% (24/61) pairwise comparisons and in 11 cases these were statistically significant; the FDA report showed greater benefit than the journal publication in 15 comparisons and lesser benefit in 9. Differences in the reported harms were found in 51% (28/55) pairwise comparisons and were statistically significant in 5. The "signal" in FDA reports showed a less harmful effect than the journal publication in 17 comparisons whereas a more harmful effect in 11. The differences were attributed to differences in analytic approach, patient inclusion, rounding effect, and counting discrepancies. However, no differences were categorized as critical. CONCLUSION There was no empirical evidence to suggest biased estimates between the two sources. Increased and detailed transparency in publications would improve the understanding and credibility of published results. Further, the FDA report was found to be a useful source when data are missing in the published report (i.e. reporting bias).
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Affiliation(s)
- Gil Amarilyo
- Pediatric Rheumatology Unit, Schneider Children's Medical Center of Israel, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Daniel E. Furst
- David Geffen School of Medicine, University of California, Los Angeles, California, United States of America
| | - Jennifer M. P. Woo
- David Geffen School of Medicine, University of California, Los Angeles, California, United States of America
| | - Wen Li
- David Geffen School of Medicine, University of California, Los Angeles, California, United States of America
| | - Henning Bliddal
- Musculoskeletal Statistics Unit, The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Robin Christensen
- Musculoskeletal Statistics Unit, The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Simon Tarp
- Musculoskeletal Statistics Unit, The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
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McCrae N, Purssell E. Eligibility criteria in systematic reviews published in prominent medical journals: a methodological review. J Eval Clin Pract 2015; 21:1052-8. [PMID: 26370723 DOI: 10.1111/jep.12448] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/11/2015] [Indexed: 12/14/2022]
Abstract
RATIONALE AND AIM Clear and logical eligibility criteria are fundamental to the design and conduct of a systematic review. This methodological review examined the quality of reporting and application of eligibility criteria in systematic reviews published in three leading medical journals. METHODS All systematic reviews in the BMJ, JAMA and The Lancet in the years 2013 and 2014 were extracted. These were assessed using a refined version of a checklist previously designed by the authors. RESULTS A total of 113 papers were eligible, of which 65 were in BMJ, 17 in The Lancet and 31 in JAMA. Although a generally high level of reporting was found, eligibility criteria were often problematic. In 67% of papers, eligibility was specified after the search sources or terms. Unjustified time restrictions were used in 21% of reviews, and unpublished or unspecified data in 27%. Inconsistency between journals was apparent in the requirements for systematic reviews. CONCLUSIONS The quality of reviews in these leading medical journals was high; however, there were issues that reduce the clarity and replicability of the review process. As well as providing a useful checklist, this methodological review informs the continued development of standards for systematic reviews.
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Affiliation(s)
- Niall McCrae
- Florence Nightingale Faculty of Nursing & Midwifery, King's College London, London, UK
| | - Edward Purssell
- Florence Nightingale Faculty of Nursing & Midwifery, King's College London, London, UK
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