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Trials Jul 2020Clinicians, patients, and policy-makers rely on published evidence from clinical trials to help inform decision-making. A lack of complete and transparent reporting of... (Review)
Review
BACKGROUND
Clinicians, patients, and policy-makers rely on published evidence from clinical trials to help inform decision-making. A lack of complete and transparent reporting of the investigated trial outcomes limits reproducibility of results and knowledge synthesis efforts, and contributes to outcome switching and other reporting biases. Outcome-specific extensions for the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT-Outcomes) and Consolidated Standards of Reporting Trials (CONSORT-Outcomes) reporting guidelines are under development to facilitate harmonized reporting of outcomes in trial protocols and reports. The aim of this review was to identify and synthesize existing guidance for trial outcome reporting to inform extension development.
METHODS
We searched for documents published in the last 10 years that provided guidance on trial outcome reporting using: an electronic bibliographic database search (MEDLINE and the Cochrane Methodology Register); a grey literature search; and solicitation of colleagues using a snowballing approach. Two reviewers completed title and abstract screening, full-text screening, and data charting after training. Extracted trial outcome reporting guidance was compared with candidate reporting items to support, refute, or refine the items and to assess the need for the development of additional items.
RESULTS
In total, 1758 trial outcome reporting recommendations were identified within 244 eligible documents. The majority of documents were published by academic journals (72%). Comparison of each recommendation with the initial list of 70 candidate items led to the development of an additional 62 items, producing 132 candidate items. The items encompassed outcome selection, definition, measurement, analysis, interpretation, and reporting of modifications between trial documents. The total number of documents supporting each candidate item ranged widely (median 5, range 0-84 documents per item), illustrating heterogeneity in the recommendations currently available for outcome reporting across a large and diverse sample of sources.
CONCLUSIONS
Outcome reporting guidance for clinical trial protocols and reports lacks consistency and is spread across a large number of sources that may be challenging to access and implement in practice. Evidence and consensus-based guidance, currently in development (SPIRIT-Outcomes and CONSORT-Outcomes), may help authors adequately describe trial outcomes in protocols and reports transparently and completely to help reduce avoidable research waste.
Topics: Clinical Trials as Topic; Consensus; Endpoint Determination; Humans; Information Dissemination; Research Design; Treatment Outcome
PubMed: 32641085
DOI: 10.1186/s13063-020-04440-w -
Seminars in Arthritis and Rheumatism Dec 2019In the last two decades drug trials in ankylosing spondylitis (AS) have been extremely successful and many effective new drugs have been approved for the treatment of... (Review)
Review
In the last two decades drug trials in ankylosing spondylitis (AS) have been extremely successful and many effective new drugs have been approved for the treatment of patients with AS. In 2009, new classification criteria for axial spondyloarthritis (axSpA) have been released that capture not only AS, but also patients with presumably earlier non-radiographic axSpA. These criteria have served as inclusion criteria for patients to be enrolled in drug trials for the indication of nr-axSpA. The theme to be discussed in this article pertains to changes in the design of clinical trials required to optimize the process of drug-testing and -approval in a changed environment. Additional treatment criteria (MRI-and CRP-positivity), better response measurement (ASDAS) and trial homogeneity will be addressed against the background of the expansion of the disease spectrum of axSpA which has been the consequence of the new classification criteria for axSpA.
Topics: Antirheumatic Agents; Clinical Trials as Topic; Diagnostic Imaging; Humans; Spondylarthritis
PubMed: 31779854
DOI: 10.1016/j.semarthrit.2019.09.016 -
Tomography (Ann Arbor, Mich.) Jun 2020The Clinical Trial Design and Development Working Group within the Quantitative Imaging Network focuses on providing support for the development, validation, and... (Review)
Review
The Clinical Trial Design and Development Working Group within the Quantitative Imaging Network focuses on providing support for the development, validation, and harmonization of quantitative imaging (QI) methods and tools for use in cancer clinical trials. In the past 10 years, the Group has been working in several areas to identify challenges and opportunities in clinical trials involving QI and radiation oncology. The Group has been working with Quantitative Imaging Network members and the Quantitative Imaging Biomarkers Alliance leadership to develop guidelines for standardizing the reporting of quantitative imaging. As a validation platform, the Group led a multireader study to test a semi-automated positron emission tomography quantification software. Clinical translation of QI tools cannot be possible without a continuing dialogue with clinical users. This article also highlights the outreach activities extended to cooperative groups and other organizations that promote the use of QI tools to support clinical decisions.
Topics: Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Diagnostic Imaging; Humans; Neoplasms; Positron-Emission Tomography; Radiation Oncology; Randomized Controlled Trials as Topic; Tomography, X-Ray Computed
PubMed: 32548281
DOI: 10.18383/j.tom.2019.00022 -
Hepatology (Baltimore, Md.) Jul 2014The diagnostic research process can be divided into five phases, designed to establish the clinical utility of a new diagnostic test--the index test. The aim of the... (Review)
Review
UNLABELLED
The diagnostic research process can be divided into five phases, designed to establish the clinical utility of a new diagnostic test--the index test. The aim of the present review is to illustrate the study designs that are appropriate for each diagnostic phase, using clinical examples regarding liver fibrosis diagnosed with transient elastography, when possible. Phase 0 is the preclinical pilot phase during which the validity, reliability, and reproducibility of the index test are assessed in healthy and diseased people. Phase I is designed to describe the distribution of the index test results in healthy people and its normal values. Phase IIA comprises studies designed to estimate the accuracy (sensitivity and specificity) of the index test in discriminating between diseased and nondiseased people in a clinically relevant population. Phase IIB studies allow the comparison of the accuracy of different index tests; Phase IIC studies aim to evaluate the possible harms of incorporating the index test in a diagnostic-therapeutic strategy. In phase III, diagnostic test-therapeutic randomized clinical trials aim to assess the benefits and harms of the new diagnostic-therapeutic strategy versus the present strategy. Phase IV comprises large surveillance cohort studies that aim to assess the effectiveness of the new diagnostic-therapeutic strategy in clinical practice.
CONCLUSION
As common in clinical research, giving excessive weight to the results of single studies and trials is likely to divert from the totality of evidence obtained through the systematic reviews of these studies, conducted with rigorous methodology and statistical methods. (Hepatology 2014;60:408-418).
Topics: Animals; Clinical Trials as Topic; Data Interpretation, Statistical; Elasticity Imaging Techniques; Gastroenterology; Humans; Liver Diseases; Translational Research, Biomedical
PubMed: 24277656
DOI: 10.1002/hep.26948 -
Clinical Cancer Research : An Official... May 2021Performance status (PS) is one of the most common eligibility criteria. Many trials are limited to patients with high-functioning PS, resulting in important differences... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Performance status (PS) is one of the most common eligibility criteria. Many trials are limited to patients with high-functioning PS, resulting in important differences between trial participants and patient populations with the disease. In addition, existing PS measures are subjective and susceptible to investigator bias.
EXPERIMENTAL DESIGN
A multidisciplinary working group of the American Society of Clinical Oncology and Friends of Cancer Research evaluated how PS eligibility criteria could be more inclusive. The working group recommendations are based on a literature search, review of trials, simulation study, and multistakeholder consensus. The working group prioritized inclusiveness and access to investigational therapies, while balancing patient safety and study integrity.
RESULTS
Broadening PS eligibility criteria may increase the number of potentially eligible patients for a given clinical trial, thus shortening accrual time. It may also result in greater participant diversity, potentially reduce trial participant and patient disparities, and enable clinicians to more readily translate trial results to patients with low-functioning PS. Potential impact on outcomes was explored through a simulation trial demonstrating that when the number of Eastern Cooperative Oncology Group PS2 participants was relatively small, the effect on the estimated HR and power was modest, even when PS2 patients did not derive a treatment benefit.
CONCLUSIONS
Expanding PS eligibility criteria to be more inclusive may be justified in many cases and could result in faster accrual rates and more representative trial populations..
Topics: Biomedical Research; Clinical Decision-Making; Clinical Trials as Topic; Disease Management; Humans; Medical Oncology; Neoplasms; Research Design
PubMed: 33563633
DOI: 10.1158/1078-0432.CCR-20-3868 -
BMJ Open Jul 2022Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected...
INTRODUCTION
Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected countries. This study aims to evaluate the impact of enhanced case detection using molecular testing called loop-mediated isothermal amplification (LAMP) on birth outcomes in a prospective study design.
METHODS AND ANALYSIS
A pragmatic randomised diagnostic outcomes trial will be conducted in several health institutes in different Ethiopian regions. Women (n=2583) in their first and second trimesters of pregnancy will be included in the study and individually randomised to the standard of care or enhanced case detection arms, and followed until delivery. Enrolment will encompass the malaria peak transmission seasons. In the standard of care arm, a venous blood sample will be collected for malaria diagnosis only in symptomatic patients. In contrast, in the intervention arm, mothers will be tested by a commercially available Conformité Européene (CE)-approved LAMP malaria test, microscopy and rapid diagnostic test for malaria regardless of their symptoms at each antenatal care visit. The primary outcome of the study is to measure birth weight.
ETHICS AND DISSEMINATION
The study was approved by the following ethical research boards: Armauer Hansen Research Institute/ALERT Ethics Review Committee (FORM AF-10-015.1, Protocol number PO/05/20), the Ethiopia Ministry of Science and Higher Education National Research Ethics Review Committee (approval SRA/11.7/7115/20), the Ethiopia Food and Drug Administration (approval 02/25/33/I), UCalgary Conjoint Health Research Ethics Board (REB21-0234). The study results will be shared with the institutions and stakeholders such as the Ethiopia Ministry of Health, the Foundation for Innovative Diagnostics, WHO's Multilateral initiative on Malaria - Tropical Diseases Research (TDR-MIM), Roll Back Malaria and the Malaria in Pregnancy Consortium. The study results will also be published in peer-reviewed journals and presented at international conferences.
TRIAL REGISTRATION NUMBER
NCT03754322.
Topics: Female; Humans; Malaria; Mass Screening; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Pragmatic Clinical Trials as Topic; Pregnancy; Pregnancy Complications, Parasitic; Prospective Studies; Randomized Controlled Trials as Topic; Technology
PubMed: 35851027
DOI: 10.1136/bmjopen-2021-058397 -
Clinical Cancer Research : An Official... May 2021In clinical research, eligibility criteria promote patient safety and optimize the evidence generated from clinical trials. However, overly stringent eligibility... (Review)
Review
PURPOSE
In clinical research, eligibility criteria promote patient safety and optimize the evidence generated from clinical trials. However, overly stringent eligibility criteria, including laboratory requirements, may limit enrollment, resulting in delayed trial completion and potentially limiting applicability of trial results to a general practice population.
EXPERIMENTAL DESIGN
Starting in 2018, a working group consisting of experts in direct patient care, the FDA, industry, and patient advocacy developed recommendations to guide the optimal use of laboratory reference ranges and testing intervals in clinical trial eligibility criteria and study procedures. The working group evaluated current eligibility criteria across different clinical trial phases and performed a literature review to evaluate the impact of and justification for laboratory test eligibility requirements and testing intervals in clinical trials. Recommendations were developed on the basis of the goals of promoting safety and optimizing the evidence generated, while also expanding eligibility and applicability, and minimizing excess burden of trial participation.
RESULTS
In general, we found little variation over time and trial phase in laboratory test requirements, suggesting that these eligibility criteria are not refined according to ongoing clinical experience. We propose recommendations to optimize the use of laboratory tests when considering eligibility criteria.
CONCLUSIONS
Tailoring the use of laboratory test requirements and testing intervals may increase the number and diversity of patients in clinical trials and provide clinical data that more closely represent the general practice populations..
Topics: Biomedical Research; Clinical Decision-Making; Clinical Trials as Topic; Disease Management; Humans; Medical Oncology; Neoplasms; Research Design
PubMed: 33563636
DOI: 10.1158/1078-0432.CCR-20-3853 -
Circulation Dec 2015
Review
Topics: Clinical Trials as Topic; Diagnostic Imaging; Endpoint Determination; Exercise Test; Humans; Hypertension, Pulmonary; Risk Assessment
PubMed: 26621638
DOI: 10.1161/CIRCULATIONAHA.114.012328 -
Frontiers of Neurology and Neuroscience 2009
Topics: Clinical Trials as Topic; Research Design; Treatment Outcome
PubMed: 19478503
DOI: 10.1159/000209481 -
BMJ Evidence-based Medicine Aug 2020High-quality research demonstrating a lack of effectiveness may facilitate the 'de-adoption' of ineffective health services. However, there has been little debate on the...
High-quality research demonstrating a lack of effectiveness may facilitate the 'de-adoption' of ineffective health services. However, there has been little debate on the optimal design for ineffectiveness research-studies exploring the research hypothesis that an intervention is ineffective. The aim of this study was to explore investigators' preferences for trial design for ineffectiveness research. We conducted a mixed-methods online survey with principle investigators identified from clinicaltrials.gov. A vignette described researchers planning a trial to test a widely used intervention they hypothesised was ineffective. One multiple-choice question asked whether a superiority trial or equivalence trial design was favoured, and one free-response question asked about the reasons for that choice. Free-response answers were analysed using content analysis to identify related reasons. 139 participants completed the survey (completion rate 37.5%). Overall, 56.8% favoured superiority trials, 27.3% favoured equivalence trials and 15.8% were unsure. Reasons identified for favouring superiority trials were: (1) evidence of superiority should be required to justify active treatment, (2) superiority trials are more familiar, (3) placebo should not be the comparator in equivalence trials and (4) superiority trials require smaller sample sizes. Reasons identified for favouring equivalence trials were: (1) negative superiority trials represent a lack of evidence of effectiveness, not evidence of ineffectiveness and (2) the research hypothesis should not be the same as the null hypothesis. A minority of experienced researchers favour equivalence trials for ineffectiveness research, and misconceptions and lack of familiarity with equivalence trials may be contributing factors.
Topics: Attitude of Health Personnel; Clinical Trials as Topic; Equivalence Trials as Topic; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Research Design; Surveys and Questionnaires; Treatment Outcome
PubMed: 31757840
DOI: 10.1136/bmjebm-2019-111276