-
Journal of Clinical Epidemiology Jan 2020Factorial designs can allow efficient evaluation of multiple treatments within a single trial. We evaluated the design, analysis, and reporting in a sample of factorial... (Review)
Review
OBJECTIVES
Factorial designs can allow efficient evaluation of multiple treatments within a single trial. We evaluated the design, analysis, and reporting in a sample of factorial trials.
STUDY DESIGN AND SETTING
Review of 2 × 2 factorial trials evaluating health-related interventions and outcomes in humans. Using Medline, we identified articles published between January 2015 and March 2018. We randomly selected 100 articles for inclusion.
RESULTS
Most trials (78%) did not provide a rationale for using a factorial design. Only 63 trials (63%) assessed the interaction for the primary outcome, and 39/63 (62%) made a further assessment for at least one secondary outcome. 12/63 trials (19%) identified a significant interaction for the primary outcome and 16/39 trials (41%) for at least one secondary outcome. Inappropriate methods of analysis to protect against potential negative effects from interactions were common, with 18 trials (18%) choosing the analysis method based on a preliminary test for interaction, and 13% (n = 10/75) of those conducting a factorial analysis including an interaction term in the model.
CONCLUSION
Reporting of factorial trials was often suboptimal, and assessment of interactions was poor. Investigators often used inappropriate methods of analysis to try to protect against adverse effects of interactions.
Topics: Clinical Trials as Topic; Data Interpretation, Statistical; Humans; Research Design
PubMed: 31585174
DOI: 10.1016/j.jclinepi.2019.09.018 -
Clinical Trials (London, England) Aug 2020Electronic health record data can be used in multiple ways to facilitate real-world pragmatic studies. Electronic health record data can provide detailed information...
Electronic health record data can be used in multiple ways to facilitate real-world pragmatic studies. Electronic health record data can provide detailed information about utilization of treatment options to help identify appropriate comparison groups, access historical clinical characteristics of participants, and facilitate measuring longitudinal outcomes for the treatments being studied. An additional novel use of electronic health record data is to assess and understand referral pathways and other business practices that encourage or discourage patients from using different types of care. We describe an ongoing study utilizing access to real-time electronic health record data about changing patterns of complementary and integrative health services to demonstrate how electronic health record data can provide the foundation for a pragmatic study when randomization is not feasible. Conducting explanatory trials of the value of emerging therapies within a healthcare system poses ethical and pragmatic challenges, such as withholding access to specific services that are becoming widely available to patients. We describe how prospective examination of real-time electronic health record data can be used to construct and understand business practices as potential surrogates for direct randomization through an instrumental variables analytic approach. In this context, an example of a business practice is the internal hiring of acupuncturists who also provide yoga or Tai Chi classes and can offer these classes without additional cost compared to community acupuncturists. Here, the business practice of hiring internal acupuncturists is likely to encourage much higher rates of combined complementary and integrative health use compared to community referrals. We highlight the tradeoff in efficiency of this pragmatic approach and describe use of simulations to estimate the potential sample sizes needed for a variety of instrument strengths. While real-time monitoring of business practices from electronic health records provides insights into the validity of key independence assumptions associated with the instrumental variable approaches, we note that there may be some residual confounding by indication or selection bias and describe how alternative sources of electronic health record data can be used to assess the robustness of instrumental variable assumptions to address these challenges. Finally, we also highlight that while some clinical outcomes can be obtained directly from the electronic health record, such as longitudinal opioid utilization and pain intensity levels for the study of the value of complementary and integrative health, it is often critical to supplement clinical electronic health record-based measures with patient-reported outcomes. The experience of this example in evaluating complementary and integrative health demonstrates the use of electronic health record data in several novel ways that may be of use for designing future pragmatic trials.
Topics: Complementary Therapies; Computer Simulation; Electronic Health Records; Humans; Integrative Medicine; Pain; Pain Management; Pain Measurement; Patient Reported Outcome Measures; Pragmatic Clinical Trials as Topic; Prospective Studies; Referral and Consultation; Research Design; Sample Size; Self Care
PubMed: 32522024
DOI: 10.1177/1740774520928399 -
Recenti Progressi in Medicina Nov 2019
Topics: Control Groups; Data Interpretation, Statistical; Databases, Factual; Equivalence Trials as Topic; Evidence-Based Medicine; Humans; Observational Studies as Topic; Pharmaceutical Preparations; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Reproducibility of Results; Technology Assessment, Biomedical; Technology Transfer; Time Factors; Treatment Outcome
PubMed: 31808432
DOI: 10.1701/3265.32327 -
Recenti Progressi in Medicina Nov 2019
Topics: Humans; Informed Consent; Observational Studies as Topic; Pragmatic Clinical Trials as Topic; Prospective Studies; Random Allocation; Risk Assessment; Uncertainty
PubMed: 31808438
DOI: 10.1701/3265.32354 -
Contemporary Clinical Trials Oct 2022Efficiency in clinical trial recruitment and enrollment remains a major challenge in many areas of clinical medicine. In particular, despite the prevalence of heart... (Review)
Review
Efficiency in clinical trial recruitment and enrollment remains a major challenge in many areas of clinical medicine. In particular, despite the prevalence of heart failure with preserved ejection fraction (HFpEF), identifying patients with HFpEF for clinical trials has proven to be especially challenging. In this manuscript, we review strategies for contemporary clinical trial recruitment and present insights from the results of the DELIVER Electronic Health Record (EHR) Screening Initiative. The DELIVER trial was designed to evaluate the effects of dapagliflozin on clinical outcomes in patients with HFpEF. Within this trial, the multicenter DELIVER EHR Screening Initiative utilized EHR-based techniques in order to improve recruitment at selected sites in the United States. For this initiative, we developed and deployed a computable phenotype from the trial's eligibility criteria along with additional EHR tools at interested sites. Sites were then surveyed at the end of the program regarding lessons learned. Six sites were recruited, trained, and supported to utilize the EHR methodology and computable phenotype. Sites found the initiative to be helpful in identifying eligible patients and cited the individualized expert technical support as a critical factor in utilizing the program effectively. We found that the major challenge of implementation was the process of converting traditional inclusion/exclusion criteria into a computable phenotype within an established and ongoing trial. Other significant challenges noted by sites were the following: impact of the COVID-19 pandemic, engagement/support by local institutions, and limited availability of internal EHR experts/resources to execute programming. The study represents a proof-of-concept in the ability to utilize EHR-based tools in clinical trial recruitment for patients with HFpEF and provides important lessons for future initiatives. ClinicalTrials.gov Identifier: NCT03619213.
Topics: COVID-19; Clinical Trials as Topic; Electronic Health Records; Heart Failure; Humans; Multicenter Studies as Topic; Pandemics; Stroke Volume
PubMed: 36100197
DOI: 10.1016/j.cct.2022.106924 -
Trials Mar 2021Along with its heavy toll of morbidity and mortality, the coronavirus disease 2019 (COVID-19) pandemic exposed several limitations of the current global research... (Review)
Review
Along with its heavy toll of morbidity and mortality, the coronavirus disease 2019 (COVID-19) pandemic exposed several limitations of the current global research response. The slow and inefficient process of carrying out traditional randomized clinical trials led regulatory authorities to hastily approve treatments and tests without sufficient evidence of safety and efficacy.We here outline issues with the current research platform, summarize shortcomings of traditional randomized clinical trials particularly apparent at the time of pandemics, and highlight the advantages of pragmatic clinical trials as an alternative to rapidly generate the needed clinical evidence. We further discuss barriers and challenges to pragmatic clinical trials implementation and explore opportunities for research institutions and regulatory authorities to facilitate widespread adoption of this vital research tool.As a subsequent wave of COVID-19, and/or another epidemic, are all but inevitable in our lifetime, we must ensure that our research infrastructure is conducive to carrying out pragmatic clinical trials to expeditiously generate the needed evidence and blunt the epidemic's toll on human lives and livelihoods.
Topics: COVID-19; Drug Approval; Evidence-Based Medicine; Humans; Pragmatic Clinical Trials as Topic; Research Design
PubMed: 33761968
DOI: 10.1186/s13063-021-05165-0 -
Trials Jun 2024Randomized controlled trials (RCTs) are rigorous scientific research designs for evaluating intervention effectiveness. However, implementing RCTs in a real-world...
Strengths, challenges, and strategies for implementing pragmatic multicenter randomized controlled trials (RCTs): example of the Personalized Citizen Assistance for Social Participation (APIC) trial.
BACKGROUND
Randomized controlled trials (RCTs) are rigorous scientific research designs for evaluating intervention effectiveness. However, implementing RCTs in a real-world context is challenging. To develop strategies to improve its application, it is essential to understand the strengths and challenges of this design. This study thus aimed to explore the strengths, challenges, and strategies for improving the implementation of a pragmatic multicenter, prospective, two-arm RCT evaluating the effects of the Personalized Citizen Assistance for Social Participation (Accompagnement-citoyen Personnalisé d'Intégration Communautaire: APIC; weekly 3-h personalized stimulation sessions given by a trained volunteer over a 12-month period) on older adults' health, social participation, and life satisfaction.
METHODS
A multiple case study was conducted with 14 participants, comprising one research assistant, seven coordinators, and six managers of six community organizations serving older adults, who implemented the APIC in the context of a RCT. Between 2017 and 2023, qualitative data were extracted from 24 group meetings, seven semi-directed interviews, emails exchanged with the research team, and one follow-up document.
RESULTS
Aged between 30 and 60 (median ± SIQR: 44.0 ± 6.3), most participants were women from organizations already offering social participation interventions for older adults and working with the public sector. Reported strengths of this RCT were its relevance in assessing an innovative intervention to support healthy aging, and the sharing of common goals, expertise, and strategies with community organizations. Challenges included difficulties recruiting older adults, resistance to potential control group assignments, design complexity, and efforts to mobilize and engage volunteers. The COVID-19 pandemic lockdown and health measures exacerbated challenges related to recruiting older adults and mobilizing volunteers and complicated delivery of the intervention. The strategies that mostly overcame difficulties in recruiting older adults were reducing sample size, simplifying recruitment procedures, emphasizing the health follow-up, extending partnerships, and recognizing and supporting volunteers better. Because of the lockdown and physical distancing measures, the intervention was also adapted for remote delivery, including via telephone or videoconferencing.
CONCLUSION
Knowledge of the strengths and challenges of pragmatic RCTs can contribute to the development of strategies to facilitate implementation studies and better evaluate health and social participation interventions delivered under real-life conditions.
TRIAL REGISTRATION
NCT03161860; Pre-results. Registered on May 22, 2017.
Topics: Humans; Social Participation; Female; Male; Middle Aged; Prospective Studies; Adult; Volunteers; Research Design; COVID-19; Randomized Controlled Trials as Topic; Pragmatic Clinical Trials as Topic; Aged; Personal Satisfaction; Multicenter Studies as Topic
PubMed: 38937798
DOI: 10.1186/s13063-024-08248-w -
Healthcare (Amsterdam, Netherlands) Dec 2021While the embedded nature of pragmatic clinical trials (PCTs) can improve the efficiency and relevance of research for multiple stakeholders, embedding research into...
While the embedded nature of pragmatic clinical trials (PCTs) can improve the efficiency and relevance of research for multiple stakeholders, embedding research into ongoing clinical care can also involve ethical and regulatory challenges. An emergent challenge is the management of pragmatic clinical trial collateral findings (PCT-CFs). While PCT-CFs share some features with incidental or secondary findings that are encountered in conventional clinical trials and clinical care, the PCT context differs in ethically relevant ways that complicate PCT-CF identification and management. We report on the results of a two-year multi-method investigation of PCT-CFs. Overall, five core themes emerged: 1) the liminal nature of PCTs and the implications of this for PCT-CFs; 2) the context-specific nature of PCT-CF management; 3) the centrality of institutions; 4) the importance of prospective planning; and 5) patient expectations. Among the central lessons of this work are that prior ethics guidance from other settings cannot easily be adapted to address PCT-CFs, nor can a single approach readily accommodate all PCT-CFs. Moving forward, stakeholders, including researchers, institutions, ethics oversight bodies, and funders, should anticipate and plan for PCT-CFs in the design, conduct, and analysis of PCTs. Future scholarship is needed to examine experiences with PCT-CFs, and the practical and conceptual issues they raise for the future conduct of PCTs.
Topics: Humans; Pragmatic Clinical Trials as Topic; Prospective Studies; Research Design; Research Personnel
PubMed: 34600345
DOI: 10.1016/j.hjdsi.2021.100586 -
European Journal of Clinical Nutrition Dec 2023Evidence-based nutritional recommendations address the health impact of suboptimal nutritional status. Efficacy randomized controlled trials (RCTs) have traditionally... (Review)
Review
Evidence-based nutritional recommendations address the health impact of suboptimal nutritional status. Efficacy randomized controlled trials (RCTs) have traditionally been the preferred method for determining the effects of nutritional interventions on health outcomes. Nevertheless, obtaining a holistic understanding of intervention efficacy and effectiveness in real-world settings is stymied by inherent constraints of efficacy RCTs. These limitations are further compounded by the complexity of nutritional interventions and the intricacies of the clinical context. Herein, we explore the advantages and limitations of alternative study designs (e.g., adaptive and pragmatic trials), which can be incorporated into RCTs to optimize the efficacy or effectiveness of interventions in clinical nutrition research. Efficacy RCTs often lack external validity due to their fixed design and restrictive eligibility criteria, leading to efficacy-effectiveness and evidence-practice gaps. Adaptive trials improve the evaluation of nutritional intervention efficacy through planned study modifications, such as recalculating sample sizes or discontinuing a study arm. Pragmatic trials are embedded within clinical practice or conducted in settings that resemble standard of care, enabling a more comprehensive assessment of intervention effectiveness. Pragmatic trials often rely on patient-oriented primary outcomes, acquire outcome data from electronic health records, and employ broader eligibility criteria. Consequently, adaptive and pragmatic trials facilitate the prompt implementation of evidence-based nutritional recommendations into clinical practice. Recognizing the limitations of efficacy RCTs and the potential advantages of alternative trial designs is essential for bridging efficacy-effectiveness and evidence-practice gaps. Ultimately, this awareness will lead to a greater number of patients benefiting from evidence-based nutritional recommendations.
Topics: Humans; Nutritional Status; Research Design; Pragmatic Clinical Trials as Topic; Adaptive Clinical Trials as Topic
PubMed: 37715007
DOI: 10.1038/s41430-023-01330-7 -
Rheumatology (Oxford, England) Jan 2020Health-related information is increasingly being collected and stored digitally. These data, either structured or unstructured, are becoming the ubiquitous assets that... (Review)
Review
Health-related information is increasingly being collected and stored digitally. These data, either structured or unstructured, are becoming the ubiquitous assets that might enable us to comprehensively map out a patient's health journey from an asymptomatic state of wellness to disease onset and its trajectory. These new data could provide rich real-world evidence for better clinical care and research, if they can be accessed, linked and analyzed-all of which are possible. In this review, these opportunities will be explored through a case vignette of a patient with OA, followed by discussion on how this digitalized real-world evidence could best be utilized, as well as the challenges of data access, quality and maintaining public trust.
Topics: Humans; Medical Records Systems, Computerized; Mobile Applications; Pragmatic Clinical Trials as Topic; Research Design
PubMed: 31834405
DOI: 10.1093/rheumatology/kez068