Discrepancies in endpoints between clinical trial protocols and clinical trial registration in randomized trials in oncology

Victoria J. Serpas; Kanwal P. Raghav; Daniel M. Halperin; James Yao; Michael J. Overman

doi:10.1186/s12874-018-0627-2

Discrepancies in endpoints between clinical trial protocols and clinical trial registration in randomized trials in oncology

Victoria J. Serpas, Kanwal P. Raghav, Daniel M. Halperin, James Yao, Michael J. Overman

GI Medical Oncology

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Background: Clinical trials are an essential part of evidence-based medicine. Hence, to ensure transparency and accountability in these clinical trials, policies for registration have been framed with emphasis on mandatory submission of trial elements, specifically outcome measures. As these efforts evolve further, we sought to evaluate the current status of endpoint reporting in clinical trial registries. Methods: We reviewed 71 oncology related randomized controlled trials published in three high impact journals. We compared primary (PEP) and non-primary endpoints (NPEP) between the clinical trial protocols of these trials and their corresponding registration in one of the 14 primary global clinical trial registries. A discrepancy was defined as the non-reporting or absence of an endpoint in either the protocol or registry. The primary endpoint was the rate of discrepancy between secondary endpoints in clinical trial protocols and clinical trial registries. Results: Of the 71 clinical trials, a discrepancy in PEP was found in only 4 trials (6%). Secondary endpoint (SEP) differences were found in 45 (63%) trials. Among these 45 trials, 36 (80%) had SEPs that were planned in the protocol but not reported in the registry and 19 (42%) had SEPs with endpoints in the registry that were not found in the protocol. The total number of SEPs that were absent from the corresponding registry and protocol were 84 and 29, respectively. Of these endpoints, 48 (57%) and 9 (31%) were included in the published report of these trials. Conclusion: Although recent regulations and enhanced procedures have improved the number and quality of clinical trial registrations, inconsistencies regarding endpoint reporting still exist. Though further guidelines for the registration of clinical trials will help, greater efforts to provide a correct, easily accessible, and complete representation of planned endpoints are needed.

Original language	English (US)
Article number	169
Journal	BMC Medical Research Methodology
Volume	18
Issue number	1
DOIs	https://doi.org/10.1186/s12874-018-0627-2
State	Published - Dec 12 2018

Keywords

Endpoints
Registry
Reporting

ASJC Scopus subject areas

Epidemiology
Health Informatics

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10.1186/s12874-018-0627-2

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title = "Discrepancies in endpoints between clinical trial protocols and clinical trial registration in randomized trials in oncology",

abstract = "Background: Clinical trials are an essential part of evidence-based medicine. Hence, to ensure transparency and accountability in these clinical trials, policies for registration have been framed with emphasis on mandatory submission of trial elements, specifically outcome measures. As these efforts evolve further, we sought to evaluate the current status of endpoint reporting in clinical trial registries. Methods: We reviewed 71 oncology related randomized controlled trials published in three high impact journals. We compared primary (PEP) and non-primary endpoints (NPEP) between the clinical trial protocols of these trials and their corresponding registration in one of the 14 primary global clinical trial registries. A discrepancy was defined as the non-reporting or absence of an endpoint in either the protocol or registry. The primary endpoint was the rate of discrepancy between secondary endpoints in clinical trial protocols and clinical trial registries. Results: Of the 71 clinical trials, a discrepancy in PEP was found in only 4 trials (6%). Secondary endpoint (SEP) differences were found in 45 (63%) trials. Among these 45 trials, 36 (80%) had SEPs that were planned in the protocol but not reported in the registry and 19 (42%) had SEPs with endpoints in the registry that were not found in the protocol. The total number of SEPs that were absent from the corresponding registry and protocol were 84 and 29, respectively. Of these endpoints, 48 (57%) and 9 (31%) were included in the published report of these trials. Conclusion: Although recent regulations and enhanced procedures have improved the number and quality of clinical trial registrations, inconsistencies regarding endpoint reporting still exist. Though further guidelines for the registration of clinical trials will help, greater efforts to provide a correct, easily accessible, and complete representation of planned endpoints are needed.",

keywords = "Endpoints, Registry, Reporting",

author = "Serpas, {Victoria J.} and Raghav, {Kanwal P.} and Halperin, {Daniel M.} and James Yao and Overman, {Michael J.}",

note = "Funding Information: The first U.S. federal law to require clinical trial registration was the US Food and Drug Administration (FDA) Modernization Act of 1997 [1]. Following this, in 2000, the public access online clinical trial registry, clini-caltrials.gov, was created by the National Institutes of Health (NIH) [2]. In the years following, many other groups including the International Committee of Medical Journal Editors (ICMJE), the World Health Organization (WHO), and the World Medical Association created Funding Information: CORRE: Comprehensive outcomes reporting in randomized evidence; FDA: U.S. Food and Drug Administration; ICMJE: International Committee of Medical Journal Editors; JCO: Journal of Clinical Oncology; NEJM: New England Journal of Medicine; NIH: National Institutes of Health; NPEP: Non-primary endpoint; PEP: Primary endpoint; PFS: Progression free survival; RCT: Randomized controlled trials; SAP: Statistical analysis plan; SEP: Secondary endpoint; TTP: Time to progression; WHO: World Health Organization Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "12",

doi = "10.1186/s12874-018-0627-2",

language = "English (US)",

volume = "18",

journal = "BMC Medical Research Methodology",

issn = "1471-2288",

publisher = "BioMed Central",

number = "1",

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T1 - Discrepancies in endpoints between clinical trial protocols and clinical trial registration in randomized trials in oncology

AU - Serpas, Victoria J.

AU - Raghav, Kanwal P.

AU - Halperin, Daniel M.

AU - Yao, James

AU - Overman, Michael J.

N1 - Funding Information: The first U.S. federal law to require clinical trial registration was the US Food and Drug Administration (FDA) Modernization Act of 1997 [1]. Following this, in 2000, the public access online clinical trial registry, clini-caltrials.gov, was created by the National Institutes of Health (NIH) [2]. In the years following, many other groups including the International Committee of Medical Journal Editors (ICMJE), the World Health Organization (WHO), and the World Medical Association created Funding Information: CORRE: Comprehensive outcomes reporting in randomized evidence; FDA: U.S. Food and Drug Administration; ICMJE: International Committee of Medical Journal Editors; JCO: Journal of Clinical Oncology; NEJM: New England Journal of Medicine; NIH: National Institutes of Health; NPEP: Non-primary endpoint; PEP: Primary endpoint; PFS: Progression free survival; RCT: Randomized controlled trials; SAP: Statistical analysis plan; SEP: Secondary endpoint; TTP: Time to progression; WHO: World Health Organization Publisher Copyright: © 2018 The Author(s).

PY - 2018/12/12

Y1 - 2018/12/12

N2 - Background: Clinical trials are an essential part of evidence-based medicine. Hence, to ensure transparency and accountability in these clinical trials, policies for registration have been framed with emphasis on mandatory submission of trial elements, specifically outcome measures. As these efforts evolve further, we sought to evaluate the current status of endpoint reporting in clinical trial registries. Methods: We reviewed 71 oncology related randomized controlled trials published in three high impact journals. We compared primary (PEP) and non-primary endpoints (NPEP) between the clinical trial protocols of these trials and their corresponding registration in one of the 14 primary global clinical trial registries. A discrepancy was defined as the non-reporting or absence of an endpoint in either the protocol or registry. The primary endpoint was the rate of discrepancy between secondary endpoints in clinical trial protocols and clinical trial registries. Results: Of the 71 clinical trials, a discrepancy in PEP was found in only 4 trials (6%). Secondary endpoint (SEP) differences were found in 45 (63%) trials. Among these 45 trials, 36 (80%) had SEPs that were planned in the protocol but not reported in the registry and 19 (42%) had SEPs with endpoints in the registry that were not found in the protocol. The total number of SEPs that were absent from the corresponding registry and protocol were 84 and 29, respectively. Of these endpoints, 48 (57%) and 9 (31%) were included in the published report of these trials. Conclusion: Although recent regulations and enhanced procedures have improved the number and quality of clinical trial registrations, inconsistencies regarding endpoint reporting still exist. Though further guidelines for the registration of clinical trials will help, greater efforts to provide a correct, easily accessible, and complete representation of planned endpoints are needed.

AB - Background: Clinical trials are an essential part of evidence-based medicine. Hence, to ensure transparency and accountability in these clinical trials, policies for registration have been framed with emphasis on mandatory submission of trial elements, specifically outcome measures. As these efforts evolve further, we sought to evaluate the current status of endpoint reporting in clinical trial registries. Methods: We reviewed 71 oncology related randomized controlled trials published in three high impact journals. We compared primary (PEP) and non-primary endpoints (NPEP) between the clinical trial protocols of these trials and their corresponding registration in one of the 14 primary global clinical trial registries. A discrepancy was defined as the non-reporting or absence of an endpoint in either the protocol or registry. The primary endpoint was the rate of discrepancy between secondary endpoints in clinical trial protocols and clinical trial registries. Results: Of the 71 clinical trials, a discrepancy in PEP was found in only 4 trials (6%). Secondary endpoint (SEP) differences were found in 45 (63%) trials. Among these 45 trials, 36 (80%) had SEPs that were planned in the protocol but not reported in the registry and 19 (42%) had SEPs with endpoints in the registry that were not found in the protocol. The total number of SEPs that were absent from the corresponding registry and protocol were 84 and 29, respectively. Of these endpoints, 48 (57%) and 9 (31%) were included in the published report of these trials. Conclusion: Although recent regulations and enhanced procedures have improved the number and quality of clinical trial registrations, inconsistencies regarding endpoint reporting still exist. Though further guidelines for the registration of clinical trials will help, greater efforts to provide a correct, easily accessible, and complete representation of planned endpoints are needed.

KW - Endpoints

KW - Registry

KW - Reporting

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Discrepancies in endpoints between clinical trial protocols and clinical trial registration in randomized trials in oncology

Abstract

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