Authors: An-Wen Chan, Jennifer M Tetzlaff, Douglas G Altman...

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

Topics: Checklist; Clinical Protocols; Clinical Trials as Topic; Humans

PubMed: 23295957
DOI: 10.7326/0003-4819-158-3-201302050-00583

Review

Authors: Craig A Umscheid, David J Margolis, Craig E Grossman...

The recent focus of federal funding on comparative effectiveness research underscores the importance of clinical trials in the practice of evidence-based medicine and health care reform. The impact of clinical trials not only extends to the individual patient by establishing a broader selection of effective therapies, but also to society as a whole by enhancing the value of health care provided. However, clinical trials also have the potential to pose unknown risks to their participants, and biased knowledge extracted from flawed clinical trials may lead to the inadvertent harm of patients. Although conducting a well-designed clinical trial may appear straightforward, it is founded on rigorous methodology and oversight governed by key ethical principles. In this review, we provide an overview of the ethical foundations of trial design, trial oversight, and the process of obtaining approval of a therapeutic, from its pre-clinical phase to post-marketing surveillance. This narrative review is based on a course in clinical trials developed by one of the authors (DJM), and is supplemented by a PubMed search predating January 2011 using the keywords "randomized controlled trial," "patient/clinical research," "ethics," "phase IV," "data and safety monitoring board," and "surrogate endpoint." With an understanding of the key principles in designing and implementing clinical trials, health care providers can partner with the pharmaceutical industry and regulatory bodies to effectively compare medical therapies and thereby meet one of the essential goals of health care reform.

Topics: Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Clinical Trials, Phase IV as Topic; Drug Evaluation; Humans; Randomized Controlled Trials as Topic; United States

PubMed: 21904102
DOI: 10.3810/pgm.2011.09.2475

Review

Authors: Deepak L Bhatt, Cyrus Mehta

Topics: Biomarkers; Clinical Trials as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Government Regulation; Humans; Research Design; Sample Size

PubMed: 27406349
DOI: 10.1056/NEJMra1510061

Authors: Paul Myles, Jessica Kasza, Tari Turner...

Topics: Clinical Trials as Topic; Data Interpretation, Statistical; Humans; Meta-Analysis as Topic

PubMed: 33992396
DOI: 10.1016/j.bja.2021.04.007

Authors: Laura Flight, Steven A Julious

A sample size justification is a vital part of any trial design. However, estimating the number of participants required to give a meaningful result is not always straightforward. A number of components are required to facilitate a suitable sample size calculation. In this paper, the steps for conducting sample size calculations for non-inferiority and equivalence trials are summarised. Practical advice and examples are provided that illustrate how to carry out the calculations by hand and using the app SampSize.

Topics: Clinical Trials as Topic; Humans; Sample Size; Therapeutic Equivalency

PubMed: 26604186
DOI: 10.1002/pst.1716

Review

Authors: Juliet K Knowles, Aaron E L Warren, Ismail S Mohamed...

OBJECTIVE

Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy that is typically refractory to treatment. We surveyed the current landscape of LGS treatment, aiming to identify challenges to the development of efficacious therapies, and to articulate corresponding priorities toward clinical trials that improve outcomes.

METHODS

The LGS Special Interest Group of the Pediatric Epilepsy Research Consortium integrated evidence from the literature and expert opinion, into a narrative review.

RESULTS

We provide an overview of approved and emerging medical, dietary, surgical and neuromodulation approaches for LGS. We note that quality of care could be improved by standardizing LGS treatment based on expert consensus and empirical data. Whereas LGS natural history is incompletely understood, prospective studies and use of large retrospective datasets to understand LGS across the lifespan would enable clinical trials that address these dynamics. Recent discoveries related to LGS pathophysiology should enable development of disease-modifying therapies, which are currently lacking. Finally, clinical trials have focused chiefly on seizures involving "drops," but should incorporate additional patient-centered outcomes, using emerging measures adapted to people with LGS.

INTERPRETATION

Clinicians and researchers should enact these priorities, with the goal of patient-centered clinical trials that are tailored to LGS pathophysiology and natural history.

Topics: Humans; Lennox Gastaut Syndrome; Clinical Trials as Topic

PubMed: 39440617
DOI: 10.1002/acn3.52211

Authors: Christina L Roland, Elizabeth G Grubbs, Matthew H G Katz...

Topics: Clinical Trials as Topic; Cooperative Behavior; Curriculum; Education, Medical, Graduate; Fellowships and Scholarships; Humans; Interprofessional Relations; Research Design; Surgical Oncology; Texas

PubMed: 32149390
DOI: 10.1002/jso.25889

Authors: Luigia Scudeller, Angela Huttner, Mical Paul...

Topics: Clinical Trials as Topic; Communicable Diseases; Humans; Microbiology; Publishing; Research; Time Factors

PubMed: 33421571
DOI: 10.1016/j.cmi.2020.12.034

Authors: Robert M Califf, Jeremy Sugarman

The need for high-quality evidence to support decision making about health and health care by patients, physicians, care providers, and policy-makers is well documented. However, serious shortcomings in evidence persist. Pragmatic clinical trials that use novel techniques including emerging information and communication technologies to explore important research questions rapidly and at a fraction of the cost incurred by more "traditional" research methods promise to help close this gap. Nevertheless, while pragmatic clinical trials can bridge clinical practice and research, they may also raise difficult ethical and regulatory challenges. In this article, the authors briefly survey the current state of evidence that is available to inform clinical care and other health-related decisions and discuss the potential for pragmatic clinical trials to improve this state of affairs. They then propose a new working definition for pragmatic research that centers upon fitness for informing decisions about health and health care. Finally, they introduce a project, jointly undertaken by the National Institutes of Health Health Care Systems Research Collaboratory and the National Patient-Centered Clinical Research Network (PCORnet), which addresses 11 key aspects of current systems for regulatory and ethical oversight of clinical research that pose challenges to conducting pragmatic clinical trials. In the series of articles commissioned on this topic published in this issue of Clinical Trials, each of these aspects is addressed in a dedicated article, with a special focus on the interplay between ethical and regulatory considerations and pragmatic clinical research aimed at informing "real-world" choices about health and health care.

Topics: Biomedical Research; Clinical Trials as Topic; Decision Making; Humans; National Institutes of Health (U.S.); Research Design; Surveys and Questionnaires; United States

PubMed: 26374676
DOI: 10.1177/1740774515598334

Authors: P H Canter, E Ernst

Topics: Clinical Trials as Topic; European Union

PubMed: 14996952
DOI: 10.1177/014107680409700301