-
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 -
Current Opinion in Pulmonary Medicine Jan 2018Comparative efficacy trials are designed to evaluate the harms and benefits of health care in a research environment. There is increasing interest in the results of... (Review)
Review
PURPOSE OF REVIEW
Comparative efficacy trials are designed to evaluate the harms and benefits of health care in a research environment. There is increasing interest in the results of comparative effectiveness trials, which are intended to fill gaps in evidence to inform decision-making in real-life clinical environments. The objective of this report is to review various tools to classify trials along the efficacy to effectiveness continuum.
RECENT FINDINGS
Three tools [Pragmatic-Explanatory Continuum Indicator Summary (PRECIS), PRECIS-2, and PRAgmatic Clinical Trial Assessment Scale (PRACTAS)] are available that use a star diagram to illustrate where each element of a clinical trial design falls along the efficacy to effectiveness continuum (e.g., selectivity of eligibility criteria, supports to promote participant adherence). The number and type of design element to be classified varies (e.g., 10 elements for PRECIS and PRACTAS vs. nine elements for PRECIS-2; only the PRACTAS tool includes stakeholder engagement). There is substantial interrater reliability when using all three tools and interrater reliability varies across the different design elements (intraclass correlation of coefficient 0.4-0.8).
SUMMARY
The PRECIS, PRECIS-2, and PRACTAS tools are options when classifying trials along the efficacy to effectiveness continuum. Researchers and decision-making stakeholders are likely to disagree about the extent to which clinical trials employ efficacy or effectiveness designs.
Topics: Asthma; Clinical Trials as Topic; Comparative Effectiveness Research; Decision Support Techniques; Evidence-Based Medicine; Humans; Observer Variation; Reproducibility of Results; Research Design
PubMed: 29076829
DOI: 10.1097/MCP.0000000000000442 -
Trials Oct 2017When a randomised trial is subject to deviations from randomised treatment, analysis according to intention-to-treat does not estimate two important quantities: relative... (Review)
Review
BACKGROUND
When a randomised trial is subject to deviations from randomised treatment, analysis according to intention-to-treat does not estimate two important quantities: relative treatment efficacy and effectiveness in a setting different from that in the trial. Even in trials of a predominantly pragmatic nature, there may be numerous reasons to consider the extent, and impact on analysis, of such deviations from protocol. Simple methods such as per-protocol or as-treated analyses, which exclude or censor patients on the basis of their adherence, usually introduce selection and confounding biases. However, there exist appropriate causal estimation methods which seek to overcome these inherent biases, but these methods remain relatively unfamiliar and are rarely implemented in trials.
METHODS
This paper demonstrates when it may be of interest to look beyond intention-to-treat analysis for answers to alternative causal research questions through illustrative case studies. We seek to guide trialists on how to handle treatment changes in the design, conduct and planning the analysis of a trial; these changes may be planned or unplanned, and may or may not be permitted in the protocol. We highlight issues that must be considered at the trial planning stage relating to: the definition of nonadherence and the causal research question of interest, trial design, data collection, monitoring, statistical analysis and sample size.
RESULTS AND CONCLUSIONS
During trial planning, trialists should define their causal research questions of interest, anticipate the likely extent of treatment changes and use these to inform trial design, including the extent of data collection and data monitoring. A series of concise recommendations is presented to guide trialists when considering undertaking causal analyses.
Topics: Bias; Data Interpretation, Statistical; Drug Substitution; Endpoint Determination; Guideline Adherence; Humans; Infant; Intention to Treat Analysis; Patient Compliance; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Research Design; Sample Size; Treatment Outcome
PubMed: 29070048
DOI: 10.1186/s13063-017-2240-9 -
Journal of the National Cancer... Dec 2022Although adults aged 65 years or older make up a strong majority of cancer patients, their underrepresentation in cancer clinical trials leads to the lack of...
Although adults aged 65 years or older make up a strong majority of cancer patients, their underrepresentation in cancer clinical trials leads to the lack of representative data to guide evidence-based therapeutic decisions in this patient population. The Trial Design Working Group, convened as part of the workshop titled, Engaging Older Adults in the National Cancer Institute Clinical Trials Network: Challenges and Opportunities, recommended study designs and design elements that could improve accrual of older adults in National Cancer Institute-funded clinical trials. These include trials that are specifically designed to enroll older adults, trials that include a cohort of older patients (parallel cohort, stratified cohort, or embedded cohort), and trials with pragmatic design elements to facilitate enrollment of older adults. This manuscript provides brief descriptions of the recommended designs, examples of successful trials, and considerations for implementation of these designs. As with any clinical trial, the scientific questions and trial objectives should drive the study design, the selection of endpoints and intervention, and eligibility criteria. When designing trials that include older adults, the heterogeneity of fitness levels is an important consideration as fitness can influence accrual rates and outcomes. Appropriately incorporating geriatric assessments can help identify the optimal subset of older patients for inclusion and minimize selection bias. Incorporating pragmatic design elements to reduce the burden on trial participants as well as on accruing sites and retaining essential elements to ensure that the main goal of the trial can be accomplished can enhance enrollment without compromising the integrity of trials.
Topics: Aged; Humans; Eligibility Determination; National Cancer Institute (U.S.); Neoplasms; Research Design; United States; Clinical Trials as Topic; Patient Selection
PubMed: 36519818
DOI: 10.1093/jncimonographs/lgac023 -
Ugeskrift For Laeger Jul 2015High-quality scientific evidence may be inadequate to support real world decision-making. Assessment of applicability and generalizability of medical scientific evidence... (Review)
Review
High-quality scientific evidence may be inadequate to support real world decision-making. Assessment of applicability and generalizability of medical scientific evidence is needed for the practitioner. Often, large differences between trial participants and actual end-users of interventions exist. We present the difference between efficacy and effectiveness in connection with trial design and encourage critical evaluation of external validity. Pragmatic design of trials can be considered a preferred choice to limit the prevailing gap between current evidence and practice.
Topics: Biomedical Research; Humans; Pragmatic Clinical Trials as Topic; Research Design
PubMed: 26238009
DOI: No ID Found -
BMC Medicine May 2016Randomized controlled trials (RCTs) are the 'gold standard' in the generation of drug efficacy and safety evidence. However, enrolment criteria, timelines and atypical...
BACKGROUND
Randomized controlled trials (RCTs) are the 'gold standard' in the generation of drug efficacy and safety evidence. However, enrolment criteria, timelines and atypical comparators of RCTs limit their relevance to standard clinical practice.
DISCUSSION
Real-world data (RWD) provide longitudinal information on the comparative effectiveness and tolerability of drugs, as well as their impact on resource use, medical costs, and pharmacoeconomic and patient-reported outcomes. This is particularly important in multiple sclerosis (MS), where economic treatment benefits of long-term disability reduction are a cornerstone of payer drug approvals - these are typically not examined in the RCT itself but modelled using real-world datasets. Importantly, surrogate markers used in RCTs to predict the prevention of long-term disability progression can only truly be assessed through RWD methodologies. We discuss the differences between RCTs and RWD studies, describe how RWD complements the evidence base from RCTs in MS, summarize the different methods of RWD collection, and explain the importance of structuring data analysis to avoid bias. Guidance on performing and identifying high-quality real-world evidence studies is also provided.
Topics: Disease Progression; Evidence-Based Practice; Humans; Longitudinal Studies; Multiple Sclerosis; Pragmatic Clinical Trials as Topic
PubMed: 27246898
DOI: 10.1186/s12916-016-0627-1 -
Clinical Trials (London, England) Aug 2019While conducting a set of large-scale multi-site pragmatic clinical trials involving high-impact public health issues such as end-stage renal disease, opioid use, and...
While conducting a set of large-scale multi-site pragmatic clinical trials involving high-impact public health issues such as end-stage renal disease, opioid use, and colorectal cancer, there were substantial changes to both policies and guidelines relevant to the trials. These external changes gave rise to unexpected challenges for the trials, including decisions regarding how to respond to new clinical practice guidelines, increased difficulty in implementing trial interventions, achieving separation between treatment groups, and differential responses across sites. In this article, we describe these challenges and the approaches used to address them. When deliberating appropriate action in the face of external changes during a pragmatic clinical trial, we recommend considering the well-being of the participants, clinical equipoise, and the strength and quality of the evidence associated with the change; involving those charged with data and safety monitoring; and where possible, planning for potential external changes as the trial is being designed. Any solution must balance the primary obligation to protect the well-being of participants with the secondary obligation to protect the integrity of the trial in order to gain meaningful answers to important public health questions.
Topics: Colorectal Neoplasms; Humans; Insurance, Health, Reimbursement; Kidney Failure, Chronic; Opioid-Related Disorders; Practice Guidelines as Topic; Pragmatic Clinical Trials as Topic; Public Health; Research Design
PubMed: 31084378
DOI: 10.1177/1740774519845682 -
Fertility and Sterility Jun 2018Randomized clinical trials are considered the preferred approach for comparing the effects of treatments, yet data from high-quality clinical trials are often... (Review)
Review
Randomized clinical trials are considered the preferred approach for comparing the effects of treatments, yet data from high-quality clinical trials are often unavailable and many clinical decisions are made on the basis of evidence from observational studies. Using clinical examples about the management of infertility, we discuss how we can use observational data from large and information-rich health-care databases combined with modern epidemiological and statistical methods to learn about the effects of interventions when clinical trial evidence is unavailable or not applicable to the clinically relevant target population. When trial evidence is unavailable, we can conduct observational analyses emulating the hypothetical pragmatic target trials that would address the clinical questions of interest. When trial evidence is available but not applicable to the clinically relevant target population, we can transport inferences from trial participants to the target population using the trial data and a sample of observational data from the target population. Clinical trial emulations and transportability analyses can be coupled with methods for examining heterogeneity of treatment effects, providing a path toward personalized medicine.
Topics: Access to Information; Clinical Trials as Topic; Databases, Factual; Decision Making; Evidence-Based Medicine; Humans; Observational Studies as Topic; Precision Medicine; Research Design
PubMed: 29935652
DOI: 10.1016/j.fertnstert.2018.04.005 -
Psychiatry Research Jan 2017Schizophrenia presents unique difficulties in clinical trial design associated with the condition's variable presentation and clinical course, and multiple features... (Review)
Review
Schizophrenia presents unique difficulties in clinical trial design associated with the condition's variable presentation and clinical course, and multiple features influencing affect, cognition, volition and perception. Randomized controlled trials (RCTs) are explanatory studies using a carefully selected patient population, predefined assessment intervals and, generally, symptom-focused endpoints. Naturalistic studies are pragmatic, with no active intervention, and outcomes that are generally those used in clinical practice (e.g. hospitalization, relapse rate). Both naturalistic studies and RCTs have pros and cons, making it difficult for physicians in clinical practice to apply research findings to their own treatment decisions. The choice of clinical trial design can have a significant impact on the comparative effectiveness or efficacy of drugs. This is particularly true for studies comparing long-acting injectable (LAI) antipsychotics with oral antipsychotics in schizophrenia, in which RCTs generally show no benefit for LAIs over oral drugs, whereas observational studies do. The more pragmatic the study design, the more likely it is to show a benefit for LAIs versus oral therapy. This article reviews the pros and cons of different study types, using published examples. Criteria are outlined to help physicians design appropriate prospective studies in schizophrenia including the relevant pragmatic and/or explanatory features, as required.
Topics: Antipsychotic Agents; Humans; Pragmatic Clinical Trials as Topic; Randomized Controlled Trials as Topic; Research Design; Schizophrenia
PubMed: 27936437
DOI: 10.1016/j.psychres.2016.11.044