The Role and Importance of Clinical Trial Registries and Results Databases
|
|
- Nigel Reynard Gilbert
- 6 years ago
- Views:
Transcription
1 The Role and Importance of Clinical Trial Registries and Results Databases March 2014 Rebecca J. Williams, Pharm.D., MPH Assistant Director, ClinicalTrials.gov National Library of Medicine, National Institutes of Health
2 Outline Public health view of clinical trial disclosure Key U.S. disclosure policies and laws Issues in reporting Uses of public registries Emerging issues in clinical trial disclosure 2
3 Why Conduct Clinical Trials? To obtain new and generalizable knowledge To contribute to the evidence base to inform medical decision making 3
4 How It s Supposed to Work Clinical Trials Health Outcomes Journals FDA Reviews Systematic Reviews Meta-analyses Guidelines Informed Decisions 4
5 Evidence Based Medicine Clinical and policy decisions should be informed by evidence regarding the benefits, risks, and other burdens associated with all possible alternatives Clinical trials are a key component of the body of scientific evidence that must be used to make decisions Most decision makers depend on summary data from journal publications 5
6 Publications: Three Key Issues Not all trials are published in the literature Publications do not always include all prespecified outcome measures or complete adverse event information Unacknowledged changes made to the trial protocol that would affect the interpretation of the findings e.g., changes to the pre-specified outcome measures 6
7 7
8 Figure 1. Effect of FDA Regulatory Decisions on Publication Turner EH et al. N Engl J Med 2008;358:
9 9
10 Summary of Findings Fewer than half of NIH funded trials registered at ClinicalTrials.gov after September 2005 and completed by December 2008 were published in a peer reviewed biomedical journal indexed by MEDLINE within 30 months of trial completion After a median of 51 months after study completion, a third of NIH-funded trials in the sample remained unpublished Ross JS et al. BMJ 2012;344:d
11 Kaplan-Meier estimates for ulcer complications according to traditional definition. Results are truncated after 12 months, no ulcer complications occurred after this period. Adapted from Lu Jüni P, Rutjes AW, Dieppe PA. BMJ. 2002;324(7349):
12 Internal Corporate They swallowed our story, hook, line and sinker 12 Thomas K. NY Times. June 24,
13 Publications: Three Key Issues Not all trials are published in the literature Publications do not always include all prespecified outcome measures or complete adverse event information Unacknowledged changes made to the trial protocol that would affect the interpretation of the findings e.g., changes to the pre-specified outcome measures 13
14 Impact of Issues Incomplete disclosure of research results impedes scientific process Lack of availability of clinical trial data is particularly problematic: Trials depend on human volunteers Trial results inform our medical decisions 14 14
15 What Methods are Available to Counter Such Issues?
16 Clinical Trial Disclosure Zarin DA, Tse T. Science
17 Definitions Registration: the process for making key summary information about interventional studies using human volunteers accessible to the public via a web-based system, from study initiation to completion Results Reporting: making summary information about study results available in a structured, publicly accessible web-based results database 17
18 Rationale for Trial Disclosure Simes (1986) - Call for systematic registration to mitigate publication bias Declaration of Helsinki (2008; 2013 revised) Article 35: Registration of all research studies involving human subjects Article 36: Disclosure of negative and inconclusive as well as positive results World Health Organization: The registration of all interventional studies is a scientific, ethical, and moral responsibility. 18
19 Rationale for Trial Disclosure Category Human subject protections Research integrity Evidence-based medicine Allocation of resources Reasons Allow potential participants to find studies Assist ethical review boards and others to determine appropriateness of studies being reviewed (e.g., harms, benefits, redundancy) Promote fulfillment of ethical responsibility to human volunteers research contributes to medical knowledge Facilitates tracking of protocol changes Enhances transparency of research enterprise Facilitates tracking of studies and outcome measures Allows more complete identification of relevant studies Promotes more efficient allocation of resources (e.g., investigators, institutional review boards [IRBs], volunteers, funders) 19
20 History of ClinicalTrials.gov FDA Modernization Act (FDAMA) IND trials of serious and life-threatening conditions 2000 ClinicalTrials.gov launched Calls for increased transparency of clinical trials State Attorneys General; Maine state law International Committee of Medical Journal Editors (ICMJE)/World Health Organization (WHO) FDA Amendments Act (FDAAA) Expands registration scope & adds results reporting 2008 Declaration of Helsinki (updated 2013) IND = investigational new drug application 20
21 Number of Registered Studies Over Time (Data as of February 27, 2014) ~ 400 per week ~25-30 new records per week ~ per week 21
22 Two Key Disclosure Policies ICMJE Journal Editors (2005) Prospective registration of all clinical trials as a condition for publication of the study results FDA Amendments Act, Section 801 (2007) Expanded trial registration requirements (FDAMA 113) to include trials of devices and additional trials of drugs Added new results submission requirement Added enforcement provisions Civil monetary penalties (up to $10,000/day) Withholding of NIH grant funds Current status: Rulemaking pending 22
23 Why? Which Trials? ICMJE Required for journal publication Interventional Studies - All Phases - All Intervention Types FDAAA Required by US federal law Interventional Studies - Not Phase 1/Feasibility - Drugs, Biologics, Devices Who? Author Sponsor or designated PI When to Register? Prior to enrollment of first participant Within 21 days of enrollment of first participant What to Register? WHO Data Items ClinicalTrials.gov and FDAAA Data Elements Where to Register? When to Submit Results? ClinicalTrials.gov or WHO Primary Registry Not Applicable 23 ClinicalTrials.gov Within 12 months of final data collection for the primary outcome
24 Interventional vs. Observational Interventional Study ( Clinical Trial ) Participants assigned to receive one or more (or no) interventions based on a protocol Observational Study Participants identified as belonging to study groups, not assigned by researcher [Currently excluded from most registration policies, but increasing attention to this topic] Note: Many Diagnostic studies are interventional
25 Scope of Registry ClinicalTrials.gov permits the registration of any biomedical or health-related research studies in humans that meet the following two requirements: 1.Conformance with any applicable human subject protections or ethics review regulations (or equivalent) (e.g., institutional review board (IRB) approval) AND 2.Conformance with any applicable regulations of the national (or regional) health authority (or equivalent)
26 ClinicalTrials.gov Home Page 26
27 ClinicalTrials.gov Statistics (as of 2/27/2014) 98 million pages views monthly 64,000 unique visitors daily Registration Results Total 162,059 11,513 Type of Trial Observational 30,272 (18%) 740 (6%) Interventional* 131,037 (80%) 10,773 (93%) - Drug & Biologic 85, Behavioral, Other 33,749 1,346 - Surgical Procedure 14, Device** 12,204 1,052 * Intervention types not additive; study record may include more than one type of intervention **518 applicable device clinical trials submitted, but qualify for delayed posting under FDAAA
28 Content of ClinicalTrials.gov Records One record per trial Registration section Submitted at trial initiation Summarizes trial protocol Condition Interventions Design, etc Includes recruitment information (e.g., eligibility, locations) Results section Submitted after trial completion Summarizes trial results Participant Flow Baseline Characteristics Outcome Measures (including statistical analyses) Adverse Events 28
29 Public Archive for Records Changes can and should be made to records Estimated dates become actual dates Estimated enrollment becomes actual Other protocol changes Overall recruitment status changes Results may be added or changed All changes are publicly tracked 29
30 Stages in Disclosure Parallel the Research Life Cycle 30
31 Results Database Objectives Satisfy legal requirements Promote objective, standardized reporting Facilitate good reporting practices, including publishing (e.g., CONSORT) and regulatory guidelines Provide structured data entry to ensure complete reporting, efficient quality review, and consistent display of data elements Support detailed searches with the use of database structure and other NLM functions Adapted from Table 2 in Zarin DA et al. N Engl J Med 2011;
32 Sample Publication and Results Posted at ClinicalTrials.gov* *Adapted from NCT
33 33 33
34 34 34
35 35
36 CONSORT Flow Diagram 2010 by British Medical Journal Publishing Group Shulz KF, Altman DG, Moher D. BMJ 2010;340:
37 CONSORT Flow Diagram ( Figure 1 ) Pappas PG, Chetchotisakd P, Larsen RA et al. Clin Infect Dis 2009;48:
38 ClinicalTrials.gov Format Participant Flow: Overall Study AmphoB Standard AmphoB + Fluc400 AmphoB + Fluc800 STARTED Treated [1] 49 [2] Day 14 visit days therapy COMPLETED 36 [3] 33 [3] 31 [3] NOT COMPLETED Study Ineligible Missed Day 112 Follow-up [1] 2 subjects randomized to AmphoB received AmphoB+Fluc400 [2] 3 subjects randomized to AmphoB+Fluc400 received AmphoB+Fluc800 [3] Completed Day 112 Follow-up Adapted from NCT
39 Baseline Data Journal Article Format ( Table 1 ) Pappas PG, Chetchotisakd P, Larsen RA et al. Clin Infect Dis 2009;48: Infectious Diseases Society of America 39
40 ClinicalTrials.gov Format NCT
41 Outcome Measures Journal Article Format Pappas PG, Chetchotisakd P, Larsen RA et al. Clin Infect Dis 2009;48: Infectious Diseases Society of America 41
42 ClinicalTrials.gov Format NCT
43 ClinicalTrials.gov Format (cont.) NCT
44 ClinicalTrials.gov Format NCT
45 ClinicalTrials.gov Format NCT
46 Clarifications about Results Reporting Requirements Does NOT prescribe how study should be conducted Summary results at the end of the trial No interim or real time reporting No participant level reporting Information currently targeted at readers of the medical literature Tables of information; just the facts No conclusions or discussion 46
47 Registration, Results Submission and Publication Deadline for submitting results to ClinicalTrials.gov is independent of publication status Submitting results to ClinicalTrials.gov will not interfere with publication* Failure to register WILL interfere with publication! ClinicalTrials.gov records are linked, via NCT number, to publications Ensure the registration record is up-to-date ~ 50% of ClinicalTrials.gov results not initially available elsewhere (Zarin et al. N Engl J Med 2011: ) *Laine C et al. Ann Intern Med. 2007; 47
48 Linking Publications to NCT Numbers 48
49 Issues in reporting 49
50 Outcome Measures, in theory The primary outcome measure is pre-specified as part of the protocol Basis for the power calculation/determining sample size Pre-specification is key to the conduct of statistical analysis The primary outcome measure is registered in a public database at trial initiation 50
51 Outcome Measures, in practice Studies with results in ClinicalTrials.gov (n=2,178) Primary Outcome Measures Median: 1 Interquartile range: 1 2 Full range: 1 71 Secondary Outcome Measures Median: 3 Interquartile range: 1 7 Full range: Zarin DA et al. N Engl J Med 2011;364:
52 Outcomes Conceptual Framework N Engl J Med 2011;364:
53 SPIRIT 2013 Statement Item 12 Outcomes Primary, Secondary, Other Specific measurement variable (e.g., systolic blood pressure) Analysis metric (e.g., change from baseline, final value, time to event) Method of aggregation (e.g., median, proportion) Time point Chan A et al. Ann Intern Med. 2013;158:
54 Level of Outcome Measure Specification in Registration Primary Outcome Measures registered in ClinicalTrials.gov Level Primary Outcome Measures (% Total); n=100 1 Domain only 36% 2 Specific Measurement 25% 3 Specific Metric 26% 4 Method of Aggregation 13% Specific Time Frame 72% Zarin DA et al. N Engl J Med 2011;364:
55 Experience with Results Database There is no substitute for a well-written protocol (and registration record) It is never too early to plan for results reporting! 55 55
56 General Review Criteria Protocol and results must be clear and informative Review focuses on: Logic and internal consistency Apparent validity Meaningful entries Formatting, including appropriate use of database structure Not equivalent to peer review; not verified against external sources (e.g., full protocol) Review Criteria: 56
57 Problems with Results Entries Time to survival 823 hours of sleep/day Time to response: 12 participants Number of participants changes dramatically between modules 57
58 Outcome Measure - Example 1. Primary Outcome Measure: Measure Title Measure Description Time Frame Safety Issue? Percent Change in Hemoglobin A1c A1C will be measured at baseline and after 12 and 24 weeks of treatment. 24 weeks Yes Measured Values Remuverol Placebo Number of Participants Analyzed Percent Change in Hemoglobin A1c [units: participants %] Least Squares Mean ± Standard Error ± ± 0.12
59 Outcome Measure - Example 1. Primary Outcome Measure: Measure Title Measure Description Time Frame Safety Issue? Percent Reduction in Percentage of Migraine Days per 30 Days Change in the percentage of migraine days per 30 days relative to the OAT run-in (Month 1). Assessed by participant electronic diary. 24 weeks Yes Measured Values Hypertena Placebo Number of Participants Analyzed Percent Reduction in Percentage of Migraine Days per 30 Days [units: percent] Mean ± Standard Deviation 15.0 ± ± 6.8
60 Uses of ClinicalTrials.gov 60
61 Basic Uses of ClinicalTrials.gov Identify trials of potential interest for an individual Including to specific user communities such as: Breast cancer (e.g., Track progress of a specific trial, including availability of summary results Identify all trials that are completed or ongoing for a specific set of conditions/interventions Complement to literature review Useful in planning stages of a new protocol Identify investigators and/or research centers of relevance to a specific set of conditions/ interventions 61
62 Trials in Acute Kidney Injury (AKI) 126 ongoing trials registered in ClinicalTrials.gov 65% (n=82) prevention trials Appropriate Sample Size with Adequate Power? Accurate estimate of incidence of AKI in group studied Realistic estimate of the effect of the intervention Outcome: Number of Participants with AKI with need for RRT (Renal Replacement Therapy) Estimated that 822 participants per arm needed Only 3 of 28 contrast studies and 3 of 30 cardiac surgery studies had more than 800 participants TOTAL Clin J Am Soc Nephrol. 2012;7:
63 Other Uses of ClinicalTrials.gov Examination of the Clinical Research Enterprise Clinical Trials Transformation Initiative (CTTI) Creating and maintaining a research data set for aggregate analysis of ClinicalTrials.gov Initial publication in JAMA in May 2012 Clinical specialty analyses also published: oncology, cardiovascular, and peripheral vascular disease Assess quality and completeness of reporting Fidelity of reports to research protocol Publication bias 63
64 Conclusion: Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs. JAMA. 2012;307(17):
65 Conclusions Clinical trials are critical for advancing knowledge and informing medical decisions Clinical trials require careful planning, use of clinically relevant outcomes, and appropriately trained personnel to ensure good conduct Results disclosure needs to be considered in the planning stages of a protocol What will be collected? How will it be analyzed and summarized? Who is responsible? 65
66 Thank you! Acknowledgement: Deborah Zarin and Tony Tse for permission to use their slide content 66
67 Additional Background Califf RM, Zarin DA, Kramer JM, Sherman RE, Aberle LH, Tasneem A. Characteristics of Clinical Trials Registered in ClinicalTrials.gov, JAMA May 2;307(17): Ross JS, Tse T, Zarin DA, Xu H, Zhou L, Krumholz HM. Publication of NIH funded trials registered in ClinicalTrials.gov: cross-sectional analysis. BMJ 2012;344:d7292. Zarin DA, Tse T, Williams RJ, Califf RM, Ide NC. The ClinicalTrials.gov results database--update and key issues. N Engl J Med Mar 3;364(9): Tse T, Williams RJ, Zarin DA. Reporting basic results in ClinicalTrials.gov. Chest 2009;136:
68 68
69 Case Study Outcome Measures Ann Intern Med. 2013;159:
70 NCT Initial and Updated Entries for Primary Outcome Measures Level of Specification Domain (e.g., anxiety ) Specific measurement (e.g., Hamilton Anxiety Rating Scale ) Specific metric (e.g., change from baseline ) Method of aggregation (e.g., proportion of participants with decrease 50% ) Time frame (e.g., 12 weeks ) Initial ClinicalTrials.gov Entry Hidradenitis suppurativa PGA (Physician s Global Assessment) N/A N/A Updated ClinicalTrials.gov Entry Hidradenitis suppurativa PGA Change from baseline Percentage of participants achieving a clinical response, defined as a PGA score of clear, minimal, or mild with at least a 2-grade reduction indicating improvement Week 16 Baseline, week 16 Zarin DA, Tse T. Ann Intern Med Jul 2;159(1):
71 NCT Initial and Updated Entries for Primary Outcome Measures Level of Specification Domain (e.g., anxiety ) Specific measurement (e.g., Hamilton Anxiety Rating Scale ) Specific metric (e.g., change from baseline ) Method of aggregation (e.g., proportion of participants with decrease 50% ) Time frame (e.g., 12 weeks ) Initial ClinicalTrials.gov Entry Depression HAM-D (Hamilton Depression Rating Scale) N/A N/A Zarin DA, Tse T. Ann Intern Med Jul 2;159(1):65 7. Updated ClinicalTrials.gov Entry Depression MADRS (Montgomery Asberg Depression Rating Scale) MADRS score 13 during time frame Percentage of participants with specific metric 24 weeks 50 weeks after receiving intervention for participants with HCV genotype 1 or 4 OR 26 weeks after receiving intervention for patients with HCV genotype 2 or 3 71
Thursday, April 23. Incorporating ClinicalTrials.gov Into Patient Education and Care Coordination. Session 1:30 3 pm Valencia BC
Session 1:30 3 pm Valencia BC Incorporating ClinicalTrials.gov Into Patient Education and Care Coordination Clinical trials play a significant role in improving cancer treatment, symptom management, and
More informationTitle 1 Descriptive title identifying the study design, population, interventions, and, if applicable, trial acronym
SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents* Section/item Item No Description Addressed on page number Administrative information Title 1 Descriptive
More informationThe QUOROM Statement: revised recommendations for improving the quality of reports of systematic reviews
The QUOROM Statement: revised recommendations for improving the quality of reports of systematic reviews David Moher 1, Alessandro Liberati 2, Douglas G Altman 3, Jennifer Tetzlaff 1 for the QUOROM Group
More informationClinicalTrials.gov a programmer s perspective
PhUSE 2009, Basel ClinicalTrials.gov a programmer s perspective Ralf Minkenberg Boehringer Ingelheim Pharma GmbH & Co. KG PhUSE 2009, Basel 1 Agenda ClinicalTrials.gov Basic Results disclosure Initial
More informationReporting Discrepancies between the ClinicalTrials.gov Results Database and Peer Reviewed Publications
Reporting Discrepancies between the ClinicalTrials.gov Results Database and Peer Reviewed Publications Hartung, D. M., Zarin, D. A., Guise, J. M., McDonagh, M., Paynter, R., & Helfand, M. (2014). Reporting
More informationClinicalTrials.gov Registration User s Guide. January 2018
ClinicalTrials.gov Registration User s Guide January 2018 ClinicalTrials.gov Assistance and Training at WCM Contact the WCM ClinicalTrials.gov Administrator at registerclinicaltrials@med.cornell.edu to:
More informationRace and Ethnicity Reporting in Clinical Research and Its Role In Pragmatic Clinical Trials February 28, 2014
Race and Ethnicity Reporting in Clinical Research and Its Role In Pragmatic Clinical Trials February 28, 2014 Monique Anderson, MD Medical Instructor Duke Clinical Research Institute Duke University Medical
More informationCONSORT 2010 checklist of information to include when reporting a randomised trial*
CONSORT 2010 checklist of information to include when reporting a randomised trial* Section/Topic Title and abstract Introduction Background and objectives Item No Checklist item 1a Identification as a
More informationInstrument for the assessment of systematic reviews and meta-analysis
Appendix II Annex II Instruments for the assessment of evidence As detailed in the main body of the methodological appendix (Appendix II, "Description of the methodology utilised for the collection, assessment
More informationThe Research Registryâ Guidebook
The Research Registryâ Guidebook March 2017 Contents Section 1: Registering a study on the Research Registryâ 3 An Introduction to the Research Registryâ 3 Support and endorsements 3 Data security 3 What
More informationNIH NEW CLINICAL TRIAL REQUIREMENTS AND FORMS-E
NIH NEW CLINICAL TRIAL REQUIREMENTS AND FORMS-E HOW DOES THE NIH DEFINE CLINICAL TRIAL AND HOW DO I KNOW IF MY STUDY IS ONE? 01-18-18 A clinical trial is defined by the NIH as a research study in which
More informationPediatric Anti-bacterial and Anti-fungal Trials from 2007 to 2015: A Systematic Review of ClinicalTrials.gov
Pediatric Anti-bacterial and Anti-fungal Trials from 2007 to 2015: A Systematic Review of ClinicalTrials.gov Joshua Thaden, MD, PhD Fellow, Infectious Diseases Duke University April 5, 2016 Objectives
More informationSchool of Dentistry. What is a systematic review?
School of Dentistry What is a systematic review? Screen Shot 2012-12-12 at 09.38.42 Where do I find the best evidence? The Literature Information overload 2 million articles published a year 20,000 biomedical
More informationRARE-Bestpractices Conference
RARE-Bestpractices Conference 24 November 2016, Istituto Superiore di Sanità, Rome, Italy Avoiding waste in production, design and conduct of studies and reporting evidence on rare diseases Philippe Ravaud
More informationEmpirical evidence on sources of bias in randomised controlled trials: methods of and results from the BRANDO study
Empirical evidence on sources of bias in randomised controlled trials: methods of and results from the BRANDO study Jonathan Sterne, University of Bristol, UK Acknowledgements: Tony Ades, Bodil Als-Nielsen,
More informationAmyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry
Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding
More informationEQUATOR Network: promises and results of reporting guidelines
EQUATOR Network: promises and results of reporting guidelines Doug Altman The EQUATOR Network Centre for Statistics in Medicine, Oxford, UK Key principles of research publications A published research
More informationGuidance for Industry Migraine: Developing Drugs for Acute Treatment
Guidance for Industry Migraine: Developing Drugs for Acute Treatment DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft
More informationSystematic Review & Course outline. Lecture (20%) Class discussion & tutorial (30%)
Systematic Review & Meta-analysisanalysis Ammarin Thakkinstian, Ph.D. Section for Clinical Epidemiology and Biostatistics Faculty of Medicine, Ramathibodi Hospital Tel: 02-201-1269, 02-201-1762 Fax: 02-2011284
More informationMigraine: Developing Drugs for Acute Treatment Guidance for Industry
Migraine: Developing Drugs for Acute Treatment Guidance for Industry U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) February 2018
More informationRandomized Controlled Trial
Randomized Controlled Trial Training Course in Sexual and Reproductive Health Research Geneva 2016 Dr Khalifa Elmusharaf MBBS, PgDip, FRSPH, PHD Senior Lecturer in Public Health Graduate Entry Medical
More informationCochrane Breast Cancer Group
Cochrane Breast Cancer Group Version and date: V3.2, September 2013 Intervention Cochrane Protocol checklist for authors This checklist is designed to help you (the authors) complete your Cochrane Protocol.
More informationClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: June 25, ClinicalTrials.gov ID: NCT
ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: June 25, 2014 ClinicalTrials.gov ID: NCT00372385 Study Identification Unique Protocol ID: VX05-950-104EU Brief Title:
More informationPreparing a US FDA Medical Device 510(K) Submission
Preparing a US FDA Medical Device 510(K) Submission If you want to introduce your medical device to the US market, you need to obtain clearance from the FDA. This clearance is obtained from the FDA via
More informationCTRI Dataset and Description
CTRI Dataset and Description CTRI Field Description Public title of study Title intended for the lay public in easily understood language. Example: A clinical trial to study the effects of two drugs, ramipril
More informationSystematic reviews and meta-analyses of observational studies (MOOSE): Checklist.
Systematic reviews and meta-analyses of observational studies (MOOSE): Checklist. MOOSE Checklist Infliximab reduces hospitalizations and surgery interventions in patients with inflammatory bowel disease:
More informationThe following page contains the final YODA Project review approving this proposal.
The YODA Project Research Proposal Review The following page contains the final YODA Project review approving this proposal. The Yale University Open Data Access (YODA) Project Yale University Center for
More informationUNIVERSITY OF SPLIT Universitas Studiorum Spalatensis. SCHOOL OF MEDICINE Facultas Medica SHELLY MELISSA PRANIĆ
UNIVERSITY OF SPLIT Universitas Studiorum Spalatensis SCHOOL OF MEDICINE Facultas Medica SHELLY MELISSA PRANIĆ ADEQUACY OF REGISTRATION AND RESULTS REPORTING OF RANDOMIZED CONTROLLED TRIALS IN CLINICALTRIALS.GOV
More informationTitle: Intention-to-treat and transparency of related practices in randomized, controlled trials of anti-infectives
Author s response to reviews Title: Intention-to-treat and transparency of related practices in randomized, controlled trials of anti-infectives Authors: Robert Beckett (rdbeckett@manchester.edu) Kathryn
More informationYale University. Open Data Access Project
Open Data Access Project A Model for Dissemination and Independent Analysis of Clinical Trial Program Data Yale University What if. Yale University Merck concluded that the cardiovascular effects
More informationControlled Trials. Spyros Kitsiou, PhD
Assessing Risk of Bias in Randomized Controlled Trials Spyros Kitsiou, PhD Assistant Professor Department of Biomedical and Health Information Sciences College of Applied Health Sciences University of
More informationAppendices. Appendix A Search terms
Appendices Appendix A Search terms Database Search terms Medline 1. Ipilimumab; 2. MDX-010; 3. MDX-101; 4. Yervoy; 5. BMS-734016; 6. Nivolumab; 7. ONO-4538; 8. BMS-936558; 9. MDX-1106; 10. Opdivo; 11.
More informationThe SPIRIT Initiative: Defining standard protocol items
The SPIRIT Initiative: Defining standard protocol items October 11, 2012 An-Wen Chan, MD DPhil Women s College Hospital & Research Institute University of Toronto Importance of trial protocols Trial registries
More informationPROSPERO International prospective register of systematic reviews
PROSPERO International prospective register of systematic reviews Review title and timescale 1 Review title Give the working title of the review. This must be in English. Ideally it should state succinctly
More informationPrevious Study Return to List Next Study
A service of the U.S. National Institutes of Health Trial record 1 of 1 for: 42603ATT3013 Previous Study Return to List Next Study A Study to Evaluate Effectiveness and Safety of Prolonged Release OROS
More informationGuidelines for Reporting Non-Randomised Studies
Revised and edited by Renatus Ziegler B.C. Reeves a W. Gaus b a Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, Great Britain b Biometrie und Medizinische Dokumentation,
More informationWHO Statement on Improving Availability and Transparency of Observational Studies on Influenza Vaccine Effectiveness
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 WHO Statement on Improving Availability and Transparency of Observational Studies on Influenza
More informationOncologist. The. Commentary
The Oncologist Commentary Commentary: Practicing on the Tip of an Information Iceberg? Evidence of Underpublication of Registered Clinical Trials in Oncology SCOTT RAMSEY, a,b JOHN SCOGGINS c a Fred Hutchinson
More informationEbola Prevention Vaccine Evaluation in Sierra Leone
Ebola Prevention Vaccine Evaluation in Sierra Leone Dr. SAS Kargbo Sierra Leone Ministry of Health and Sanitation Sierra Leone CDC Collaboration World Health Organization, Geneva 9 January 2015 Principal
More informationClinicalTrials.gov Study Record Review
ClinicalTrials.gov Study Record Review Investigator-Initiated Trial (IIT) Registration and Results Reporting Quality Control Checklist for Principal Investigators and Study Managers Adapted with permission
More informationCONSORT 2010 checklist of information to include when reporting a randomised trial*
Supplemental Figures for: Ramosetron Versus Ondansetron in Combination with Aprepitant and Dexamethasone for the Prevention of Highly Emetogenic Chemotherapy-induced Nausea and Vomiting: A Multicenter,
More informationTrial record 1 of 1 for: GO28341 Previous Study Return to List Next Study
1 von 5 11.12.2013 09:04 A service of the U.S. National Institutes of Health Trial record 1 of 1 for: GO28341 Previous Study Return to List Next Study A Study of GDC-0068 in Combination With Fluoropyrimidine
More informationStudy Assessing Deep Molecular Response in Adult Patients With CML in Chronic Phase Treated With Nilotinib Firstline. (NILOdeepR)
We are updating the design of this site. Learn more. Try the new test version at https://clinicaltrials.gov/beta/ Show less Find Studies About Studies Submit Studies Resources About Site Trial record 1
More informationThe Implications of Modifying Study Eligibility Post-Initiation of Recruitment
The Implications of Modifying Study Eligibility Post-Initiation of Recruitment COLLEEN ALLEN, MPH, CCRA THE EMMES CORPORATION THE SOCIETY FOR CLINICAL TRIALS 35 TH ANNUAL MEETING MAY 19, 2014 PHILADELPHIA,
More informationLEGAL ASPECTS of MEDICAL MARIJUANA Florida Nurse Practitioner Network Annual Conference September 17, 2018
LEGAL ASPECTS of MEDICAL MARIJUANA Florida Nurse Practitioner Network Annual Conference September 17, 2018 DISCLAIMER The material presented is general legal information and is not legal advice. Specific
More informationDownloaded from:
Arnup, SJ; Forbes, AB; Kahan, BC; Morgan, KE; McKenzie, JE (2016) The quality of reporting in cluster randomised crossover trials: proposal for reporting items and an assessment of reporting quality. Trials,
More informationGuidance - IDE Early/Expanded Access for Devices
Guidance - IDE Early/Expanded Access for Devices An unapproved medical device may normally only be used on human subjects through an approved clinical study in which the subjects meet certain criteria
More informationWorld Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects
Ethical Principles for Medical Research Involving Human Subjects Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the: 29th WMA General Assembly, Tokyo, Japan, October
More informationNow Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting
A service of the U.S. National Institutes of Health Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting Trial record 1 of 1 for: Keynote 355 Previous Study Return to List
More informationBioimpedance Devices for Detection and Management of Lymphedema
Bioimpedance Devices for Detection and Management of Lymphedema Policy Number: 2.01.82 Last Review: 5/2018 Origination: 1/2011 Next Review: 5/2019 Policy Blue Cross and Blue Shield of Kansas City (Blue
More informationZhengtao Liu 1,2,3*, Shuping Que 4*, Lin Zhou 1,2,3 Author affiliation:
Dose-response Relationship of Serum Uric Acid with Metabolic Syndrome and Non-alcoholic Fatty Liver Disease Incidence: AMeta-analysis of Prospective Studies Zhengtao Liu 1,2,3*, Shuping Que 4*, Lin Zhou
More informationNew NCCIH Funding Opportunities for Natural Product Clinical Trials. May 9, 2017
New NCCIH Funding Opportunities for Natural Product Clinical Trials May 9, 2017 The Webinar will start at 2:00 p.m. All participants have been placed on mute. We will take questions at the end of the presentation
More informationTable S1- PRISMA 2009 Checklist
Table S1- PRISMA 2009 Checklist Section/topic TITLE # Checklist item Title 1 Identify the report as a systematic review, meta-analysis, or both. 1 ABSTRACT Structured summary 2 Provide a structured summary
More informationClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: 10/11/2013. ClinicalTrials.gov ID: NCT
ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: 10/11/2013 ClinicalTrials.gov ID: NCT00168454 Study Identification Unique Protocol ID: 191622-077 Brief Title: A
More informationData Item Definition/Explanation
Please note: This document includes the definitions and explanation of the data items to be completed when submitting a clinical trial for registration on the ANZCTR. The information requested is based
More informationSide 1 af 5. Appendix: Comments on SPIRIT statement:
Side 1 af 5 Appendix: Comments on SPIRIT statement: Checklist: 1. Descriptive title: Study design, population, intervention and trial acronym are stated in the title (The efficacy of ACupuncture On Menopausal
More informationClass II Special Controls Guidance Document: Intraoral Devices for Snoring and/or Obstructive Sleep Apnea; Guidance for Industry and FDA
Class II Special Controls Guidance Document: Intraoral Devices for Snoring and/or Obstructive Sleep Apnea; Guidance for Industry and FDA Document issued on: November 12, 2002 This document supersedes the
More informationOffice of Clinical Research Annual Report 2017 July 1, June 30, 2017
Office of Clinical Research Annual Report 2017 July 1, 2016- June 30, 2017 Table of Contents Title Page Number Mission Statement 1 Objective 1 Research Services 1 Research Highlights 2 Figure 1 Number
More informationCommitted to Environment, Health and Safety
Committed to Environment, Health and Safety Environment, Health and Safety Management System and Policy of GCP Applied Technologies Inc. SEPTEMBER 1, 2017 The GCP Environment, Health, and Safety Management
More informationCenters for Medicare and Medicaid Services. National Coverage of Transcatheter Valve Technologies December 2015
Centers for Medicare and Medicaid Services National Coverage of Transcatheter Valve Technologies December 2015 National Coverage Determination (NCD) for Transcatheter Aortic Valve Replacement (TAVR) (20.32)
More informationNavigating Alliance Protocols
Navigating Alliance Protocols Morgen Alexander-Young, MPH Alliance Central Protocol Operations Program Alliance Spring 2017 Group Meeting Alliance Protocol History Alliance for Clinical Trials in Oncology
More informationProtocol. This trial protocol has been provided by the authors to give readers additional information about their work.
Protocol This trial protocol has been provided by the authors to give readers additional information about their work. Protocol for: Sihvonen R, Paavola M, Malmivaara A, et al. Arthroscopic partial meniscectomy
More informationDissemination experiences from CONSORT and other reporting guidelines
Dissemination experiences from CONSORT and other reporting guidelines Doug Altman Centre for Statistics in Medicine, Oxford EQUATOR Network [Altman and Goodman, JAMA 1994] 2 Passive
More informationStandards for the reporting of new Cochrane Intervention Reviews
Methodological Expectations of Cochrane Intervention Reviews (MECIR) Standards for the reporting of new Cochrane Intervention Reviews 24 September 2012 Preface The standards below summarize proposed attributes
More informationCMS EHR Incentive Program: Proposed Rules for Stage 2 and Stage 3 Meaningful Use Focus on Eligible Hospitals
CMS EHR Incentive Program: Proposed Rules for Stage 2 and Stage 3 Meaningful Use Focus on Eligible Hospitals April 28, 2015 Hosted by: Sponsored by: Today s Event Sponsored By One of the nation s largest
More informationRobert M. Jacobson, M.D. Department of Pediatric and Adolescent Medicine Mayo Clinic, Rochester, Minnesota
How to Conduct a Systematic Review: A Workshop 24 th Annual Primary Care Research Methods & Statistics Conference, San Antonio, Texas Saturday, December 3, 2011 Robert M. Jacobson, M.D. Department of Pediatric
More informationRisk Evaluation And Mitigation Strategies:
Risk Evaluation And Mitigation Strategies: The Experts Answer Questions from Health-System Pharmacists A midday symposium about the risk evaluation and mitigation strategies (REMS) required by the Food
More informationClinicalTrials.gov "Basic Results" Data Element Definitions (DRAFT)
ClinicalTrials.gov "Basic Results" Data Element Definitions (DRAFT) January 9, 2009 * Required by ClinicalTrials.gov [*] Conditionally required by ClinicalTrials.gov (FDAAA) May be required to comply with
More informationNew NCCIH Funding Opportunities for Mind and Body Clinical Trials. April 24, 2017
New NCCIH Funding Opportunities for Mind and Body Clinical Trials April 24, 2017 Introductions Wendy Weber, N.D., Ph.D., M.P.H. Branch Chief, Clinical Research in Complementary and Integrative Health Branch,
More informationROLE OF PRMS FROM START TO FINISH. Tricia Adrales Bentz, MHA Hollings Cancer Center
ROLE OF PRMS FROM START TO FINISH Tricia Adrales Bentz, MHA Hollings Cancer Center National Cancer Institute Designation MUSC-HCC received its NCI designation in 2009. The only NCI designated cancer center
More informationGarbage in - garbage out? Impact of poor reporting on the development of systematic reviews
Garbage in - garbage out? Impact of poor reporting on the development of systematic reviews ACT now: EQUATOR Scientific Symposium Freiburg, 11 October 2012 Erik von Elm, MD MSc FMH Cochrane Switzerland
More informationInstitutional Review Board (IRB) at SMU. Dr. Maribeth Kuenzi, Chair Ms. Shannon Lunt, SMU Director of Research Compliance
Institutional Review Board (IRB) at SMU Dr. Maribeth Kuenzi, Chair Ms. Shannon Lunt, SMU Director of Research Compliance slunt@smu.edu 214.768.2029 Permission granted 11/24/14 What does the IRB review?
More informationUse of Standards in Substantial Equivalence Determinations
Guidance for Industry and for FDA Staff Use of Standards in Substantial Equivalence Determinations Document issued on: March 12, 2000 U.S. Department Of Health And Human Services Food and Drug Administration
More informationComplementary and Alternative Medicine in Treating Autism Spectrum Disorders. Request for Applications
Complementary and Alternative Medicine in Treating Autism Spectrum Disorders Request for Applications Introduction Although medical care in the United States is increasingly driven by evidence-based practice,
More informationQuality of Life of HIV-infected Patients Study
Investigator Name: Quality of Life of HIV-infected Patients Study OptumInsight is seeking for additional investigators for a multicenter longitudinal observational study involving adult patients with HIV.
More informationEnvironmental, Health and Safety
Environmental, Health and Safety Codes of Practice The Environmental, Health and Safety (EHS) Codes of Practice set forth Zimmer EHS requirements for our business functions and facilities worldwide. In
More informationCommon Data Elements: Making the Mass of NIH Measures More Useful
Common Data Elements WG Common Data Elements: Making the Mass of NIH Measures More Useful Jerry Sheehan Assistant Director for Policy Development Na?onal Library of Medicine Gene/c Alliance Webinar Series
More informationSKCC Protocol Review Committee New Study Application
Instructions: Submit the following documents to prc@jefferson.edu - Completed New Study Application (aka MCSF) - Protocol - Protocol Facilitation Committee Approval (if applicable) - MDG Priority Score
More informationUses and misuses of the STROBE statement: bibliographic study
Uses and misuses of the STROBE statement: bibliographic study Bruno R. da Costa 1, Myriam Cevallos 1, 2, Douglas G. Altman 3, Anne W.S. Rutjes 1, Matthias Egger 1 1. Institute of Social & Preventive Medicine
More informationStudying First Line Treatment of Chronic Myeloid Leukemia (CML) in a Real-world Setting (SIMPLICITY)
A service of the U.S. National Institutes of Health Studying First Line Treatment of Chronic Myeloid Leukemia (CML) in a Real-world Setting (SIMPLICITY) This study is currently recruiting participants.
More informationTransparency and accuracy in reporting health research
Transparency and accuracy in reporting health research Doug Altman The EQUATOR Network Centre for Statistics in Medicine, Oxford, UK Transparency and value Research only has value if Study methods have
More informationStudy Endpoint Considerations: Final PRO Guidance and Beyond
Study Endpoint Considerations: Final PRO Guidance and Beyond Laurie Burke Associate Director for Study Endpoints and Labeling OND/CDER/FDA Presented at: FIRST ANNUAL PATIENT REPORTED OUTCOMES (PRO) CONSORTIUM
More informationHuman Research Protection Program Institutional Review Board Procedure
Page 1 of 10 DESCRIPTION INSTITUTIONAL REVIEW BOARD REVIEW OF RESEARCH INVOLVING PRISONERS Prisoners may be under constraints because of their incarceration that could affect their ability to make a truly
More informationOverview of the Legal Framework for Medical Device Regulation in the United States
1 Overview of the Legal Framework for Medical Device Regulation in the United States Ellen J. Flannery This chapter provides an overview of the legal framework for medical device regulation in the United
More informationInvestigator Initiated Study Proposal Form
Please submit completed form to IISReview@KCI1.com Date Submitted Name & Title Institution Address Phone Number Email Address Principal Investigator / Institution YES NO Multi Center Study Acelity Product(s)
More informationComplete Central Registry Treatment Information Requires Ongoing Reporting and Consolidation Well Beyond 6-Month Reporting
Complete Central Registry Treatment Information Requires Ongoing Reporting and Consolidation Well Beyond 6-Month Reporting Eric B. Durbin, DrPH, MS, Director of Cancer Informatics Frances E. Ross, CTR,
More informationIRB Review Points to Consider September 2016
POINTS TO CONSIDER Principal investigators 1. Does the principal investigator have the appropriate qualifications, experience, and facilities to ensure that all aspects of the project and follow-up will
More informationNonallergic Rhinitis: Developing Drug Products for Treatment Guidance for Industry
Nonallergic Rhinitis: Developing Drug Products for Treatment Guidance for Industry DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding
More informationI, Mary M. Langman, Director, Information Issues and Policy, Medical Library Association
I, Mary M. Langman, Director, Information Issues and Policy, Medical Library Association (MLA), submit this statement on behalf of MLA and the Association of Academic Health Sciences Libraries (AAHSL).
More informationAccepted refereed manuscript of:
Accepted refereed manuscript of: Zwarenstein M, Treweek S & Loudon K (2017) PRECIS-2 helps researchers design more applicable RCTs while CONSORT Extension for Pragmatic Trials helps knowledge users decide
More informationDisclaimer. The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be
Ending the Myths: Best Practice in Trial Conduct in Latin America Katie Margules Global Vice President Alliance Management Covance Disclaimer The views and opinions expressed in the following PowerPoint
More informationAmerican Journal of Internal Medicine
American Journal of Internal Medicine 2016; 4(3): 49-59 http://www.sciencepublishinggroup.com/j/ajim doi: 10.11648/j.ajim.20160403.12 ISSN: 2330-4316 (Print); ISSN: 2330-4324 (Online) The Effect of Dose-Reduced
More informationLearning from Systematic Review and Meta analysis
Learning from Systematic Review and Meta analysis Efficacy and Safety of Antiscabietic Agents: A Systematic Review and Network Meta analysis of Randomized Controlled Trials KUNLAWAT THADANIPON, MD 4 TH
More informationClinical Study Design: From Pilot to Randomized Controlled Trials
Clinical Study Design: From Pilot to Randomized Controlled Trials Thomas C. Hulsey, MSPH, Sc.D. Professor and Chair, Department of Epidemiology Director, Clinical Research Education, CTSI What is a clinical
More informationGuidance for Industry
Reprinted from FDA s website by Guidance for Industry E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs Questions and Answers (R1) U.S. Department
More informationAssessing the Safety of Vaccines at the FDA: Pre- and Post-Licensure Evaluation
Assessing the Safety of Vaccines at the FDA: Pre- and Post-Licensure Evaluation Karen Farizo, M.D. Office of Vaccines Research and Review Center for Biologics Evaluation and Research US Food and Drug Administration
More informationA service of the U.S. National Institutes of Health Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting
A service of the U.S. National Institutes of Health w Available: Final Rule for FDAAA 81 and NIH Policy on Clinical Trial Reporting Trial record 1 of 1 for: FENHYDPAI414 Previous Study Return to List Next
More informationIRB for Humanists. Naomi E. Coll, MPH, CPH, CIP Manager of Research Integrity
IRB for Humanists Naomi E. Coll, MPH, CPH, CIP Manager of Research Integrity Grace Caskie, Ph.D. Associate Professor Counseling Psychology IRB co-chair Patti Manz, Ph.D. Associate Professor School Psychology
More informationComplete Summary GUIDELINE TITLE
Complete Summary GUIDELINE TITLE Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.
More information