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CMAJ Open 2023There are few data on patient and public involvement (PPI) in pragmatic trials. We aimed to describe the prevalence and nature of PPI within pragmatic trials, describe...
BACKGROUND
There are few data on patient and public involvement (PPI) in pragmatic trials. We aimed to describe the prevalence and nature of PPI within pragmatic trials, describe variation in prevalence of PPI by trial characteristics and compare prevalence of PPI reported by trial authors to that reported in trial publications.
METHODS
We applied a search filter to identify pragmatic trials published from 2014 to 2019 in MEDLINE. We invited the corresponding authors of pragmatic trials to participate in an online survey about their specific trial.
RESULTS
Of 3163 authors invited, 2585 invitations were delivered, 710 (27.5%) reported on 710 unique trials and completed the survey; 334 (47.0%) conducted PPI. Among those who conducted PPI, for many the aim was to increase the research relevance (86.3%) or quality (76.5%). Most PPI partners were engaged at protocol development stages (79.1%) and contributed to the co-design of interventions (70.9%) or recruitment or retention strategies (60.5%). Patient and public involvement was more common among trials involving children, trials conducted in the United Kingdom, cluster randomized trials, those explicitly labelled as "pragmatic" in the study manuscript, and more recent trials. Less than one-quarter of trials (22.8%) that reported PPI in the survey also reported PPI in the trial manuscript.
INTERPRETATION
Nearly half of trialists in this survey reported conducting PPI and listed several benefits of doing so, but researchers who did not conduct PPI often cited a lack of requirement for it. Patient and public involvement appears to be significantly underreported in trial publications. Consistent and standardized reporting is needed to promote transparency about PPI methods, outcomes, challenges and benefits.
PubMed: 37726115
DOI: 10.9778/cmajo.20220198 -
Pragmatic and Observational Research 2023There is a growing interest in real world evidence when developing antineoplastic drugs owing to the shorter length of time and low costs compared to randomised... (Review)
Review
There is a growing interest in real world evidence when developing antineoplastic drugs owing to the shorter length of time and low costs compared to randomised controlled trials. External validity of studies in the regulatory phase can be enhanced by complementing randomised controlled trials with real world evidence. Furthermore, the use of real world evidence ensures the inclusion of patients often excluded from randomised controlled trials such as the elderly, certain ethnicities or those from certain geographical areas. This review explores approaches in which real world data may be integrated with randomised controlled trials. One approach is by using big data, especially when investigating drugs in the antineoplastic setting. This can even inform artificial intelligence thus ensuring faster and more precise diagnosis and treatment decisions. Pragmatic trials also offer an approach to examine the effectiveness of novel antineoplastic drugs without evading the benefits of randomised controlled trials. A well-designed pragmatic trial would yield results with high external validity by employing a simple study design with a large sample size and diverse settings. Although randomised controlled trials can determine efficacy of antineoplastic drugs, effectiveness in the real world may differ. The need for pragmatic trials to help guide healthcare decision-making led to the development of trials within cohorts (TWICs). TWICs make use of cohorts to conduct multiple randomised controlled trials while maintaining characteristics of real world data in routine clinical practice. Although real world data is often affected by incomplete data and biases such as selection and unmeasured biases, the use of big data and pragmatic approaches can improve the use of real world data in the development of antineoplastic drugs that can in turn steer decision-making in clinical practice.
PubMed: 37701044
DOI: 10.2147/POR.S395959 -
BMC Anesthesiology Oct 2023ICU survivors often suffer from prolonged physical and mental impairments resulting in the so called "Post-Intensive Care Syndrome" (PICS). The aftercare of former ICU... (Randomized Controlled Trial)
Randomized Controlled Trial
Piloting an ICU follow-up clinic to improve health-related quality of life in ICU survivors after a prolonged intensive care stay (PINA): feasibility of a pragmatic randomised controlled trial.
BACKGROUND
ICU survivors often suffer from prolonged physical and mental impairments resulting in the so called "Post-Intensive Care Syndrome" (PICS). The aftercare of former ICU patients affected by PICS in particular has not been addressed sufficiently in Germany so far. The aim of this study was to evaluate the feasibility of a pragmatic randomised trial (RCT) comparing an intensive care unit (ICU) follow-up clinic intervention to usual care.
METHODS
This pilot study in a German university hospital evaluated the feasibility of a pragmatic RCT. Patients were assigned in a 1:1 ratio to an ICU follow-up clinic intervention or to usual care. The concept of this follow-up clinic was previously developed in a participatory process with patients, next of kin, health care professionals and researchers. We performed a process evaluation and determined acceptability, fidelity, completeness of measurement instruments and practicality as feasibility outcomes. The RCT's primary outcome (health-related quality of life) was assessed six months after ICU discharge by means of the physical component scale of the Short-Form-12 self-report questionnaire.
RESULTS
The pilot study was conducted from June 2020 to May 2021 with 21 and 20 participants in the intervention and control group. Principal findings related to feasibility were 85% consent rate (N = 48), 62% fidelity rate, 34% attrition rate (N = 41) and 77% completeness of outcome measurements. The primary effectiveness outcome (health-related quality of life) could be measured in 93% of participants who completed the study (N = 27). The majority of participants (85%) needed assistance with follow-up questionnaires (practicality). Median length of ICU stay was 13 days and 85% (N = 41) received mechanical ventilation, median Sequential Organ Failure Assessment Score was nine. Six-month follow-up assessment was planned for all study participants and performed for 66% (N = 41) of the participants after 197 days (median).
CONCLUSION
The participatory developed intervention of an ICU follow-up clinic and the pragmatic pilot RCT both seem to be feasible. We recommend to start a pragmatic RCT on the effectiveness of the ICU follow-up clinic.
TRIAL REGISTRATION
ClinicalTrials.gov US NLM, NCT04186468, Submission: 02/12/2019, Registration: 04/12/2019, https://clinicaltrials.gov/ct2/show/NCT04186468.
Topics: Humans; Quality of Life; Follow-Up Studies; Feasibility Studies; Pilot Projects; Intensive Care Units; Critical Care; Survivors
PubMed: 37838669
DOI: 10.1186/s12871-023-02255-1 -
BMC Psychiatry Nov 2023Depression is a common psychiatric disorder and a leading cause of disability worldwide. Conventional monoaminergic antidepressants have limited efficacy and take weeks...
BACKGROUND
Depression is a common psychiatric disorder and a leading cause of disability worldwide. Conventional monoaminergic antidepressants have limited efficacy and take weeks to exert a therapeutic effect. Single infusions of subanaesthetic doses of ketamine exhibit rapid antidepressant action but effects are transient and relapse is common. One potential strategy for increasing ketamine's antidepressant efficacy and/or prolonging its therapeutic benefit may be serial infusions. There is limited evidence on the efficacy and safety of repeated ketamine infusions against an active comparator.
METHODS
This protocol describes an ongoing pragmatic, randomised, controlled, parallel-group, patient- and rater-blind, superiority trial. Eligible adult inpatients with a confirmed DSM-5 diagnosis of a major depressive episode (unipolar or bipolar) are randomly allocated in a 1:1 ratio to a course of up to eight infusions of ketamine or midazolam twice-weekly over four weeks. The primary objective is to assess the efficacy of serial adjunctive ketamine infusions versus active comparator midazolam by measuring Montgomery-Åsberg Depression Rating Scale score difference between arms from before the first infusion to 24 h after the final infusion, supplemented by a 95% confidence interval. To facilitate generalisability of results, the trial takes place under "real world" conditions with both groups continuing to receive regular inpatient care including treatment-as-usual pharmacotherapy, nursing care, and psychological and other therapies during the randomised treatment phase and regular outpatient care thereafter. Participants are monitored for relapse during a 24-week follow-up after the end of the randomised phase. Secondary objectives of the trial are to assess: response and remission rates at the end of randomised phase; relapse status during the 24-week follow-up after the end of the randomised phase; the safety and tolerability of repeated ketamine infusions regarding psychotomimetic and other psychiatric side effects, cognitive side effects, as well as withdrawal symptoms, haemodynamic stability, neurological, urological, and other physical side effects; and quality of life and cost-effectiveness.
DISCUSSION
There is an unmet clinical need for rapidly-acting novel antidepressants. This trial will provide efficacy, safety and health economic data on serial ketamine infusions and thus help inform clinical practice on the potential role of this treatment in the management of depression.
TRIAL REGISTRATION
EudraCT 2019-003109-92. Registered 2 October 2019.
CLINICALTRIALS
gov NCT04939649. Registered 25 June 2021.
Topics: Adult; Humans; Depressive Disorder, Major; Ketamine; Depression; Midazolam; Quality of Life; Antidepressive Agents; Recurrence; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37974160
DOI: 10.1186/s12888-023-05365-9 -
BMJ Open Aug 2023Studies finding perioperative hyperglycaemia is associated with adverse patient outcomes in surgical procedures spurred the development of blood glucose guidelines at...
PeRiOperative Glucose PRAgMatic (PROGRAM) trial protocol and statistical analysis plan for comparing automated intraoperative reminders to standardise insulin administration in surgical patients at high risk of hyperglycaemia.
INTRODUCTION
Studies finding perioperative hyperglycaemia is associated with adverse patient outcomes in surgical procedures spurred the development of blood glucose guidelines at many institutions. In this trial, we will assess the implementation of a clinical decision support tool that is integrated into the intraoperative portion of our electronic health record and provides real-time best practice recommendations for intraoperative insulin dosing in surgical patients at high risk for hyperglycaemia.
METHODS AND DESIGN
We will assess this intervention using a sequential and repeated cross-over design at the institutional level with periods of time for wash-out, control and study intervention. The unit of analysis will be the surgical case. The primary outcome will be the frequency of hyperglycaemia (>180 mg/dL (10 mmol/L)) at first postoperative anaesthesia care unit measurement. There are several prespecified secondary analyses focused on perioperative glycaemic control.
DISCUSSION
This protocol and statistical analysis plan describes the methodology, primary and secondary analyses. The PeRiOperative Glucose PRAgMatic (PROGRAM) trial was approved by the Vanderbilt University Institutional Review Board (IRB), Vanderbilt University Medical Center, Nashville, Tennessee, USA (IRB, 220991). The study results will be disseminated via publication in a peer-reviewed journal and presented at national scientific conferences. The results of PROGRAM trial will inform best practice for perioperative standardised insulin administration in surgical patients at high risk of hyperglycaemia.
TRIAL REGISTRATION NUMBER
NCT05426096.
Topics: Humans; Blood Glucose; Glucose; Hyperglycemia; Insulin; Patients; Cross-Over Studies
PubMed: 37620270
DOI: 10.1136/bmjopen-2023-072745 -
BMJ Open Aug 2023The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was 'Does treatment (with neurosurgery or stereotactic...
Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma - protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial.
INTRODUCTION
The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was 'Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?' This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT.
METHODS AND ANALYSIS
We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress.
ETHICS AND DISSEMINATION
This study was approved by the Yorkshire and The Humber-Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group.
TRIAL REGISTRATION NUMBER
ISRCTN41647111.
Topics: Adult; Child; Humans; Neurosurgery; Radiosurgery; Feasibility Studies; Pilot Projects; Brain; Randomized Controlled Trials as Topic
PubMed: 37558454
DOI: 10.1136/bmjopen-2023-075187 -
PloS One 2023Low-resourced settings often lack personnel and infrastructure for alcohol use disorder treatment. We culturally adapted a Brief Negotiational Interview (BNI) for... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Low-resourced settings often lack personnel and infrastructure for alcohol use disorder treatment. We culturally adapted a Brief Negotiational Interview (BNI) for Emergency Department injury patients, the "Punguza Pombe Kwa Afya Yako (PPKAY)" ("Reduce Alcohol For Your Health") in Tanzania. This study aimed to evaluate the feasibility of a pragmatic randomized adaptive controlled trial of the PPKAY intervention.
MATERIALS AND METHODS
This feasibility trial piloted a single-blind, parallel, adaptive, and multi-stage, block-randomized controlled trial, which will subsequently be used to determine the most effective intervention, with or without text message booster, to reduce alcohol use among injury patients. We reported our feasibility pilot study using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, with recruitment and retention rates being our primary and secondary outcomes. We enrolled adult patients seeking care for an acute injury at the Kilimanjaro Christian Medical Center in Tanzania if they (1) exhibited an Alcohol Use Disorder Identification Test (AUDIT) ≥8, (2) disclosed alcohol use prior to injury, or (3) had a breathalyzer ≥0.0 on arrival. Intervention arms were usual care (UC), PPKAY, PPKAY with standard text booster, or a PPKAY with a personalized text booster.
RESULTS
Overall, 181 patients were screened and 75 enrolled with 80% 6-week, 82.7% 3-month and 84% 6-month follow-up rates showing appropriate Reach and retention. Adoption measures showed an overwhelmingly positive patient acceptance with 100% of patients perceiving a positive impact on their behavior. The Implementation and trial processes were performed with high rates of PPKAY fidelity (76%) and SMS delivery (74%). Intervention nurses believed Maintenance and sustainability of this 30-minute, low-cost intervention and adaptive clinical trial were feasible.
CONCLUSIONS
Our intervention and trial design are feasible and acceptable, have evidence of good fidelity, and did not show problematic deviations in protocol. Results suggest support for undertaking a full trial to evaluate the effectiveness of the PPKAY, a nurse-driven BNI in a low-income country.
TRIAL REGISTRATION
Trial registration number NCT02828267. https://classic.clinicaltrials.gov/ct2/show/NCT02828267.
Topics: Adult; Humans; Alcoholism; Feasibility Studies; Pilot Projects; Tanzania; Single-Blind Method
PubMed: 37535693
DOI: 10.1371/journal.pone.0288458 -
Clinical Trials (London, England) Aug 2023There are unique opportunities related to the design and conduct of pragmatic trials embedded in health insurance plans, which have longitudinal data on member/patient...
BACKGROUND
There are unique opportunities related to the design and conduct of pragmatic trials embedded in health insurance plans, which have longitudinal data on member/patient demographics, dates of coverage, and reimbursed medical care, including prescription drug dispensings, vaccine administrations, behavioral healthcare encounters, and some laboratory results. Such trials can be large and efficient, using these data to identify trial-eligible patients and to ascertain outcomes.
METHODS
We use our experience primarily with the National Institutes of Health Pragmatic Trials Collaboratory Distributed Research Network, which comprises health plans that participate in the US Food & Drug Administration's Sentinel System, to describe lessons learned from the conduct and planning of embedded pragmatic trials.
RESULTS
Information is available for research on more than 75 million people with commercial or Medicare Advantage health plans. We describe three studies that have used or plan to use the Network, as well as a single health plan study, from which we glean our lessons learned.
CONCLUSIONS
Studies that are conducted in health plans provide much-needed evidence to drive clinically meaningful changes in care. However, there are many unique aspects of these trials that must be considered in the planning, implementation, and analytic phases. The type of trial best suited for studies embedded in health plans will be those that require large sample sizes, simple interventions that could be disseminated through health plans, and where data available to the health plan can be leveraged. These trials hold potential for substantial long-term impact on our ability to generate evidence to improve care and population health.
Topics: Aged; Humans; Medicare; National Institutes of Health (U.S.); Research Design; Sample Size; United States; Pragmatic Clinical Trials as Topic
PubMed: 37322894
DOI: 10.1177/17407745231160459 -
BMC Cardiovascular Disorders Sep 2023Cardiac rehabilitation (CR) improves outcomes in heart disease yet remains vastly underutilized. Remote CR enhanced with a digital health intervention (DHI) may offer...
BACKGROUND
Cardiac rehabilitation (CR) improves outcomes in heart disease yet remains vastly underutilized. Remote CR enhanced with a digital health intervention (DHI) may offer higher access and improved patient-centered outcomes over non-technology approaches. We sought to pragmatically determine whether offering a DHI improves CR access, cardiac risk profile, and patient-reported outcome measures.
METHODS
Adults referred to CR at a tertiary VA medical center between October 2017 and December 2021 were offered enrollment into a DHI alongside other CR modalities using shared decision-making. The DHI consisted of remote CR with a structured, 3-month home exercise program enhanced with multi-component coaching, a commercial smartphone app, and wearable activity tracker. We measured completion rates among DHI participants and evaluated changes in 6-min walk distance, cardiovascular risk factors, and patient-reported outcomes from pre- to post-intervention.
RESULTS
Among 1,643 patients referred to CR, 258 (16%) consented to the DHI where the mean age was 60 ± 9 years, 93% were male, and 48% were black. A majority (90%) of the DHI group completed the program. Over 3-months, significant improvements were seen in 6MWT (mean difference [MD] -29 m; 95% CI, 10 to 49; P < 0.01) and low-density lipoprotein cholesterol (MD -11 mg/dL; 95% CI, -17 to -5; P < 0.01), and the absolute proportion of patients who reported smoking decreased (10% vs 15%; MD, -5%; 95% CI, -8% to -2%; P < 0.01) among DHI participants with available data. No adverse events were reported.
CONCLUSIONS
The addition of a DHI-enhanced remote CR program was delivered in 16% of referred veterans and associated with improved CR access, markers of cardiovascular risk, and healthy behaviors in this real-world study. These findings support the continued implementation of DHIs for remote CR in real-world clinical settings.
TRIAL REGISTRATION
This trial was registered on ClinicalTrials.gov: NCT02791685 (07/06/2016).
Topics: Adult; Humans; Male; Middle Aged; Aged; Female; Cardiac Rehabilitation; Heart; Heart Diseases; Cholesterol, LDL; Patient-Centered Care
PubMed: 37700245
DOI: 10.1186/s12872-023-03471-w -
BMJ Open Jul 2023There are few empirically supported social and emotional well-being programmes for First Nations adolescents, and we found none targeting those living in Aboriginal...
INTRODUCTION
There are few empirically supported social and emotional well-being programmes for First Nations adolescents, and we found none targeting those living in Aboriginal communities in remote areas of Australia. The dearth of social and emotional well-being programmes is concerning given that adolescents in remote Australia are at much greater risk of mental disorder and suicide. Our pragmatic community-based research intervention 'Enabling Dads and Improving First Nations Adolescent Mental Health' is designed by and for First Nations people living in remote communities to promote and support the parenting role and examine the interconnection between men's parenting knowledge and adolescent mental health. The aim is to improve adolescent mental health by strengthening the participating father's empowerment, parenting confidence and engagement in the parenting role. The words Aboriginal, First Nation and Indigenous are applied interchangeably, as appropriate, throughout the article.
METHODS AND ANALYSIS
The intervention is currently being conducted in five remote First Nations communities in Far North Queensland, Australia. The project is funded by the Medical Research Future (MRFF UNSW RG200484), and staff recruitment and training began in early December 2020. The aim is to recruit 100 men and dyad adolescents, that is, in each of the five community sites, we will recruit 20 men and adolescent dyads at baseline. To date, we have complete data collection in one community, and fieldwork will begin in the final community in September 2023.The intervention involves a pragmatic randomised controlled trial, using a novel and culturally designed and manualised parenting programme with men (Strong Fathers, SF). The comparison group is receiving a culturally congruent and familiar yarning/relaxation (YR) condition. The SF component focuses on reinforcing knowledge related to parenting adolescents, promoting father's empowerment, and increasing their confidence and engagement with the adolescent. The second component systematically measures and examines differences in adolescent social and emotional well-being before and after their father's involvement in either the SF or YR. The adolescent is blind to the father's group allocation. The outcome measures for the men include parenting knowledge, attitudes and beliefs; a First Nations measure for empowerment; the Harvard Trauma Questionnaire (Indigenous) used to assess post-traumatic stress disorder symptoms; and alcohol use. The adolescent mental health outcomes are measured by a culturally congruent social and emotional well-being measure.
ETHICS AND DISSEMINATION
Ethics approval was granted from the Aboriginal Health and Medical Research Council of Australia: Human Research Ethics Committee (1711/20). Results will be verbally shared at community meetings and conferences, and reports will be produced for community stakeholder use. Data will be available for community-controlled health services and stakeholders. Findings will also be published in peer-reviewed journals, and summaries will be provided to the funders of the study as well as male participants and adolescents.
Topics: Adolescent; Humans; Male; Australia; Health Services, Indigenous; Mental Health; Australian Aboriginal and Torres Strait Islander Peoples; Fathers; Parenting; Adolescent Health; Pragmatic Clinical Trials as Topic
PubMed: 37407043
DOI: 10.1136/bmjopen-2023-072202