Electronic patient portals (PP) allow for targeted and efficient research recruitment. We assessed pre- and postnatal women's recruitment methods preferences, focusing on PP.

We conducted 4 in-person focus groups with new and expecting mothers. Participants reported demographics, health status, and comfort with technology including PP. We used descriptive statistics to characterize quantitative data and a quasi-deductive approach to analyze qualitative data.

Participants (n = 32) were an average age of 31.9 years, mostly White (65.6%), married (90.6%), and had a 4-year degree or higher (71.9%). Although they preferred PP for research recruitment over other methods (eg, in-person, physical mail), participants suggested potential barriers, including high message frequency, messages feeling like spam, and concerns about confidentiality. Participants suggested solutions, including enhancing autonomy through opt-in methods; integrating their healthcare provider's feedback; sending personal and relevant messages; and assuring their PP data are confidential.

PPs are a promising recruitment method for pre- and postnatal women including for maternal-child health studies. To ensure engagement with the method, researchers must respond to known patient concerns and incorporate their feedback into future efforts.

Although PP were generally viewed as an acceptable recruitment method, researchers should be mindful of barriers that may limit its reach and effectiveness.

Conducting clinical trials is resource demanding. Mirroring challenges experienced elsewhere, clinical trials conducted in Switzerland often face overoptimistic budget estimations and insufficient funding, leading to trial discontinuation and research waste. As a first step to address this problem, we investigated the current approaches to estimate clinical trial budgets in Switzerland.

We collected and examined the budgeting tools and approaches for clinical trials provided by the seven Swiss clinical trial units (CTUs) and the Swiss National Science Foundation (SNSF). We compared available approaches to the publicly accessible budgeting tool of the Belgian Health Care Knowledge Centre (KCE). For each approach, we collected data about user-testing, the availability of prespecified cost items, and estimates on cost ranges.

We found substantial heterogeneity in budget calculation approaches used by Swiss CTUs. None of the currently used tools and approaches provided by the seven CTUs or the SNSF was user-tested and neither supplied cost ranges for investigators to rely on. Five CTU tools included a detailed list of cost items. The SNSF provided a costing template with broad categories and is available for open grant applications only. One CTU tool was publicly available. The publicly available Belgian KCE tool was developed with user feedback and provided a detailed list of cost items, some cost ranges, and an instruction manual.

Stakeholders should consider improving budgeting practices in Switzerland by standardizing cost items and user-testing approaches. The continuously improved Belgian KCE tool could provide orientation.

The discontinuation and non-publication of clinical studies in various medical fields undermine research efforts and may bias the medical evidence base. This study investigates the prevalence and factors associated with these issues in endovascular stroke studies.

Clinical Trials.gov was searched for all studies registered from inception up till May 2022 and included patients with endovascular stroke. Publications from these studies were identified by extensive online searching using the NCT identifier number and other related keywords, and multiple logistic regression analysis was performed to identify characteristics associated with study discontinuation and non-publication.

Our search yielded 88 endovascular stroke studies, all including both genders. Among these, 63 (71.6 %) were completed, and 25 (28.4 %) were discontinued. Of the completed studies, 40 (63.5 %) were published. The majority of trials were single-centric (57 %), had a large sample size of >=100 (53.4 %), involved only adults (97.6 %), and were primarily funded by non-industrial sources (70 %). Discontinuation was more frequent in smaller-sized, single-center trials, but the associations diminished after adjustment. The sample size was a significant predictor of non-publication even after adjustment.

There is evidence of non-dissemination bias in clinical studies of endovascular stroke. These biases distort the therapeutic information available to inform clinical practice and raise ethical concerns regarding exposing volunteering participants to potential risks without furthering practice.

Online recruitment platforms are valuable tools that allow researchers to efficiently reach large pools of potential participants for clinical trials and observational studies. However, challenges associated with fraudulent respondents and bots threaten data credibility. This paper discusses signs we identified for recognizing potentially fraudulent respondents when using one online recruitment tool, ResearchMatch, to recruit study participants.

Participants were recruited via ResearchMatch for a study focused on stress and coping among U.S. young, low-income parents. Participants completed an online survey via Qualtrics. To screen for fraudulent respondents, we compared reports generated from Qualtrics with those from ResearchMatch.

We identified six signs of fraudulent respondents, including 1) suspicious metadata, 2) fake addresses listed in ResearchMatch profile, 3) a common Western name for both first and last names, 4) inconsistent and duplicate data, 5) extensive list of medications and/or medical conditions, and 6) short survey completion time. We contacted 63,284 accounts through ResearchMatch and received 928 survey responses. About 46 % (n = 425) of responses were deemed fraudulent.

Fraudulent respondents and bots undermine the integrity of data, which may result in adverse implications for research, policy, and patient health. Given that nearly half of the survey respondents in our study were deemed fraudulent, it is evident that this is a significant issue for recruiting research participants via online recruitment platforms. To ensure reliability and accuracy of study findings, it is critical for researchers to thoroughly examine their data for signs of fraudulence.

Overweight and obesity are chronic conditions with severe health implications, demanding effective and sustainable management strategies. The escalated Baduanjin, an adapted form of traditional Baduanjin, is proposed as a targeted intervention for individuals with overweight and obesity, offering a potentially effective and accessible approach to weight management and overall health improvement.

This pilot study aimed to assess the preliminary effects and feasibility of the online interactive escalated Baduanjin exercise program, with a focus on participant engagement and acceptance.

A 12-week pilot randomized controlled trial was conducted in Guangzhou, China, from June 30 to November 15, 2023, involving 50 participants with overweight and obesity. Participants were randomly allocated to the intervention group (n=26) or the control group (n=24). The intervention group received three 60-minute online interactive escalated Baduanjin exercises per week for 12 weeks, in addition to health education. The control group received only health education, delivered in three sessions over the 12-week period. The primary outcome was the change in body mass index (BMI) from baseline to week 12. Secondary outcomes included changes in waist circumference, body weight, blood glucose, lipid levels, blood pressure, quality of life, and dampness scale scores. Feasibility was assessed by participant adherence to the required intervention, and adverse events were recorded throughout the study period.

Compared to the control group, the intervention group exhibited a reduction in BMI (mean ± SD: -0.54 ± 1.67 vs. -0.13 ± 0.81), body weight, diastolic blood pressure, fasting blood glucose, and triglyceride levels over the 12 weeks, though this difference was not statistically significant. However, the intervention group demonstrated significant improvements in several health parameters, including waist circumference, fatigue scale-14 (FS-14), general anxiety disorder (GAD-7), patient health questionnaire-9 items (PHQ-9), Pittsburgh sleep quality index (PSQI), and dampness scale scores. Adherence to the intervention was high, with 82% (41/50) of participants completing the trial, and no serious adverse events were reported.

The preliminary effects and feasibility of the online interactive escalated Baduanjin for adults with overweight and obesity have been demonstrated, highlighting its potential multifaceted health benefits and high adherence.

https://www.chictr.org.cn, identifier ChiCTR2300072981.

The importance of publicly registering clinical trials and reporting their results in registries is widely recognised. While substantial progress has been made with registering trials before enrolment, the availability of results in registries remains uncommon despite expanding legislative and funder requirements-leading to an incomplete evidence base and avoidable waste of resources, particularly for unpublished trials. This paper discusses the rationale for reporting summary results in trial registries, reviews the current landscape of registry policies, and presents new WHO guidance for reporting results in registries. The 2025 WHO guidance was developed after consultation with relevant parties, including researchers, patients, sponsors, funders, regulators, journal editors, registry administrators, and the public. The guidance defines eight minimum items that are essential for understanding and interpreting the summary results for all trials. Implementation of the WHO guidance by trial registries, broad adherence by investigators and sponsors, and endorsement by funders, regulators, legislators, research ethics committees, patient organisations, and journals can help enhance the contribution of trials to scientific knowledge, patient care, and health policy.

Eczema is a prevalent, chronic, itchy skin condition that often persists into adulthood and significantly affects the quality of life of patients and their families. With no cure available at present, effective management is crucial. Although important patient priorities related to eczema self-management have been identified, they are rarely the focus of large, high-quality randomized controlled trials (RCTs).

To outline the methodology of using a citizen science approach to co-produce an online RCT on the frequency of bathing, to support the self-management of eczema.

The co-production of the trial with patients living with eczema involved research prioritization, intervention development and trial design, all carried out through a series of online meetings and surveys.

Co-producing the trial took 9 months, consisting of 13 online meetings (5 to prioritize the topic, 4 to develop the intervention and 4 to design the trial), requiring 39 h of time commitment from members of the public (n = 12) with a total spending of £5440 on reimbursements. A prioritization survey (n = 120) identified the most popular research question as how often to bath/shower, receiving 49% of votes. Following an iterative refinement among the co-production group members, the trial research question was formulated. The intervention development survey (n = 169) established current bathing practices and interest in participating in the trial. Survey results informed the development of study materials and influenced decisions related to trial design. The finalized study materials included key information about the target behaviour (weekly bathing or daily bathing), frequently asked questions and common concerns. The trial design co-production group determined the eligibility criteria, defined the intervention and comparator, selected the outcome measures, determined the study duration and developed the recruitment strategy. The Eczema Bathing Study opened to recruitment on 29 January 2024 and over 50% of the target sample size of 390 have been recruited within the first 2 months.

This paper provides a useful model for co-producing RCTs with members of the public. It describes the key stages of trial development (prioritization, intervention development, trial design) and contains information on the time and resources required to design trials using this approach.

In most randomized controlled trials (RCT), data is primarily and often only available for individuals who have agreed to be randomized, with little, if any, consideration for those who elected not to participate.

This study evaluated the value of including a concurrent observational cohort of patients who declined randomization in the Foraminotomy ACDF Cost-Effectiveness Trial (FACET-RCT) but still underwent anterior or posterior cervical surgery. The goal was to determine if the FACET-RCT results could be generalized by comparing baseline characteristics and clinical outcomes between the randomized trial and observational cohort.

A nationwide RCT with a parallel observational cohort recruiting patients from routine care.

Between January 2016 and May 2020, 389 patients with cervical radiculopathy were screened, and 358 were eligible. Of these, 265 (74%) were randomized in the FACET-RCT for either posterior or anterior cervical surgery, while 80 (22%) opted out of randomization and were followed in an observational cohort. Only 13 (4%) patients declined participation in both FACET-RCT and cohort.

Demographic data was collected, and primary outcomes included treatment success, evaluated using the Odom criteria as well as reduction in arm pain, assessed with a Visual Analogue Scale (VAS) at 6 weeks, and every 6 months up to 2 years postsurgery. Secondary outcomes included VAS for neck pain, neck disability, work ability, quality of life, treatment satisfaction, and need for revision surgeries.

Baseline characteristics were compared between the FACET-RCT and cohort using logistic regression. Primary and secondary outcomes were analyzed for differences between study designs using mixed-model analyses adjusted for confounders. The primary noninferiority endpoint of the FACET-RCT was evaluated in both the cohort and combined data from both cohort and FACET-RCT at 2 years of follow-up.

Patients in the cohort were slightly younger than those in the FACET-RCT (mean age of 48.4 versus 51.2 years; mean difference [MD], -2.5; 95% confidence interval [CI], -4.8 to -0.2; p=.04). In sub-analyses stratified by surgical approach (anterior vs. posterior surgery), fewer patients in the observational cohort who underwent posterior surgery reported severe neck pain at baseline compared to their counterparts in the FACET-RCT (OR, 0.38; 95% CI: 0.14 to 0.92; p=.04). No other significant baseline differences were found. No significant differences in treatment success (OR, 1.3; 95% CI: 0.3 to 6.0; p=.75) and arm pain reduction (MD, -3.9; 95% CI: -9.2 to 1.5; p=.16) were observed between study designs. The primary noninferiority endpoint was achieved in the combined data from both the cohort and FACET-RCT, with a narrower CI compared to the FACET-RCT alone, indicating a more robust result. Secondary outcomes were comparable between groups.

Randomization did not influence clinical outcomes for cervical surgery patients. Combining RCT with the observational cohort increased statistical power, external validity and robustness. Our findings support the value of observational methods as a complement to RCTs, especially when a large number of patients refuse RCT participation and high dropout and crossover rates are expected.

Insufficient patient accrual is a major challenge in clinical trials and can result in underpowered studies, as well as exposing study participants to toxicity and additional costs, with limited scientific benefit. Real-world data can provide external controls, but insufficient accrual affects all arms of a study, not just controls. Studies that used generative models to simulate more patients were limited in the accrual scenarios considered, replicability criteria, number of generative models, and number of clinical trials evaluated.

This study aimed to perform a comprehensive evaluation on the extent generative models can be used to simulate additional patients to compensate for insufficient accrual in clinical trials.

We performed a retrospective analysis using 10 datasets from 9 fully accrued, completed, and published cancer trials. For each trial, we removed the latest recruited patients (from 10% to 50%), trained a generative model on the remaining patients, and simulated additional patients to replace the removed ones using the generative model to augment the available data. We then replicated the published analysis on this augmented dataset to determine if the findings remained the same. Four different generative models were evaluated: sequential synthesis with decision trees, Bayesian network, generative adversarial network, and a variational autoencoder. These generative models were compared to sampling with replacement (ie, bootstrap) as a simple alternative. Replication of the published analyses used 4 metrics: decision agreement, estimate agreement, standardized difference, and CI overlap.

Sequential synthesis performed well on the 4 replication metrics for the removal of up to 40% of the last recruited patients (decision agreement: 88% to 100% across datasets, estimate agreement: 100%, cannot reject standardized difference null hypothesis: 100%, and CI overlap: 0.8-0.92). Sampling with replacement was the next most effective approach, with decision agreement varying from 78% to 89% across all datasets. There was no evidence of a monotonic relationship in the estimated effect size with recruitment order across these studies. This suggests that patients recruited earlier in a trial were not systematically different than those recruited later, at least partially explaining why generative models trained on early data can effectively simulate patients recruited later in a trial. The fidelity of the generated data relative to the training data on the Hellinger distance was high in all cases.

For an oncology study with insufficient accrual with as few as 60% of target recruitment, sequential synthesis can enable the simulation of the full dataset had the study continued accruing patients and can be an alternative to drawing conclusions from an underpowered study. These results provide evidence demonstrating the potential for generative models to rescue poorly accruing clinical trials, but additional studies are needed to confirm these findings and to generalize them for other diseases.

Poor recruitment is one key reason for premature closure of randomised controlled trials. The Melatonin for Anxiety prior to General Anaesthesia In Children (MAGIC) trial was a multicentre randomised controlled trial of melatonin vs midazolam in the premedication of anxious children, before surgery. The trial ran between 2019 and 2022, closing early because of recruitment futility. This paper describes the challenges that arose during the trial and offers recommendations for the design of future perioperative trials.

A case-based approach was used to identify barriers to recruitment. As part of a qualitative sub-study, semi-structured interviews with local site teams, participants, and caregivers also explored barriers and enablers to recruitment.

Issues encountered included time sensitivity within pressured environments; feasibility of paediatric assent; research pharmacy availability; variation in anaesthetist equipoise; multifactorial decision-making issues in premedication selection; and the Associate Principal Investigator scheme being unable to support trials within anaesthetic trainee rotations. Future paediatric perioperative medicine trials could consider funding for research pharmacy outside of working hours; conducting risk assessments for study drugs to be held on theatre admission units; and a tailored design of site feasibility assessments to help address variation in practice. Challenges remain for the feasibility of including anaesthetic trainees within the Associate Principal Investigator scheme structure.

There are significant challenges to recruitment for paediatric clinical trials in anaesthesia and perioperative medicine. The MAGIC trial highlighted variations within anaesthetic practice at individual, local, and regional levels. Lessons learned from the MAGIC trial identifies specific barriers to paediatric trial enrolment, offer solutions and discusses ongoing challenges.

ISRCTN registry: ISRCTN18296119.

The successful conduct of health and medical research is largely dependent on participant recruitment. Effective, yet inexpensive methods of increasing response rates for all types of research are required. QR codes are now commonplace, and despite having been extensively used to recruit study participants, a search of the literature failed to reveal any randomized trial investigating the effect of adding a QR code on qualitative research response rates.

This study aimed to collect data on rates of response, consent, and decline among patients with cancer, and the average time taken to respond following randomization to receive either a QR code or no QR code on the patient consent form for a qualitative research study.

This was a pilot randomized controlled trial (RCT) embedded within a qualitative research study. In total, 40 eligible patients received a recruitment pack for the qualitative study, which included an information statement, a consent form, and an addressed, stamped envelope to return their consent form. Patients were randomized 1:1 to the control (standard recruitment pack only) or intervention group (standard recruitment pack including modified consent form with a QR code).

In total, 27 out of 40 patients (age: mean 63.0, SD 14.8 years; 45% female) responded to the consent form. A lower proportion of the QR code group (60%) responded (odd ratio [OR] 0.57, 95% CI 0.14-2.37; P=.44), compared to 75% of the standard recruitment group. However, a higher proportion of the QR group (35%) consented (OR 1.84, 95% CI 0.41-8.29; P=.43), compared to the standard recruitment group (20%). A lower proportion of the QR group (25%) declined (OR 0.34, 95% CI 0.09-1.38; P=.13) relative to the standard recruitment group (55%). The mean response time of the QR code group was 16 days (rate ratio [RR] 0.79, 95% CI 0.47-1.35; P=.39) compared to 19 days for the standard recruitment group. None of the age-adjusted analyses were statistically significant.

This underpowered pilot study did not find any evidence that offering an option to respond through a QR code on a patient consent form for a qualitative study increased the overall patient response rate (combined rate of consent and decline). However, there was a nonsignificant trend, indicating that more patients who received the QR code consented compared to those who did not receive the QR code. This study provides useful preliminary data on the potential impact of QR codes on patient response rates to invitations to participate in qualitative research and can be used to inform fully powered RCTs.

OSF Registries 10.17605/OSF.IO/PJ25X; https://doi.org/10.17605/OSF.IO/PJ25X.

Chronic illness research has many challenges making research recruitment difficult. Despite reports of facilitators and barriers to research recruitment challenges remain. The reporting of research strategies and their impact on recruitment and subsequent randomised control trials is not sufficient. A newly developed chronic illness research recruitment taxonomy (CIRRT) details factors and elements observed to impact recruitment around the components of Project, People, and Place. This paper aims to use the chronic illness research recruitment taxonomy to report and evaluate the recruitment strategies, impact they had on recruitment, and alterations to an eHealth feasibility study.

Retrospective mixed method approach was used to inductively code the research team meeting minutes during the recruitment period. The coding was then abductively matched to the chronic illness research recruitment taxonomy and gaps in the CIRRT noted. Dated coding data were integrated with recruitment progress to explore the impact of research recruitment strategies.

Meeting minutes (n = 66) were analysed, recruitment strategies identified and matched to CIRRT. The reporting and identification of the recruitment strategies was aided by CIRRT use. By integrating the codes that aligned with CIRRT with recruitment progress was observed to be impacted by staffing and researcher visits.

CIRRT may be a useful tool in the evaluation and reporting of research recruitment strategies. Altering the roles of nurses involved and researcher visits to recruiting sites may positively impact on chronic illness research recruitment.

A substantial proportion of anorexia nervosa patients require intensive treatments, commonly inpatient or day-patient treatment. The relative merits of these treatments for adults with anorexia nervosa are unknown. Therefore, a trial investigating the clinical effectiveness and cost-effectiveness of inpatient treatment-as-usual versus a stepped-care day-patient approach in adults with anorexia nervosa (DAISIES) was commissioned. This trial terminated prematurely due to poor recruitment, mainly resulting from COVID-19's impact on service provision.

We describe the rationale, methods and available outcomes of the DAISIES trial. Reasons behind the trial's failure and implications for future research are investigated.

A two-arm multicentre open-label parallel-group non-inferiority randomised controlled trial, evaluating the effectiveness, acceptability and cost-effectiveness of two intensive treatments for adults with severe anorexia nervosa.

Specialist eating-disorder services in the United Kingdom with inpatient and/or day-patient treatment facilities.

Adults (age 17 +) with severe anorexia nervosa (body mass index ≤ 16 kg/m2) requiring intensive treatment and (optionally) their carers. Intended sample size: 386.

Inpatient treatment-as-usual and a stepped-care day-patient treatment approach (with the option of initial inpatient treatment for medical stabilisation).

The primary outcome was body mass index at 12 months post randomisation. Qualitative interviews conducted during the trial included semistructured interviews to investigate patients', families' and clinicians' views on treatments.

During the 16-month recruitment period (November 2020 to March 2022), 53 patients were approached. Of these, 15 were enrolled and randomly allocated to the inpatient treatment-as-usual (n = 7) or day-patient treatment (n = 8) treatment arms. All participants were female with a mean (standard deviation) age of 24.8 (9.1) years and a mean (standard deviation) body mass index of 14.4 (1.6) kg/m2. Patients' body mass indexes had increased similarly in both groups at 12 months. Participants perceived the stepped-care day-patient treatment approach to be more acceptable than inpatient treatment-as-usual. Qualitative interviews with patients, carers and clinicians suggested valued (e.g. multidisciplinary provision of care) and disliked (e.g. perceived over-focus on weight gain) aspects of treatment. Investigation of the reasons behind the trial's failure revealed strong treatment preferences among patients as the most common reason for non-participation, alongside the impact of COVID-19 on service provision.

The main trial questions could not be answered due to low participant numbers.

No conclusions can be drawn concerning the clinical and cost-effectiveness of inpatient treatment-as-usual or stepped-care day-patient treatment. The day-patient treatment approach was perceived more positively by patients and carers. Service-related (e.g. reduced clinician time for research), patient-related (e.g. treatment preferences) and wider systemic factors (e.g. reduced service capacity and patient throughput nationally during COVID-19) seem to have contributed to the failure of the DAISIES trial.

Despite the trial's failure, the need to investigate the effectiveness and experience of intensive treatments of adult anorexia nervosa remains. Alternative trial designs incorporating patient preferences and investigating community-based intensive treatment options have potential to improve acceptability and recruitment.

This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number HTA 17/123/03.

We aim to assess which variables are associated with recruitment failure of obstetrical and gynaecological randomised controlled trials (RCTs), leading to an extension of the study period.

Nationwide study.

A cohort of RCTs supported by the trial centre of the Dutch Consortium of Obstetrics and Gynaecology.

We included 83 RCTs that recruited patients between 1 March 2003 and 1 December 2023.

Main outcome was recruitment target not achieved within 6 months after the preplanned recruitment period. Secondary outcomes were recruitment target not achieved within an extension period of at least 12 months and premature termination of the trial. In all RCTs, we collected information on variables with a potential effect on recruitment failure, recorded at five levels; patient, doctor, participating centre, study organisation and study design.

In total, 46 of 83 RCTs (55%) did not achieve their targeted recruitment within the preplanned study period with a maximal extension period of 6 months. The most relevant variables for recruitment failure in multivariable risk prediction modelling were presence of a no-treatment arm (where treatment is standard clinical practice), a compensation fee of less than €200 per included patient, funding of less than €350 000, while a preceding pilot study lowered this risk.

We identified that the presence of a no-treatment arm, low funding and a low compensation fee per included patient were the most relevant risk factors for recruitment failure within the preplanned period, while a preceding pilot study lowered this risk. Awareness of these variables is important when designing future studies.

The timely enrollment of study participants is critical to the success of clinical trials. Understanding factors that contribute to patients' decision to participate in trials involving online cognitive behavioural therapy for pain management should prove helpful to optimize the design of study protocols. Fracture patients from an orthopaedic clinic who declined to participate in the Cognitive behavioural therapy to Optimize Post-operative rEcovery (COPE) trial were asked to complete a Research Participation Questionnaire that asked them about their previous experiences with clinical research and mental health therapy and their reasons for declining to participate in the COPE trial. At the end of the questionnaire, a subset of participants was offered the opportunity to participate in a telephone interview to further discuss why they declined to participate in the COPE trial. Sixty-four patients who declined to participate in the COPE trial completed the questionnaire and twenty of these participants agreed to take part in a telephone interview (31%). Twenty-two participants (34%) had previous experience with clinical research and six participants (9%) had received cognitive behavioural therapy (CBT) in the past. Excessive time commitment (41%) was the most commonly selected reason for not participating in the COPE trial, followed by a disinclination to participate in clinical research (19%). Four themes emerged from the interviews with participants: 1) belief that they could overcome mental health challenges after their fracture without external help; 2) belief that CBT might be helpful for some fracture patients, but not for themselves; 3) preference for online or in-person CBT; and 4) concerns regarding time commitment. To maximize enrollment, trials exploring the role of psychotherapy in recovery from orthopedic trauma should optimize time commitment of psychotherapy. Providing information in the patient consent process regarding evidence for psychotherapy and recovery from orthopedic trauma may also prove helpful in promoting patient enrollment.

Understanding site-related factors that influence enrolment within multicenter randomized controlled trials (RCT) may help reduce trial delays and cost over-runs and prevent early trial discontinuation. In this analysis of PROSPECT (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial), we describe patient enrolment patterns and examine factors influencing site-based monthly enrolment.

Retrospective analysis of a multicenter RCT.

The PROSPECT multicenter RCT enrolled patients in the main trial from July 2015 to March 2019. We documented site characteristics and trial metrics including data from the methods center tracking documents, site-level data at trial initiation, screening logs submitted by research coordinators, and prospectively collected case report forms. In this retrospective analysis of trial data, we analyzed enrolment patterns across sites using negative binomial regression to explore the association between monthly enrolment rate accounting for number of ICU beds, site characteristics, and trial metrics.

Overall, 41 sites enrolling 2365 patients in the PROSPECT main trial were analyzed. After accounting for number of beds in each ICU, site launch early in the trial was associated with higher monthly enrolment rates, but time to first enrolment and research coordinator experience was not. We observed considerable variability in the number of active screening months and enrolment rates across sites.

These findings highlight the complexity of recruitment dynamics in critical care RCTs and emphasize the need for tailored approaches to trial planning and execution.

PROSPECT (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial): NCT02462590 (registered June 2, 2015).

While patient and public involvement (PPI) in clinical research contributes substantially to research ethics, feasibility and quality, the uptake and implementation of PPI-based approaches in Switzerland remain unknown. This study aimed to evaluate the current state and acceptance of PPI in academic clinical research in Switzerland, with the goal of developing recommendations for its future implementation and development.

A sequential explanatory mixed-methods study was conducted to assess the current landscape and acceptance of PPI in academic clinical research across different stakeholder groups in Switzerland. The groups were "Patients and Public", "Researchers", "Staff Members of Academic Research Infrastructure (ARI)" and representatives from "Regulatory and Funding Bodies". Data was collected through a combination of surveys and semi-structured interviews. The survey results were analysed descriptively, while interview data was analysed qualitatively. The results were further synthesised into a SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis.

 A total of 123 survey responses were collected.Surveys revealed great support and acceptance for PPI in academic clinical research in Switzerland across all stakeholder groups. Despite this support, several challenges were identified, including gaps in training, limited funding opportunities and insufficient infrastructure to facilitate PPI.

The current framework for PPI in Switzerland is in an early stage of development. A joint effort by all stakeholders is needed to catch up with international progress to reach high-level ethical and quality standards. A basic framework for PPI in academic clinical research in Switzerland should be implemented, including guidelines for qualification and collaboration, best practices as well as widespread information for patients, the public and researchers. Further needed are training opportunities in "PPI in clinical research" for all stakeholders as well as sustainable sources of funding.

Conducting high-quality randomized clinical trials (RCTs) is challenging and resource intensive. Funders and academic investigators depend on limited financial resources and, therefore, need empirical data for optimal budget planning. However, current literature lacks detailed empirical data on resource use and costs of investigator-sponsored RCTs. The aim of this study is to systematically collect cost data from investigator-sponsored RCTs from Switzerland, Germany, and the United Kingdom (UK).

Principal investigators were asked to share their RCT cost and resource use data and enter it into an online case report form. We assessed cost patterns, cost drivers, and specific cost items, examined costs by study phase (planning-, conduct-, and finalization phase), compared planned with actual RCT costs, and explored differences in cost patterns across countries, medical fields, and intervention types.

We included 93 RCTs which were initiated in Switzerland (n = 53; including eight conducted in low- and lower middle-income countries), Germany (n = 22), and the UK (n = 18). The median total trial cost in our RCT sample was $645,824 [interquartile range (IQR), $269,846-$1,577,924]. The median proportion of the total costs spent for planning phase was 27.5% [IQR, 20.6%-39.7%], for conduct phase 57.3% [IQR, 44.4%-66.3%], and for finalization phase 12.7% [IQR, 8.5%-19.3%] with little variation across countries. The items that contributed most to the total costs were protocol writing (7.2%; IQR 3.8%-10.6%), data management (5.0%; IQR 2.2%-8.1%) and follow-up (4.5%; IQR 2.3%-8.4%). Of the 66 RCTs with an available original budget, 46 (69.7%) exceeded the budget by over 50%. Use of routinely collected data to assess primary outcomes was independently associated with lower per patient- and lower total trial costs.

Over a quarter of total trial costs were incurred in the planning phase, which is typically not fully funded. Two-thirds of RCTs exceeded their budget by more than 50%. Investigators and funders should consider empirical cost data to improve budgeting and funding practices.

Researchers conducting trials have a responsibility to publish the results of their work in a peer-reviewed journal, and failure to do so may introduce bias that affects the accuracy of available evidence. Moreover, failure to publish results constitutes research waste.

To systematically review research reports that followed clinical trials from their inception and their investigated publication rates and time to publication. We also aimed to assess whether certain factors influenced publication and time to publication.

We identified studies by searching MEDLINE, Embase, Epistemonikos, the Cochrane Methodology Register (CMR) and the database of the US Agency for Healthcare Research and Quality (AHRQ), from inception to 23 August 2023. We also checked reference lists of relevant studies and contacted experts in the field for any additional studies.

Studies were eligible if they tracked the publication of a cohort of clinical trials and contained analyses of any aspect of the publication rate or time to publication of these trials.

Two review authors performed data extraction independently. We extracted data on the prevalence of publication and the time from the trial start date or completion date to publication. We also extracted data from the clinical trials included in the research reports, including country of the study's first author, area of health care, means by which the publication status of these trials were sought and the risk of bias in the trials.

A total of 204 research reports tracking 165,135 trials met the inclusion criteria. Just over half (53%) of these trials were published in full. The median time to publication was approximately 4.8 years from the enrolment of the first trial participant and 2.1 years from the trial completion date. Trials with positive results (i.e. statistically significant results favouring the experimental arm) were more likely to be published than those with negative or null results (OR 2.69, 95% CI 2.02 to 3.60; 19 studies), and they were published in a shorter time (adjusted HR 1.92, 95% CI 1.51 to 2.45; 4 studies). On average, trials with positive results took 2 years to publish, whereas trials with negative or null results took 2.6 years. Large trials were more likely to be published than smaller ones (adjusted OR 1.92, 95% CI 1.33 to 2.77; 11 studies), and they were published in a shorter time (adjusted HR 1.41, 95% CI 1.18 to 1.68; 7 studies). Multicentre trials were more likely to be published than single-centre trials (adjusted OR 1.20, 95% CI 1.03 to 1.40; 2 studies). We found no difference between multicentre and single-centre trials in time to publication. Trials funded by non-industry sources (e.g.governments or universities) were more likely to be published than trials funded by industry (e.g. pharmaceutical companies or for-profit organisations) (adjusted OR 2.13, 95% CI 1.82 to 2.49; 14 studies); they were also published in a shorter time (adjusted HR 1.46, 95% CI 1.15 to 1.86; 7 studies).

Our updated review shows that trial publication is poor, with only half of all trials that are conducted being published. Factors that may make publication more likely and lead to faster publication are positive results, large sample size and being funded by non-industry sources. Differences in publication rates result in publication bias and time-lag bias that may influence findings and therefore ultimately affect treatment decisions. Systematic review authors should consider the possibility of time-lag bias when conducting a systematic review, especially when updating their review.

This Cochrane review had no dedicated funding.

This review combines and updates two earlier Cochrane reviews. The two protocols and previous versions of the two updated reviews are available via 10.1002/14651858.MR000006 and 10.1002/14651858.MR000006.pub3 and 10.1002/14651858.MR000011 and 10.1002/14651858.MR000011.pub2.

Clinical research is marked by its multifaceted nature, presenting a multitude of different approaches, designs, and objectives that can complicate the planning, initiation, and conduct of clinical trials. The role and organisation of the sponsor institution are pivotal in this context. We aimed to investigate possible challenges and needs, including their underlying factors, for academia and industry during the set-up and conduct of clinical trials.

We conducted a cross-sectional survey-based study within an international network of highly qualified academic research institutions (ARIs). The main outcome measures were the regulatory framework for clinical trials, scope and organisation of academic and industry-sponsored trials, funding sources of academic clinical trials, submission and approval process, as well as study conduct of academic vs. industry-sponsored trials.

We surveyed employees of ARIs with extensive experience in phase I-IV clinical trials. All ARIs participated in academic clinical trials and 90% were involved in industry-sponsored trials. Respondents reported that academic trials faced greater challenges in communication with relevant institutional review boards/ethics committees and competent authorities compared to industry-sponsored trials. Additionally, academic trials were found to have significantly less financial support during their conduct. Specific challenges for academia vs. industry included 'insufficient personnel resources' (60% vs. 50%), 'recruitment problems' (60% vs. 78%) and 'lack of knowledge/experience' (35% vs. 11%).

Our findings indicate that industry-sponsored trials encounter fewer issues in set-up, funding, and trial conduct compared to academic trials. Improving collaboration between academic sponsors and ARIs is essential to address these challenges. ARIs provide critical support and guidance for academic researchers, not only in planning and implementing projects, but also in assessing feasibility and securing funding.

Early in the COVID-19 pandemic, numerous clinical trials were initiated. Although concerns were raised regarding the quality of the trials, the eventual research output yielded from the trials remains unknown. The objective of this study was to include all clinical trials registered on ClinicalTrials.gov during the first 6 months of the pandemic and assess if and where their results had been reported, their completion and discontinuation rates, achieved enrolment and changes made to the primary outcome after trial registration.

We included all interventional studies related to COVID-19 first registered on ClinicalTrials.gov between 1 January 2020 and 1 July 2020. We systematically searched for trial results, reported through 15 May 2023, in scientific publications, preprints and ClinicalTrials.gov. We assessed the achieved trial enrolment, trial discontinuation (reaching <90% of target enrolment), and whether the primary outcome had been changed as compared with the initial protocol registration.

The 775 clinical trials included in the analysis planned to enrol 238 933 (median (IQR) 120 (60, 304) patients; 355 (46%) of the trials had reported results, and 283 (36%) were published in a scientific journal. In the reported trials, the total enrolment was 95 332 (median (IQR) 105 (45, 222) patients. 186 (24%) trials were completed, and 169 (22%) trials were discontinued, with slow recruitment being the most stated reason for discontinuation (9% of all trials, although 30% of the discontinued trials did not report a reason). 117 (33%) of the reported trials had changed their primary outcome. In total, 157 (20%) trials were completed and published in a scientific journal, of which 105 enrolled ≥100 patients and 103 had not changed the primary outcome. 63 completed and published trials enrolled ≥100 patients and had not changed the primary outcome.

Most clinical trials of COVID-19 registered at ClinicalTrials.gov during the first 6 months of the pandemic remained unreported or had been discontinued. Many of the trials whose results had been reported enrolled few patients and changed the primary outcome after trial registration.

Research waste is a considerable problem in clinical trials, with nonpublication being a significant contributor. We aimed to determine the prevalence of discontinuation and nonpublication of randomized controlled trials (RCTs) on cervical cancer or precancer.

We searched ClinicalTrials.gov for registered RCTs investigating cervical cancer or precancer that started between January 2000 and December 2020. The primary and secondary outcomes were trial nonpublication and premature discontinuation, respectively. Publication status was determined by systematic searches of peer-reviewed journals using the PubMed and Scopus databases.

A total of 113 RCTs met the inclusion criteria. Among the 85 trials completed before December 2020, 44 (51.8%) were prematurely discontinued and 40 (47.1%) were unpublished. A single-center design (61.4% vs. 34.1%, P = .012) and lack of external funding (59.1% vs. 36.6%, P = .038) were significantly associated with trial discontinuation. Large-scale (target sample size >400; 46.7% vs. 17.5%, P = .004) and externally funded trials (66.7% vs. 35.0%, P = .004) were more likely to be published. Multivariate logistic analysis revealed that a large sample size [odd ratio (OR): 4.125, 95% confidence interval (CI): 1.511-11.259, P = .006] and presence of external funding (OR: 3.714, 95% CI: 1.513-9.117, P = .004) were independent positive factors for trial publication.

A significant proportion of RCTs related to cervical cancer or precancer were discontinued early or remain unpublished, resulting in a waste of research resources.

Efficient evidence generation to assess the clinical and economic impact of medical therapies is critical amid rising healthcare costs and aging populations. However, drug development and clinical trials remain far too expensive and inefficient for all stakeholders. On October 25-26, 2023, the Duke Clinical Research Institute brought together leaders from academia, industry, government agencies, patient advocacy, and nonprofit organizations to explore how different entities and influencers in drug development and healthcare can realign incentive structures to efficiently accelerate evidence generation that addresses the highest public health needs. Prominent themes surfaced, including competing research priorities and incentives, inadequate representation of patient population in clinical trials, opportunities to better leverage existing technology and infrastructure in trial design, and a need for heightened transparency and accountability in research practices. The group determined that together these elements contribute to an inefficient and costly clinical research enterprise, amplifying disparities in population health and sustaining gaps in evidence that impede advancements in equitable healthcare delivery and outcomes. The goal of addressing the identified challenges is to ultimately make clinical trials faster, more inclusive, and more efficient across diverse communities and settings.

Conducting high-quality randomized clinical trials (RCTs) is challenging, time consuming, and resource intense. Academic investigators usually depend on scarce financial resources; however, current literature lacks systematically collected empirical data on the detailed resource use and costs of investigator-initiated RCTs.

The aim of this study is to generate a database of detailed empirical resource use and cost data from 100 investigator-initiated RCTs in Switzerland, Germany, and the UK. Investigators enter their empirical costs data into an online data collection form, which is followed by a short interview and a detailed cost report. We plan to investigate cost patterns and cost drivers and examine planned versus actual RCT costs as well as explore different strata of costs across the planning, conduct, and finalization phases, in drug and non-drug trials, and across medical fields and countries.

This study will add detailed empirical data to the limited research on investigator-initiated RCT costs currently available. A study limitation will be that cost data will be retrospective and self-reported, which might be inaccurate depending on how costs were recorded.

Open Science Framework (OSF) https://doi.org/10.17605/OSF.IO/QY2GU . Registered on June 4, 2021.

Treatment decisions for persons with relapsing-remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease-modifying therapy treatments targeting no evidence of disease activity, while achieving better patient-relevant outcomes, fewer adverse events, and improved care. Serum neurofilament light chain (sNfL) is a sensitive measure of disease activity that captures and prognosticates disease worsening in RRMS. sNfL might therefore be instrumental for a patient-tailored treatment adaptation. We aim to assess whether 6-monthly sNfL monitoring in addition to usual care improves patient-relevant outcomes compared to usual care alone.

Pragmatic multicenter, 1:1 randomized, platform trial embedded in the Swiss Multiple Sclerosis Cohort (SMSC). All patients with RRMS in the SMSC for ≥ 1 year are eligible. We plan to include 915 patients with RRMS, randomly allocated to two groups with different care strategies, one of them new (group A) and one of them usual care (group B). In group A, 6-monthly monitoring of sNfL will together with information on relapses, disability, and magnetic resonance imaging (MRI) inform personalized treatment decisions (e.g., escalation or de-escalation) supported by pre-specified algorithms. In group B, patients will receive usual care with their usual 6- or 12-monthly visits. Two primary outcomes will be used: (1) evidence of disease activity (EDA3: occurrence of relapses, disability worsening, or MRI activity) and (2) quality of life (MQoL-54) using 24-month follow-up. The new treatment strategy with sNfL will be considered superior to usual care if either more patients have no EDA3, or their health-related quality of life increases. Data collection will be embedded within the SMSC using established trial-level quality procedures.

MultiSCRIPT aims to be a platform where research and care are optimally combined to generate evidence to inform personalized decision-making in usual care. This approach aims to foster better personalized treatment and care strategies, at low cost and with rapid translation to clinical practice.

ClinicalTrials.gov NCT06095271. Registered on October 23, 2023.

Amid recent approvals, early Alzheimer's disease (AD) remains an active area of treatment development.

We performed a conjoint experiment to compare preferences among 26 patients with mild cognitive impairment for four trial features including designs incorporating active aducanumab-control (vs. placebo), returning tau positron emission tomography (PET) results (vs. no disclosure), remote study partner participation (vs. in person), and increased risk of brain swelling (vs. lower risk). We used a generalized estimating equation to model the utility of factor levels.

Returning tau PET results had the highest utility (est: 0.47; 95% confidence interval [CI]: 0.13, 0.81; P = 0.007); remote study partner participation showed a similar trend (est: 0.29; 95% CI: -0.05, 0.63; P = 0.097). Trials with active-controlled design (est: 0.01; 95% CI: -0.33, 0.35; P = 0.956) did not demonstrate utility and higher risk of brain swelling had negative utility (est: -0.64; 95% CI: -0.99, -0.30; P < 0.001).

Returning additional biomarker results may increase willingness to enroll in early AD trials.

We compared mild cognitive impairment participant preferences for four trial design features. Returning tau positron emission tomography results had the highest utility. Remote study partner participation showed a positive, albeit non-significant, trend. No utility was observed for an active aducanumab-control design.

Despite a growing body of literature in the area of recruitment modeling for multicenter studies, in practice, statistical models to predict enrollments are rarely used and when they are, they often rely on unrealistic assumptions. The time-dependent Poisson-Gamma model (tPG) is a recently developed flexible methodology which allows analysts to predict recruitments in an ongoing multicenter trial, and its performance has been validated on data from a cohort study. In this article, we illustrate and further validate the tPG model on recruitment data from randomized controlled trials. Additionally, in the appendix, we provide a practical and easy to follow guide to its implementation via the tPG R package. To validate the model, we show the predictive performance of the proposed methodology in forecasting the recruitment process of two HIV vaccine trials conducted by the HIV Vaccine Trials Network in multiple Sub-Saharan countries.

Participant recruitment is one of the most challenging aspects of a clinical trial, directly impacting both the study's duration and the quality of its results. Therefore, reporting successful recruitment strategies is crucial. This study aimed to document the recruitment tactics and experiences of a research team during a university-based randomized clinical trial, conducted as part of a clinical research immersion program. Recruitment took place from October 2021 to October 2022. Before the study commenced, study team members received formal training in clinical trial participant recruitment from the Principal Investigator. The recruitment strategies were integrated into initial study design, which was approved by the Institutional Review Board. A multimodal approach was employed, incorporating both direct and indirect recruitment methods. These strategies successfully met the enrollment target within the twelve-month period. Throughout the process, team members acquired valuable knowledge in recruitment design and implementation, along with transferable interpersonal and networking skills. In-person recruitment was the most efficient and cost-effective strategy, followed by personal referrals. The primary challenge was accommodating participants' availability. Other study teams should consider these recruitment strategies during their study designs. Additionally, the knowledge and skills gained by this study team underscore the value of experiential learning in research education.

This is one of the first reports to summarize the enrollment metrics for ophthalmology trials completed in the United States (US).

This study aimed to describe US ophthalmology clinical trial enrollment metrics to facilitate planning and budgeting of US Food and Drug Administration-regulated ophthalmological drugs trials.

A GlobalData PLC search was conducted on or before February 27, 2024, to evaluate the clinical trial landscape for completed ophthalmology clinical trials conducted in the US. The primary search contained only the term "ophthalmology," which was restricted to trials that were completed and were conducted within the US. Trials were classified as multicenter when trials included three sites or more, and when the enrollment search resulted in ≥30 multicenter trials for an individual indication, enrollment data were further broken down by Food and Drug Administration trial phase.

The search yielded 2229 trials, which analyzed 980 different drugs produced by 854 different sponsors. The most common indications evaluated in US trials were macular degeneration, glaucoma, macular edema, allergies, and keratoconjunctivitis. Multicenter trials by indication had an overall median enrollment period range of 4.8 to 35.1 months; number of subjects enrollment, range of 36 to 518 subjects; number of sites utilized, range of 4 to 74 sites; and enrollment rate, range of 0.11 to 4.04 subjects/sites per month. There were 17 indications with ≥30 multicenter trials, which allowed for enrollment metric calculation by trial phase.

This study provides sponsors with an understanding of the number of subjects and sites needed to complete a trial while also setting realistic enrollment timelines. Although this work represents the US market, more work is needed to better understand other countries given that country-specific guidelines and subject beliefs may impact enrollment metrics.

Anlotinib is an antiangiogenic drug that shows good efficacy and safety in patients with advanced non-small-cell lung cancer (NSCLC). This study aimed to explore the efficacy and safety of anlotinib for consolidation therapy in patients with stage III locally advanced, unresectable NSCLC after concurrent chemoradiotherapy (cCRT). This was a randomized, parallel-controlled, open-label, multicenter, phase II trial of patients with unresectable/nonoperated NSCLC treated with cCRT. The participants were randomized 2:1 to the anlotinib or control group. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the disease control rate (DCR) and overall survival. This study was terminated early due to poor recruitment. Nine and two participants were randomly assigned to the anlotinib and control groups, respectively. One participant in the control group was excluded due to taking prohibited medications before the first efficacy evaluation. In the anlotinib group, the median age was 63 (range, 37-74) years. Two participants achieved partial response, six stable disease, and one progressive disease as best response. The DCR was 88.9%. The median PFS was 11.5 months, and the 12-month PFS rate was 33.9%. All related adverse events were grade 1 or 2. Two participants had a dose adjustment during the study. The evaluable data suggest that anlotinib alone was effective and tolerable in consolidation therapy after cCRT in patients with stage III unresectable NSCLC. The results need to be confirmed by a large-sample trial. This clinical trial was registered on www.clinicaltrials.gov (NCT03743129). Registration date: 6 September 2018.

Although randomised controlled trials (RCT) are considered the optimal form of evidence, there are relatively few in surgery. Surgical RCT are particularly likely to be discontinued with poor recruitment cited as a leading reason. Surgical RCT present challenges over and above those seen in drug trials as the treatment under study may vary between procedures, between surgeons in one unit, and between units in multi-centred RCT. The most contentious and debated area of vascular access remains the role of arteriovenous grafts, and thus the quality of the data that is used to support opinions, guidelines and recommendations is critical. The aim of this review was to determine the extent of variation in the planning and recruitment in all RCT involving AVG. The findings of this are stark: there have been only 31 RCT performed in 31 years, the vast majority of which exhibited major limitations severe enough to undermine the results. This underlines the need for better quality RCT and data, and further inform the design of future studies. Perhaps most fundamental is the planning for a RCT that accounts for the intended population, the uptake of a RCT and the attrition for the significant co-morbidity in this population.

Habitual physical activity (PA) and exercise form a cornerstone of the management of cystic fibrosis (CF), a genetically inherited pulmonary and digestive condition - whereby telehealth platforms have been proposed as a mechanism to engage remotely people with CF in PA and exercise.

To test this, in early 2020, the 'ActivOnline: Physical Activity in Cystic Fibrosis Trial' (ActiOn PACT) randomised control trial was established to examine whether an online intervention was effective at increasing PA in adolescents and adults with CF.

The emergence of the COVID-19 pandemic in 2020 forced this trial to be paused and modified, with the adoption of online recruitment and remote assessment of outcome measures. Despite such adaptations in accord with frameworks developed by the National Institute for Health Research, this trial failed to recruit and was subsequently terminated.

This article details the authors reflections upon the proposed reasons for lack of recruitment, including improved technology and medications for people with CF, and contextualises this finding in relation to the wider issue of non-reporting of trial results in clinical research.