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Surgical Infections Aug 2021The goal of a randomized or observational study is to develop an unbiased and reliable answer to a therapeutic question. However, there are multiple pitfalls in the... (Review)
Review
The goal of a randomized or observational study is to develop an unbiased and reliable answer to a therapeutic question. However, there are multiple pitfalls in the reporting and interpretation of data that can compromise our ability to evaluate the pragmatism and the effectiveness of the intervention being studied. Researchers must be conscious of these biases when designing their studies, just as readers must be aware of these potential pitfalls when interpreting results. The purpose of this review is to highlight some of the more common sources of bias in clinical research, including internal and external validity, type 1 and type 2 error, reporting of secondary outcomes, the use of subgroup analyses, and multiple comparisons. This article also discusses potential solutions to these issues, including using the fragility index to understand the robustness of study conclusions, and generating an E value to determine the degree of unmeasured confounding in a study. With an understanding of these pitfalls, readers can critically review scientific literature and ascertain the validity of the conclusions.
Topics: Bias; Biomedical Research; Clinical Trials as Topic; Data Interpretation, Statistical; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; Surgical Wound Infection
PubMed: 34270363
DOI: 10.1089/sur.2021.074 -
Seminars in Radiation Oncology Oct 2023The concept of informed consent has evolved considerably over the course of the 20th century, leading to its establishment as a foundational ethical principle for the... (Review)
Review
The concept of informed consent has evolved considerably over the course of the 20th century, leading to its establishment as a foundational ethical principle for the conduct of biomedical research in the United States. Even though it is now a highly regulated part of cancer research, the process of obtaining informed consent is often impeded by systemic, clinician, and patient factors that require both small- and large-scale intervention. New challenges and considerations continue to emerge due to innovations in clinical trial design, increases in utilization of genomic sequencing, and advances in genomic editing and artificial intelligence. We present a review of the history, policy, pragmatic challenges, and evolving role of the central ethical tenet of informed consent in clinical trials.
Topics: Humans; Artificial Intelligence; Clinical Trials as Topic; Informed Consent; Neoplasms
PubMed: 37684064
DOI: 10.1016/j.semradonc.2023.06.001 -
Hepatology (Baltimore, Md.) Mar 2024Patients with chronic liver disease would benefit from pragmatic trial designs. A pragmatic trial seeks to inform clinical decision-making by providing evidence for the... (Review)
Review
Patients with chronic liver disease would benefit from pragmatic trial designs. A pragmatic trial seeks to inform clinical decision-making by providing evidence for the adoption of an intervention into real-world clinical practice. A trial's pragmatism is based on the efficiency by which it identifies, recruits, and follows patients, the degree to which the interventions and design mirror the usual clinical care, and the importance of the outcomes to the patients. We review the promise, trade-offs, and purpose of pragmatic trials in hepatology.
Topics: Humans; Gastroenterology; Pragmatic Clinical Trials as Topic
PubMed: 36825597
DOI: 10.1097/HEP.0000000000000345 -
Academic Emergency Medicine : Official... Oct 2022Pragmatic clinical trials (PCTs) focus on correlation between treatment and outcomes in real-world clinical practice, yet a guide highlighting key study considerations...
Pragmatic clinical trials (PCTs) focus on correlation between treatment and outcomes in real-world clinical practice, yet a guide highlighting key study considerations and design types for emergency medicine investigators pursuing this important study type is not available. Investigators conducting emergency department (ED)-based PCTs face multiple decisions within the planning phase to ensure robust and meaningful study findings. The PRagmatic Explanatory Continuum Indicator Summary 2 (PRECIS-2) tool allows trialists to consider both pragmatic and explanatory components across nine domains, shaping the trial design to the purpose intended by the investigators. Aside from the PRECIS-2 tool domains, ED-based investigators conducting PCTs should also consider randomization techniques, human subjects concerns, and integration of trial components within the electronic health record. The authors additionally highlight the advantages, disadvantages, and rationale for the use of four common randomized study design types to be considered in PCTs: parallel, crossover, factorial, and stepped-wedge. With increasing emphasis on the conduct of PCTs, emergency medicine investigators will benefit from a rigorous approach to clinical trial design.
Topics: Emergency Medicine; Humans; Pragmatic Clinical Trials as Topic; Research Design
PubMed: 35475533
DOI: 10.1111/acem.14513 -
Mayo Clinic Proceedings Oct 2023Now, more than ever, digital technology has made its way into the daily lives of billions across the globe, and the widespread use of this technology has also allowed a... (Review)
Review
Now, more than ever, digital technology has made its way into the daily lives of billions across the globe, and the widespread use of this technology has also allowed a digital window into consumers' and patients' daily lives, respectively. In a similar way, the practice of medicine has digitally evolved with the application of electronic health records and development of wearable/portable consumer-based medical devices (eg, Apple Watch ECG and Kardia Mobile by AliveCor). Alongside the increased use of digital technology in clinical care (eg, telehealth and wearable arrhythmia detection), clinical investigators have harnessed this powerful stockpile of data to gain insight into what happens to patients beyond the clinic walls. In this thematic review, we show the impact of digital advancements on the clinical trial process from recruitment and enrollment to interventions and data collection. We also show the pragmatism of this decentralized process and how it will mitigate the limitations of conventional randomized controlled trials. Finally, while pushing the boundaries of tech, we also describe a few limitations of this rapidly growing field to understand better what gaps need to be bridged in the future.
Topics: Humans; Forecasting; Telemedicine; Wearable Electronic Devices; Clinical Trials as Topic
PubMed: 36669937
DOI: 10.1016/j.mayocp.2022.10.001 -
Psychological Medicine Jan 2015At more than 10 years after the paper by Hotopf and colleagues regarding pragmatic trials in psychiatry, the field has evolved and is evolving further. There have been...
At more than 10 years after the paper by Hotopf and colleagues regarding pragmatic trials in psychiatry, the field has evolved and is evolving further. There have been many developments in our understanding of what pragmatism really means, and excellent examples of truly pragmatic trials in psychiatry are currently available. Funders have helped encourage more emphasis on the need for such studies, but 'local' and trans-national regulations could help more. Consumers of the evidence should have a greater voice in generating the research agenda and, as this happens, the questions generated are more likely to be answered by a pragmatic approach to trials.
Topics: Humans; Pragmatic Clinical Trials as Topic; Psychiatry; Research Design
PubMed: 25065958
DOI: 10.1017/S0033291714001275 -
BMJ Open Dec 2022To describe the extent to which pragmatic trials underachieved or overachieved their target sample sizes, examine explanations and identify characteristics associated...
Reporting of and explanations for under-recruitment and over-recruitment in pragmatic trials: a secondary analysis of a database of primary trial reports published from 2014 to 2019.
OBJECTIVES
To describe the extent to which pragmatic trials underachieved or overachieved their target sample sizes, examine explanations and identify characteristics associated with under-recruitment and over-recruitment.
STUDY DESIGN AND SETTING
Secondary analysis of an existing database of primary trial reports published during 2014-2019, registered in ClinicalTrials.gov, self-labelled as pragmatic and with target and achieved sample sizes available.
RESULTS
Of 372 eligible trials, the prevalence of under-recruitment (achieving <90% of target sample size) was 71 (19.1%) and of over-recruitment (>110% of target) was 87 (23.4%). Under-recruiting trials commonly acknowledged that they did not achieve their targets (51, 71.8%), with the majority providing an explanation, but only 11 (12.6%) over-recruiting trials acknowledged recruitment excess. The prevalence of under-recruitment in individually randomised versus cluster randomised trials was 41 (17.0%) and 30 (22.9%), respectively; prevalence of over-recruitment was 39 (16.2%) vs 48 (36.7%), respectively. Overall, 101 025 participants were recruited to trials that did not achieve at least 90% of their target sample size. When considering trials with over-recruitment, the total number of participants recruited in excess of the target was a median (Q1-Q3) 319 (75-1478) per trial for an overall total of 555 309 more participants than targeted. In multinomial logistic regression, cluster randomisation and lower journal impact factor were significantly associated with both under-recruitment and over-recruitment, while using exclusively routinely collected data and educational/behavioural interventions were significantly associated with over-recruitment; we were unable to detect significant associations with obtaining consent, publication year, country of recruitment or public engagement.
CONCLUSIONS
A clear explanation for under-recruitment or over-recruitment in pragmatic trials should be provided to encourage transparency in research, and to inform recruitment to future trials with comparable designs. The issues and ethical implications of over-recruitment should be more widely recognised by trialists, particularly when designing cluster randomised trials.
Topics: Humans; Databases, Factual; Prevalence; Publications; Sample Size; Pragmatic Clinical Trials as Topic; Patient Selection
PubMed: 36600344
DOI: 10.1136/bmjopen-2022-067656 -
Osteoarthritis and Cartilage Mar 2021
Topics: Cognitive Behavioral Therapy; Humans; Low Back Pain; Mediation Analysis; Patient Satisfaction; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33429055
DOI: 10.1016/j.joca.2020.12.011 -
Circulation Oct 2019The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of... (Review)
Review
The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of new drugs and devices. Nevertheless, the growing use of electronic health records, mobile applications, and wearable devices offers significant promise for transforming clinical trials, making them more pragmatic and efficient. However, many challenges must be overcome before these innovations can be implemented routinely in randomized, controlled trial operations. In October of 2018, a diverse stakeholder group convened in Washington, DC, to examine how electronic health record, mobile, and wearable technologies could be applied to clinical trials. The group specifically examined how these technologies might streamline the execution of clinical trial components, delineated innovative trial designs facilitated by technological developments, identified barriers to implementation, and determined the optimal frameworks needed for regulatory oversight. The group concluded that the application of novel technologies to clinical trials provided enormous potential, yet these changes needed to be iterative and facilitated by continuous learning and pilot studies.
Topics: Clinical Trials as Topic; Electronic Health Records; Humans; Mobile Applications; Research Design; Wearable Electronic Devices
PubMed: 31634011
DOI: 10.1161/CIRCULATIONAHA.119.040798 -
Clinical Trials (London, England) Dec 2021Pragmatic clinical trials are increasingly used to generate knowledge about real-world clinical interventions. However, they involve some distinctive ethical and...
Pragmatic clinical trials are increasingly used to generate knowledge about real-world clinical interventions. However, they involve some distinctive ethical and regulatory challenges. In this article, we examine a set of issues related to incentives and other payments to patients in pragmatic clinical trials. Although many of the ethical concerns related to incentives and payments in explanatory trials pertain to pragmatic clinical trials, the pragmatic features may introduce additional challenges. These include those related to the risk of incentives and payments undermining the scientific validity and social value of pragmatic clinical trials, the sources of data used in pragmatic clinical trials, and when the pragmatic clinical trials are conducted under waivers of consent. Based on our examination of these matters, we offer some preliminary recommendations regarding incentives and payments in pragmatic clinical trials, recognizing that additional data and experiences are needed to refine them.
Topics: Ethics, Research; Humans; Motivation; Policy; Pragmatic Clinical Trials as Topic; Research Design
PubMed: 34766524
DOI: 10.1177/17407745211048178