Trial Participants Research Articles

Representativeness of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trial participants

Underrepresentation by race and ethnicity in oncology clinical trials, including hematopoietic cell transplantation (HCT), is a known challenge. This analysis studied accrual on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials conducted in 2014-20 by race/ethnicity, age, and sex comparing these characteristics with those of potentially eligible patients identified from SEER and CIBMTR databases for the disease, age, and years of interest of BMT CTN studies. Five BMT CTN trials met inclusion criteria, including one autologous and four allogeneic HCT trials. Two studies focused on multiple myeloma (BMT CTN 1302 and 1401), two studies on graft versus host disease (GVHD) treatment (BMT CTN 1301 and 1501), and one study on post-HCT maintenance therapy in FLT3+ acute myelogenous leukemia (BMT CTN 1506). A decline in the proportion of patients from minority racial and ethnic groups was seen from the SEER population to trial enrollees, with the largest drop seen between the SEER population and all patients transplanted (on or off trial) in US transplant centers. Allogeneic HCT trials which allowed alternate donor graft sources had less decrease from the SEER population. No decrease was seen in clinical trial enrollment with respect to older age and female HCT recipients. This study provides insights into the underrepresentation of racial and ethnic minority patients in BMT CTN clinical trials, largely due to lack of access to HCT in general. Pathways expanding access to donors and improving the outreach of HCT programs to underserved populations are needed to improve access to clinical trials.

Impact of the COVID-19 pandemic on participants in pragmatic clinical trials for chronic pain: implications for trial outcomes and beyond

Impact of the COVID-19 pandemic on participants in pragmatic clinical trials for chronic pain: implications for trial outcomes and beyond

Reasons for acceptance or nonparticipation in iAdhere: a trial of latent TB infection treatment.

<sec><title>BACKGROUND</title>Understanding the motivations behind clinical trial participation can help enhance recruitment strategies and determine the generalizability of trial results. This study focuses on the reasons for participating in or declining the Tuberculosis Trials Consortium Study 33 (iAdhere), a clinical trial on the treatment of latent tuberculosis infection (LTBI).</sec><sec><title>METHODS</title>A quantitative evaluation was conducted among screened patients to ascertain their reasons for participating or not in the iAdhere trial. The study gathered data from enrolled participants and those who chose not to enroll.</sec><sec><title>RESULTS</title>Among 1,002 enrolled individuals, 290 participants provided 749 reasons for enrolling. The most common reasons included access to shorter treatment regimens (56%), avoiding progression to TB disease (45%), and improving health (21%). Of the 670 eligible persons who chose not to enroll, 551 individuals provided 800 reasons, with the most common being a preference for standard therapy (17%), disinterest in study medication or TB therapy (both 13%), and the inconvenience of daily observed treatment (12%).</sec><sec><title>CONCLUSION</title>The desire for shorter treatment options and preventing active disease motivates participation in LTBI trials. The diverse reasons for declining enrolment suggest the importance of developing targeted recruitment strategies. These findings support exploring shorter treatment regimens and can guide future recruitment efforts.</sec>.

The effect of BCG revaccination on the response to unrelated vaccines in urban Ugandan adolescents (POPVAC C): an open-label, randomised controlled trial

Immune responses induced by several important vaccines differ between populations, with reduced responses in low-income and rural settings compared with high-income and urban settings. BCG immunisation boosts immune responses to some unrelated vaccines in high-income populations. We aimed to test the hypothesis that BCG revaccination can enhance responses to unrelated vaccines in Ugandan schoolchildren. We conducted an open-label, randomised controlled trial to compare the effects of BCG revaccination versus no BCG revaccination on the immunogenicity of subsequent unrelated vaccines among adolescents aged 13-17 years who are participants in an urban Ugandan birth cohort study, in which BCG vaccination was documented at birth. Participants were excluded if they had received any of the trial vaccines or related agents when aged 5 years or older. Computer-generated 1:1 randomisation was implemented in REDCap. Participants were excluded if they were concurrently enrolled in other trials; had a clinically significant history of immunodeficiency, or serious psychiatric conditions or moderate to severe acute illnesses; were taking immunosuppressive medications; had allergies to vaccine components, a predisposition towards developing keloid scarring; positive HIV tests or pregnancy tests; were female participants who were lactating; or if they planned to use investigational drugs, vaccines, blood products, or any combination thereof. Trial participants assigned to the BCG revaccination group received the live parenteral BCG-Russia vaccine (Serum Institute of India, Pune, India; 0·1 mL intradermally, right upper arm) at week 0. All participants received yellow fever vaccine (YF-17D; Sanofi Pasteur, Lyon, France; 0·5 mL intramuscularly, left upper arm), live oral typhoid vaccine (Ty21a; PaxVax, London, UK; one capsule per day taken for three alternate days), and quadrivalent virus-like particle human papillomavirus (HPV) vaccine (Merck, Rahway, NJ, USA; 0·5 mL intramuscularly, left upper arm) at week 4; and toxoid vaccines (tetanus-diphtheria; Serum Institute of India; 0·5 mL intramuscularly, left upper arm) and an HPV booster at week 28. An additional HPV vaccination at week 8 was provided to female participants older than 14 years who had not previously been vaccinated. The primary outcomes were yellow fever neutralising antibody titres at 4 weeks post-YF-17D vaccination, Salmonella enterica serovar Typhi (henceforth S Typhi) O-lipopolysaccharide (O:LPS)-specific IgG concentration at 4 weeks post-Ty21a vaccination, and HPV-16 and HPV-18 L1 protein-specific IgG concentration at 4 weeks post-HPV vaccination. Primary outcome assays were conducted at week 8, and at week 52 for tetanus-diphtheria. We conducted an intention-to-treat analysis comparing log-transformed outcomes between trial groups, with results back-transformed to geometric mean ratios (GMRs). The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN10482904) and is complete. Between Aug 31 and Oct 12, 2020, we screened 376 potential participants for eligibility. We enrolled and randomly allocated 300 participants to the two groups (151 [50%] to the BCG group and 149 [50%] to the no BCG group). 178 (59%) of 300 participants were male and 122 (41%) were female. 142 (91%) of 151 participants in the BCG group and 139 (93%) of 149 in the no BCG group completed follow-up. There was no effect of BCG revaccination, compared with no BCG revaccination, on the response observed for any vaccine. Yellow fever plaque reduction neutralising reference tests (PRNT50) titres (the reciprocal of the last plasma dilution that reduced by 50%) had a GMR of 0·95 (95% CI 0·75-1·19; p=0·62) and PRNT90 (reciprocal of the last plasma dilution that reduced by 90%) had a GMR of 0·94 (0·74-1·19; p=0·60); IgG to S Typhi O:LPS was 0·99 (0·80-1·23; p=0·94); IgG to HPV-16 was 0·97 (0·69-1·35; p=0·85) and to HPV-18 was 1·03 (0·76-1·40; p=0·83); and toxoid-specific IgG for tetanus was 1·13 (0·87-1·47; p=0·36) and was 1·00 (0·87-1·16; p=0·97) for diphtheria. There were no serious adverse events in either group. We found no evidence that BCG revaccination is an effective strategy to improve immunogenicity of other vaccines in this low-income, urban setting. UK Medical Research Council. For the Luganda translation of the abstract see Supplementary Materials section.

Importance of tailored non-clinical safety testing of novel antimalarial drugs: Industry best-practice

Malaria is an acute, debilitating parasitic illness. There were 249 million cases of malaria in 2022, resulting in 608,000 deaths globally, 76% of which were children ≤5 years. The unique nature of this disease (recurrences leading to re-treatments and numerous organ systems affected), specific clinical treatment regimens, poor compliance, and diversity of affected populations (predominantly pediatrics, women of childbearing potential, pregnant and lactating women), often makes standard testing approaches inadequate, and tailor-made safety assessments are more appropriate.We provide best practice recommendations based on company experience for the non-clinical safety assessment of antimalarial drugs, with a focus on small molecules since they represent the majority of drug candidates for this illness. We focus on specific testing considerations for repeat dose toxicity studies, including combination toxicity assessments, since new drug treatment regimens typically foresee short treatment durations to improve compliance (i.e., 1 day) with combinations of compounds to improve efficacy and limit potential resistance. Due to the target population, the timing of reproductive, developmental, and juvenile toxicity studies may be earlier than general testing roadmaps for other small molecule drugs.In conclusion, key recommendations presented should enable a more effective and efficient development path whilst protecting clinical trial participants and patients.

Participant Diversity in Stroke‐Related Medical Device Trials: Historical Context and Ongoing Challenges

Despite an acknowledgment of the ethical and clinical importance of recruiting diverse populations into clinical trials, there is a continued underenrollment of patients with diverse demographic characteristics within the field of neurology and more specifically, in stroke‐related device trials. Efforts on the part of the US Congress, the National Institutes of Health, the US Food and Drug Administration, and the Centers for Medicare &amp; Medicaid Services over the past several decades have attempted to increase trial participant diversity with varying success. This historical context provides an important lens for analyzing diversity proposals and their bearing on device trials in the field of stroke neurology. Despite economic and logistical challenges, recruitment of appropriately diverse clinical trial populations through policy change and community engagement is critical to continuing to advance health equity goals.

Optimizing diversity, equity and inclusion in pragmatic clinical trials: Findings from the Pain Management Collaboratory

The National Institutes of Health, U.S. Department of Defense, and U.S. Department of Veterans Affairs established a Pain Management Collaboratory (PMC) in 2017, with the purpose of implementing and evaluating nonpharmacological approaches for management of pain and co-occurring conditions in military and veteran healthcare systems through the execution of pragmatic clinical trials. The purpose of the current study is to detail and critically examine recruitment and retention procedures across the PMC’s large-scale multi-site pragmatic clinical trials, with attention to efforts made by trialists to diversify their study samples. Team members from 11 pragmatic clinical trials completed semi-structured interviews that focused on the meaning of diversity to the trial teams when planning the composition of their samples, methods used to recruit and retain diverse samples of patients, and planned analyses that take into consideration diverse subgroups of patients. Nearly 18,000 patients have been enrolled across trials, 22 % of whom were assigned female sex at birth and 34 % of whom identify with a marginalized race or ethnicity. Respondents highlighted study site selection, formation of partnerships with patient groups, and leveraging of data informatics as strategies that aided in the recruitment of patients diverse in terms of birth sex, race, and ethnicity. Notably, trialists adopted a narrow definition of diversity that did not take into consideration multiple intersecting identities of trial participants. Based on experiences of the PMC, we provide 14 recommendations on ways to diversify patient samples in clinical pain research. PerspectiveThis article describes challenges posed, and opportunities provided, with pain pragmatic clinical trial designs, emphasizing approaches that optimize the inclusion of social identity groups that have historically been under-represented in pain research.

"Do it!" Gynecologic cancer clinical trial participants' advice to others and perspectives

"Do it!" Gynecologic cancer clinical trial participants' advice to others and perspectives

Commentary: On ‘Gender, Race, and Ethnicity in Lung Cancer Clinical Trial Participation’

Commentary: On ‘Gender, Race, and Ethnicity in Lung Cancer Clinical Trial Participation’

SOSIALISASI PENGEMBANGAN POTENSI WISATA PITKANO MENUJU DESA TUJUAN WISATA DI DESA SIBANGGEDE

Based on observations and field surveys in Sibanggede Village, Abiansemal District, Badung Regency has the potential for a tourist attraction, namely pitkano water sports, this tourist area uses the Tukad Ayung river path as a vehicle for pitkano activities. Pitkano Tourism is a means of promoting the Tourism Destination Village to attract tourists so as to grow the economy of the Sibannggede Traditional Village community. However, from the results of the interview, it was found that the management needs information related to the advantages and disadvantages along the pitkano route, this will affect the readiness of Sibanggede Village to become a tourist destination area (DTW) in the coming year. The efforts taken to solve these problems are to create the right media and means of socialization. This decision takes into account the cost aspect and the latest trends in public communication. Thus, it was decided that socialization would be carried out through the creation of adventure genre videos that would emphasize the main selling point of this potential for piccanoe tourism through the visual values of Tukad Ayung as a trial route as well as excitement or excitement in its implementation. And in addition to reviews of experiences from trial participants related to advantages or disadvantages during the activity.

The Implementation of the Advocacy Intervention for Midlife and Older Women Who Have Experienced Intimate Partner Violence: Protocol for a Randomized Controlled Trial.

Midlife and older women who experience intimate partner violence (IPV) often have less access to supports and services than younger women. There is far less focus on research and supports for midlife and older women compared to younger women experiencing IPV, and often, neither elder abuse nor IPV services meet their needs. Few interventions are available to meet the needs of midlife and older women. The goal of this randomized controlled trial is to test the effectiveness of an advocacy intervention for midlife and older women who experience IPV and to learn from the experiences of those who implement and participate in the program. This trial is a 2-arm, unblinded, parallel, pragmatic randomized controlled trial with a qualitative component. Eligible participants will be women who live in the Maritime provinces of Canada (New Brunswick, Nova Scotia, and Prince Edward Island), who are in midlife and older (aged approximately ≥50 years), and who are currently in a relationship with an abusive partner or have recently left an abusive partner. Facilitators will be trained to deliver the intervention. The intervention will be entirely virtual and will consist of 2 components: (1) an empowerment component, which will involve sharing resources and information with the women; and (2) a social support component, which will include providing support and encouragement to women for 12 weeks. Quantitative effectiveness data will be collected from all trial participants at baseline, 3 months after the intervention, and 9 months after the intervention about the incidence and severity of IPV, physical and mental health, and safety behaviors and strategies. Qualitative interviews will be conducted with the facilitators and intervention group participants. Control group participants will receive a static, nontailored version of the advocacy intervention for midlife and older women (AIM) intervention materials after baseline data collection. A total of 12 facilitators have been trained to deliver the AIM intervention to trial participants. Participant recruitment and data collection will be completed in January 2025. Data analysis will continue throughout the data collection period, and the results will be disseminated by December 2025. This research will result in the adaptation and testing of a program to support and empower midlife and older women in the Maritime provinces of Canada who experience IPV. International Standard Randomized Controlled Trial Registry ISRCTN30646991; https://doi.org/10.1186/ISRCTN30646991. DERR1-10.2196/57886.

Protocol for Surveying Participants and Professionals’ Experiences in an International Kidney Transplant Clinical Trial

Background Therapeutic misconception is a phenomenon in which participants or researchers misunderstand the nature and purpose of a clinical trial, believing that the primary goal of the trial is to provide them with individualized therapeutic benefit rather than to generate generalizable knowledge that will benefit future patients. Therefore, the perspectives of participants and researchers on these issues are central to improving the quality of health research to increase participant awareness and avoid therapeutic misconceptions. Objective The main objective of this study is to explore the views and experiences of patients and healthcare professionals regarding their participation in a clinical trial, the TTVguideIT randomized controlled trial, as part of the EU funded TTVguideTX project. The study was designed to identify therapeutic misconceptions of participants and health care professionals, assess their experiences with the informed consent process and their concerns regarding privacy and data protection. Methods This study is based on two distinct questionnaires, one intended for the professionals involved in the TTVguideIT clinical trial and the other for the patients. The questionnaires can be completed both online and on paper, allowing each individual to choose the format that suits them best. The questionnaires are written in the languages of the six participating countries, namely German, Spanish, French, Dutch, and Czech. Conclusion This study may help future research design and implementation to include participants' and professionals perspectives on the informed consent process and privacy and data protection, and aspects aimed at minimizing therapeutic misconceptions.

Understanding the barriers and enablers to participation in vaccine trials in a pregnant population from diverse ethnic background in an inner-city UK hospital.

Vaccination during pregnancy is an important healthcare intervention for safeguarding the health of the mother and their infants. Ethnic disparities in recruitment to vaccine research studies during pregnancy potentially contribute to health inequalities. The aim of the current study was to explore the barriers and enablers influencing the willingness of pregnant women from ethnic minority backgrounds to participate in vaccine research studies. Semi-structured qualitative online interviews were conducted with 23 pregnant women from diverse ethnic backgrounds in the UK. Interviews were transcribed verbatim, and thematically analysed. Our findings suggest that participants perceived vaccines and vaccine research, in principle, to be beneficial to the individual and to society, and understood the value of vaccination in mitigating severity of disease and protecting the health of mothers and their infants. Apprehension over the safety of vaccination in pregnancy was common and reduced willingness to participate. For those that decided to participate in vaccine trials in pregnancy, this was seen as an act of solidarity, a way to contribute to a collective responsibility for the public health of the community. Personal and community connections and representation-seeing people from their own communities represented in in the recruitment process shapped decisions about vaccine trial participating. Trust and mistrust in health systems, shaped by past experiences of interacting with healthcare professionals were likely to inform whether they would consider participating. Practical considerations such as excessive time commitments related to study procedures, travel and organising childcare were barrier to participation. The level of invasiveness of trial procedures were also a concern, although increased monitoring during the trial was seen as a potential benefit, mitigating some safety concerns. Our study reinforcing previously identified barriers to vaccine participation among pregnant women from diverse ethnic communities. This study underlines the need to develop tailored interventions that focus on fostering trust with the aid of community engagement to understand cultural contexts, establishing authentic representation, and address practical considerations, to contribute to enhancing vaccine trial participation in pregnancy in those from diverse ethnic communities.

Using QALYs as an Outcome for Assessing Global Prediction Accuracy in Diabetes Simulation Models.

(1) To demonstrate the use of quality-adjusted life-years (QALYs) as an outcome measure for comparing performance between simulation models and identifying the most accurate model for economic evaluation and health technology assessment. QALYs relate directly to decision making and combine mortality and diverse clinical events into a single measure using evidence-based weights that reflect population preferences. (2) To explore the usefulness of Q2, the proportional reduction in error, as a model performance metric and compare it with other metrics: mean squared error (MSE), mean absolute error, bias (mean residual), and R2. We simulated all EXSCEL trial participants (N = 14,729) using the UK Prospective Diabetes Study Outcomes Model software versions 1 (UKPDS-OM1) and 2 (UKPDS-OM2). The EXSCEL trial compared once-weekly exenatide with placebo (median 3.2-y follow-up). Default UKPDS-OM2 utilities were used to estimate undiscounted QALYs over the trial period based on the observed events and survival. These were compared with the QALYs predicted by UKPDS-OM1/2 for the same period. UKPDS-OM2 predicted patients' QALYs more accurately than UKPDS-OM1 did (MSE: 0.210 v. 0.253; Q2: 0.822 v. 0.786). UKPDS-OM2 underestimated QALYs by an average of 0.127 versus 0.150 for UKPDS-OM1. UKPDS-OM2 predictions were more accurate for mortality, myocardial infarction, and stroke, whereas UKPDS-OM1 better predicted blindness and heart disease. Q2 facilitated comparisons between subgroups and (unlike R2) was lower for biased predictors. Q2 for QALYs was useful for comparing global prediction accuracy (across all clinical events) of diabetes models. It could be used for model registries, choosing between simulation models for economic evaluation and evaluating the impact of recalibration. Similar methods could be used in other disease areas. Diabetes simulation models are currently validated by examining their ability to predict the incidence of individual events (e.g., myocardial infarction, stroke, amputation) or composite events (e.g., first major adverse cardiovascular event).We introduce Q2, the proportional reduction in error, as a measure that may be useful for evaluating and comparing the prediction accuracy of econometric or simulation models.We propose using the Q2 or mean squared error for QALYs as global measures of model prediction accuracy when comparing diabetes models' performance for health technology assessment; these can be used to select the most accurate simulation model for economic evaluation and to evaluate the impact of model recalibration in diabetes or other conditions.

Representation of Native Hawaiian and Pacific Islander Individuals in Clinical Trials

Having diverse participants in clinical trials ensures new drug products work well across different demographic groups, making health care safer and more effective for everyone. Information on the extent of Native Hawaiian and Pacific Islander participation in clinical trials is limited. To examine representation of Native Hawaiian and Pacific Islanders in clinical trials leading to the first US Food and Drug Administration (FDA) approvals for the 10 drug products with the top worldwide sales forecasts in 2024. Cross-sectional secondary analysis of existing data from clinical trials that took place from 2006 to 2021 in the US. All clinical trials that were included in the FDA first approval application for the 10 drug products were evaluated in this study. Data were analyzed from February to August 2024. Participation in a clinical drug trial. Comparison of the proportion of Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts in 2024 to the Native Hawaiian and Pacific Islander population proportion. In this cross-sectional study of 139 062 individuals, Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts was either unknown or low. For 6 of the 10 drug products (60%), the number of Native Hawaiian and Pacific Islander participants was not documented. All trials that reported Native Hawaiian and Pacific Islander participation had fewer Native Hawaiian and Pacific Islander participants than would be expected based on their US population proportion, with 2 of the differences being statistically significant. Of the trials that disaggregated Native Hawaiian and Pacific Islander participants from other racial groups, the number of Native Hawaiian and Pacific Islander participants was 8 for risankizumab-rzaa (0.38% of participants vs 0.49% of the population; percentage point difference, -0.11%; 95% CI, -0.37% to -0.15%), 7 for bictegravir/emtricitabine/tenofovir alafenamide (0.38% of participants vs 0.49% of the population; percentage point difference, -0.10%; 95% CI, -0.39% to 0.18%), 27 for 4vHPV/9vHPV (0.15% of participants vs 0.46% of the population; percentage point difference, -0.31%; 95% CI, -0.37% to -0.26%), and 90 for BNT162B2 COVID-19 vaccine (0.20% of participants vs 0.52% of the population; percentage point difference, -0.32; 95% CI, -0.36% to -0.27%). In this cross-sectional study, limited documentation and participation of Native Hawaiian and Pacific Islander individuals in clinical trials for drug products with top sales forecasts was found. This is especially concerning because Native Hawaiian and Pacific Islander individuals have a higher risk than other racial groups for type 2 diabetes, cancer, and several other conditions the products examined in this study treat. Given the importance of enrolling Native Hawaiian and Pacific Islander participants in clinical trials, sites should be established in key geographic regions, such as Hawai'i, and postmarket studies should be conducted within Native Hawaiian and Pacific Islander populations.

Recommendations to promote equity, diversity and inclusion in decentralized clinical trials.

Decentralized clinical trials involving the use of digital tools to facilitate remote research are gaining momentum. Rapid advancements in digital technologies have supported the adoption of these trials. These innovations facilitate virtual interactions between clinical trial teams and participants by making it easier to collect, transfer and store electronic data. While some studies have demonstrated the potential for these approaches to reduce barriers to clinical trial participation, they are associated with several challenges that may create or worsen existing health inequalities and limit the generalizability of trial results. Here we review the potential for digitally enabled and decentralized clinical trials to enhance clinical trial participation in an equitable manner. We describe the key barriers individuals from underserved groups may face, and provide recommendations to promote equity, diversity and inclusion.

Factors associated with non-publication of clinical trials in cardiovascular medicine: a cross-sectional analysis

Abstract Background/introduction Cardiovascular medicine is the fourth most-funded area of clinical research as it received an estimate for 7% of the total research funding. Nearly 8% of all clinical trials are cardiovascular-related (1,2). Non-publication of the registered clinical trials wastes money and time, encourages dissemination bias, and creates a body of possibly inaccurate literature, all of which obstruct scientific advancement. (3) Purpose To study the factors associated with the non-publication of cardiovascular clinical trials between January 2000 and June 2022. Methods We performed a cross-sectional analysis using ClinicalTrials.gov to determine all completed, discontinued, published, and unpublished cardiovascular medicine clinical trials between January 2000 and June 2022. For each trial, data on the trial phase, funding source, intervention type, enrolment size, trial completion, and publication status were extracted and subjected to logistic regression to determine clinical trial publication predictor factors. Results Among 3946 trials in cardiovascular medicine registered in ClinicalTrials.gov, there were 3215 completed trials included in the analysis. Of these, 34.2% (n=1100) were unpublished. On multivariate logistic regression, triple-blinded and quadruple-blinded trials were less likely to be unpublished compared to open-label trials (odds ratio [OR] 0.622; 95% confidence interval [CI] 0.45-0.85; p=0.003) and (OR 0.54; CI 0.42-0.69; p&amp;lt;0.001), respectively. Enrolment of 100 participants or more was associated with a decreased likelihood of non-publication (OR 0.46; CI 0.39-0.55; p&amp;lt;0.001). In addition, randomised trials were less likely to be unpublished than non-randomised trials (OR 0.67; CI 0.50-0.88; p=0.004). There was no significant effect of the intervention type, phase of the trial, trial participants' age and gender, or the trial funding resource on the publication status of cardiovascular medicine clinical trials. Conclusions It is observed that a considerable number of clinical trials in cardiovascular medicine remain unpublished. This issue raises some concerns regarding the risks and discomfort participants may encounter during the trial, while no results are added to the literature. Blinding of the trials, enrolment size, and allocation methods are the main predictors of trial publication.Forest plot of logistic regression

Real-world effectiveness of primary care psychological therapy for depression and anxiety in patients with coronary heart disease

Abstract Background Depression and anxiety are often inadequately treated in patients with coronary heart disease (CHD), despite mental health issues being associated with poorer quality of life, higher cardiovascular morbidity, and higher mortality. Talking therapies, such as cognitive behavioural therapy, are the recommended first-line treatment for depression and anxiety symptoms in CHD patients. However, the evidence for their effectiveness was considered low in a recent Cochrane review, and trial participants may not represent patients treated in routine clinical settings. Purpose To assess the effectiveness of routinely-delivered talking therapies in patients with CHD from nationwide primary care talking therapy services in England, and to compare their treatment outcomes to patients without a CHD diagnosis. Methods Healthcare records from 1.9 million patients who completed a course of treatment (≥2 treatment sessions) via NHS Talking Therapies for anxiety and depression (NHS TTad) between 2012-2019 were linked to Hospital Episode Statistics, the Mental Health Services Data Set, and death records. Standard NHS TTad outcome indicators (recovery, reliable improvement, and reliable deterioration) were examined in three groups, with (1) any CHD (n=41,317; ICD-10=I20-I25), (2) acute coronary syndromes (ACS, n=29,991; I21, I22, I20.0), and (3) chronic CHD (n=40,524; I20.1-I20.9, I23-I25) at baseline. Effect sizes for pre-post treatment changes in depression and anxiety symptom measures (PHQ-9 and GAD-7) were calculated using the adapted Cohen’s d for within-subjects design (dav). Outcomes were also compared to those of propensity-score matched control groups without the relevant diagnoses, using logistic regression. Results After completing a course of talking therapy, 49.8% (95%CI=49.3;50.3) of patients with CHD recovered from depression or anxiety, 69.4% (95%CI=69.0;69.9) saw reliable improvement in symptoms, and 7.3% (95%CI=7.0;7.5) experienced reliable deterioration in symptoms. There were large reductions in both depression (dav=-1.02) and anxiety symptoms (dav=-1.03) on average. Compared to a control sample of patients with no diagnosis of CHD, those with a CHD diagnosis were less likely to recover (OR=0.87[95%CI=0.84;0.89]) or reliably improve (OR=0.84[95%CI=0.81;0.87]) and more likely to reliably deteriorate (OR=1.28[95%CI=1.21;1.36]), when matched on age, sex, ethnicity, deprivation, baseline depression and anxiety symptom scores, self-reported long-term health condition, and waiting times between referral, assessment, and treatment. The findings were consistent for patients with ACS and those with chronic CHD. Conclusions Nearly half of CHD patients who received primary care talking therapy recovered, in line with the UK Government target of 50% recovery for the services. Nevertheless, compared to otherwise similar patients without CHD, those with CHD at baseline had worse psychological treatment outcomes.

A Process Evaluation in a Randomized Controlled Trial among Adults with Acetabular Dysplasia

Abstract Introduction The 2021 framework from the UK’s Medical Research Council defines evaluation as a theory-driven approach to examine how well an intervention works. However, the application of these guidelines can be challenging. Therefore, using a process evaluation case study on an exercise and patient education intervention for adults with acetabular dysplasia, we reflect on which specific aspects were relevant for the evaluation of the intervention and why. We focus on detailing methods to assess implementation (process, dose, reach), acceptability, mechanisms of change, and the impact of contextual factors. Methods Two hundred trial participants aged 18-50 years will be recruited from a University Hospital in Denmark and randomised to intervention and control groups. The process evaluation adopts a concurrent mixed-methods design involving self-report questionnaires at baseline and 6-month follow-up, training records and semi-structured focus groups with intervention providers (n = 10) and healthcare managers (n = 4-6). The mechanisms of change will be explored through semi-structured one-to-one interviews (at baseline and 6-month follow-up) with 15-20 purposefully sampled trial participants, and additionally, through exploratory examinations of associations between dose and change in health outcomes at 6-month follow-up), via simple linear regression models. The acceptability and contextual factors will be explored through one-to-one participant interviews, plus focus groups with 4-6 healthcare managers. Thematic analyses of the interviews will focus on expectations, experiences, events, personal understandings and interpersonal and organisational interactions. Conclusions The presentation will explore how the operational aspects of the intervention can be assessed through a process evaluation and how these findings may improve and expand any future implementation efforts.

Electronic nudge letters to increase influenza vaccination uptake in younger and middle-aged individuals with diabetes: a prespecified analysis of the NUDGE-FLU-CHRONIC trial

Abstract Background Despite evidence demonstrating that influenza vaccination is associated with reduced risk of adverse cardiovascular events and all-cause mortality, influenza vaccine uptake remains suboptimal in persons with diabetes mellitus (DM). Purpose In this prespecified analysis of the NUDGE-FLU-CHRONIC trial we assessed the effectiveness of electronically delivered nudges on influenza vaccine uptake according to DM status. Methods NUDGE-FLU-CHRONIC was a nationwide, randomized, pragmatic implementation trial among younger and middle-aged (18-64 years) Danish citizens with chronic disease during the 2023/2024 influenza season. All trial participants were eligible for a free influenza vaccination through the Danish governmental vaccine program. Participants were randomized in a 2.45:1:1:1:1:1:1 ratio to usual care (no electronic letter) or one of 6 different electronic nudge letters delivered on Sep 26, 2023. Baseline and outcome data were obtained using the Danish nationwide registries. The endpoint was receipt of a seasonal influenza vaccine on or before Jan 1, 2024. Results Of 299,881 NUDGE-FLU-CHRONIC participants, 57,666 (19.2%) had DM at baseline. Participants with DM had a median age of 51.6 years, 43.0% were female, median Hba1c of 53 mmol/mol, median DM duration of 10.0 years, and 51.2% were insulin dependent. During follow-up, 43.0% of those with DM vs. 34.6% of those without DM received the seasonal influenza vaccine (p&amp;lt;0.001). Any electronic letter vs. usual care was highly effective in increasing vaccine uptake in participants with DM at baseline (45.6% vs. 36.5%, difference: +9.1 percentage points [99.29%CI: 7.9-10.3], relative risk ratio [RR]: 1.42, 99.29%CI: [1.39-1.44]). However, DM status modified the effect of any electronic letter such that participants without DM at baseline experienced a slightly greater effect than those with DM (37.3% vs. 25.9%, difference: +12.3 percentage points [11.7-12.8], RR: 1.47 [1.45-1.50]; p-interaction &amp;lt;0.001). For each individual electronic nudge letter, the effect of the intervention was slightly lower in participants with DM compared to those without (Figure 1; all p-interaction &amp;lt; 0.015). When assessing DM subgroups, the effect of any electronic letter vs. usual care was greater in participants with DM and concomitant cardiovascular disease than in those without, greater in non-insulin treated than in insulin-treated individuals, and greater in those with shorter diabetes duration. Effectiveness of nudges were consistent across all other DM subgroups including HbA1c level (Figure 2). Conclusions Electronic nudge letters significantly boosted vaccine uptake in a broad range of individuals with DM, but the effect was slightly lower compared to those without DM. Future studies should test whether behaviorally designed nudges may positively influence other health behaviors in people with diabetes.