Randomized Controlled Trials Participants Research Articles

Abstract P3-14-02: A cohort study to evaluate the efficacy and safety of postoperative adjuvant therapy in HER2-positive elderly breast cancer patients (RESPECT-cohort study)

Abstract Background: The randomized controlled trial (RCT) is accepted as the standard clinical trial to decide a standard therapy, but it remains unclear whether or not elderly patients benefit as much as other patients from participation in an RCT. In the RESPECT study (NCT01104935), the relative value of trastuzumab (H) monotherapy as an adjuvant treatment was compared in an RCT with the standard combination treatment with chemotherapy (H+CT) in patients over 70 years old with HER2-positive invasive breast cancer (BC) who received curative surgery. This cohort study was aimed at comparing prognoses between RCT participants (RCT group) and non-participants (Cohort group). Methods: Patients were divided into RCT participants, and those who did not agree to participate in the RCT despite meeting the eligibility criteria and receiving the explanation given by the investigator. In the RCT group patients were randomized to H or H+CT; in the Cohort group treatment was selected for each patient based on the discretion of the treating physician and the patient's wishes without intervention. Treatment categories were divided into three groups: (1) trastuzumab monotherapy group (cH group), (2) trastuzumab plus chemotherapy group (cH+CT group), and (3) those who received either no therapy at all, or any other anticancer therapies without H (cOther group). The primary endpoint was disease-free survival (DFS). Secondary endpoints were overall survival (OS), relapse-free survival, safety, health-related quality of life (HRQOL) and comprehensive geriatric assessment. Results: A total of 275 patients in the RCT group and 123 patients in the Cohort group, in total 398 patients, were enrolled in this study between October 2009 and October 2014. The median age was 74.0 years in the RCT group, 74.5 years in the Cohort group and the median follow-up time was 4.1 years and 3.2 years, respectively. Patients were classified as Stage I: 41.8%, 42.5%; IIA: 41.5 %, 40.8%; IIB: 13.5%, 13.3%; and IIIA: 1.5%. 3.3%, respectively (P = 0.51), there were no significant differences between the two groups. Treatment categories in the Cohort group were: (1) cH group; 43% (n = 52), (2) cH+CT group; 30% (n = 36), cOther group; 27% (n = 32). The planned analysis showed that DFS at 3 years was 91.4% in the RCT group vs 89.3% in the Cohort group (adjusted hazard ratio (HR) = 1.30; 95%CI, 0.72-2.35, P = 0.38). In patients in the cH+CT, cH and cOther group, DFS at 3 years was 92.3%, 89.2% and 82.5%, respectively. DFS in patients in the cH+CT and the cH group was significantly better than that of the cOther group (adjusted HR = 3.79; 95%CI = 1.35-10.64, P = 0.01). DFS in the cH group showed a better tendency compared with cOther (adjusted HR = 2.59; 95%CI, 0.87-7.73, P = 0.08). The incidence of grade 3/4 non-hematological adverse events in the RCT group was relatively higher compared with the Cohort group (18.5% vs 10.8 %, P = 0.05). Conclusion: The prognosis did not vary between the RCT and Cohort groups. H-containing regimens are often chosen for elderly patients with HER2-positive breast cancer. The prognosis of patients who received any H-containing regimen, even H monotherapy, was better than those who were not treated with H. Citation Format: Shinichi Baba, Masataka Sawaki, Yukari Uemura, Tsuyoshi Saito, Kokoro Kobayashi, Hiroaki Kawashima, Michiko Tsuneizumi, Noriko Sagawa, Hiroko Bando, Masato Takahashi, Miki Yamaguchi, Tsutomu Takashima, Takahiro Nakayama, Masahiro Kashiwaba, Toshiro Mizuno, Yutaka Yamamoto, Naruto Taira, Hiroji Iwata, Tatsuya Toyama, Koichiro Tsugawa, Yasuo Ohashi, Hirofumi Mukai. A cohort study to evaluate the efficacy and safety of postoperative adjuvant therapy in HER2-positive elderly breast cancer patients (RESPECT-cohort study) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-14-02.

P070 TRENDS AND CHARACTERISTICS OF CLINICAL TRIALS PARTICIPATION IN THE IBD PARTNERS COHORT

Abstract Background and Aims There are currently several recruitment challenges in randomized controlled trials (RCT) for inflammatory bowel disease (IBD) which prolong the drug approval process and affect the generalizability of study results. The purpose of this study is to characterize individuals who participate in IBD RCTs and identify factors which could influence future recruitment strategies. Methods We performed a cross-sectional study within the IBD Partners cohort comparing patients with current or prior participation in an interventional randomized controlled trial (RCT) of a medical therapy for IBD to those without any RCT participation. Bivariate statistics were used to compare RCT participation by IBD subtype and by other demographic and disease characteristics, and predictive modeling was used to identify factors predictive of RCT participation. We calculated the percent of the cohort that participated an in RCT during each calendar year from 2011–2018 and Clinicaltrials.gov was accessed to determine the number of active RCTs for IBD therapies per year during that same period. Results A total of 14,747 patients with IBD were included in the analysis and 1,116 (7.6%) reported RCT participation at any time. Demographic factors predictive of RCT participation (Table 1) included following at an academic institution (OR=1.8; 95%CI: 1.51–2.04) and age 36–75 (OR=1.6; 95%CI: 1.43–1.87). Patients with Crohn’s disease (CD) were more likely to participate than those with ulcerative colitis (UC) (OR=1.5; 95%CI: 1.35–1.77). Patients with more severe disease were more likely to participate, including those with prior IBD-related hospitalization (OR=2.6; 95%CI: 2.19–2.99), IBD-related surgery (OR=2.5; 95%CI: 2.24–2.87), biologic exposure (OR=3.2; 95%CI: 2.76–3.65), and “Poor” or worse quality of life (OR=1.7; 95%CI: 1.45–1.93). Steroid-free remission was associated with lower likelihood of RCT participation (OR=0.6; 95%CI: 0.53–0.70). While the number of active RCTs for IBD more than doubled between 2011 and 2018, RCT participation rates during that same time period decreased from 1.1% to 0.7% of the cohort (Figure 1). Conclusions RCT participation rates declined within this cohort between 2011–2018. Groups underrepresented in RCTs for IBD included younger patients, patients followed in community settings, and patients with more mild disease. The non-RCT group had mean sCDAI and SCCAI scores that did not meet remission thresholds, demonstrating populations in need of alternate therapies for whom clinical trials could be an option. Given anti-TNF exposure rates in this national cohort, studies should focus on anti-TNF failure populations. Investigators should make every effort to offer RCTs to all patients and network with community providers to increase awareness of RCTs.

The research burden of randomized controlled trial participation: a systematic thematic synthesis of qualitative evidence

BackgroundParticipation in randomized controlled trials (RCTs) may be quite demanding and could represent an important burden for patients. We aimed to explore this research burden (i.e., the psychological, physical, and financial burdens) experienced by patients through their participation in a RCT.MethodsWe conducted a systematic review of qualitative studies exploring adult patients’ experiences with RCT participation. We searched MEDLINE (PubMed), CINAHL, PSYCHINFO, and Embase (search date March 2018) for eligible reports. Qualitative data coding and indexing were assisted by NVivo. The quality of reports was assessed by using the Critical Appraisal Skills Program (CASP) tool.ResultsWe included 45 qualitative studies that involved 1732 RCT participants. Important psychological burdens were identified at every stage of the trial process. Participants reported feeling anxiety and being afraid of “being a ‘guinea pig’” and described undergoing randomization and allocation to a placebo as particularly difficult resulting in disappointment, anger, and depression. Patients’ follow-up and trial closure were also responsible for a wide range of psychological, physical, and financial burdens. Furthermore, factors related to burdensome impacts and consequences were discerned. These factors involved trial information, poorly organized and too-demanding follow-up, and lack of appropriate management when the patient’s participation ended. Trial participation was also associated with beneficial effects such as the satisfaction of feeling “useful,” gaining “a sense of control,” and receiving special attention.ConclusionsOur finding provides a detailed description of research burden across the whole RCT process. Many of the burdens described could be anticipated, and some avoided in a movement toward minimally disruptive clinical research. Such an approach could improve trial recruitment and retention.Review registrationPROSPERO CRD42018098994

Interpersonal and Social Rhythm Therapy for Patients With Major Depressive Disorder.

This study aimed to conduct a safety analysis among patients with major depressive disorder receiving interpersonal and social rhythm therapy (IPSRT) with and without cognitive remediation. This preliminary safety analysis of the outcomes of patients with major depressive disorder was part of a larger randomized controlled trial (RCT) in which patients with bipolar disorder and major depressive disorder received IPSRT; half were randomly assigned to receive additional cognitive remediation. The study focused on patients with major depressive disorder because IPSRT had not been trialed with this group; their outcomes were compared with those of patients with bipolar disorder. Data from the first 30 RCT participants were used to examine whether the intervention had adverse effects, whether mood symptoms and functioning improved over 12 months, and whether there was a signal of benefit. Mood symptoms were measured at baseline and 12 months with the Longitudinal Interval Follow-Up Evaluation and the Quick Inventory of Depressive Symptoms-Self-Reported; functioning was measured with the Social Adjustment Scale. A total of 63% (N=19) of participants were diagnosed with bipolar disorder and 27% (N=11) with major depressive disorder. No adverse effects were found for those with major depressive disorder, and improvements were seen in mean depressive and functioning scores at 12 months compared with baseline, with moderate to large effect sizes. IPSRT may be a clinically effective intervention for patients with major depressive disorder. Outcomes related to cognitive functioning and the effects of cognitive remediation will be reported at the end of the trial.

A Mobile Health App to Improve HIV Medication Adherence: Protocol for a Pilot Randomized Controlled Trial.

BackgroundAdherence to antiretroviral therapy (ART) is essential for allowing persons living with HIV to live longer, healthier lives. However, a large portion of this population has suboptimal adherence and are not virally suppressed. Conventional interventions aimed at improving ART adherence lack portability and scalability, and improvements in adherence are not often sustained. Mobile health (mHealth) ART interventions offer a low-cost and accessible method of improving adherence, but many have limited functionality and do not offer comprehensive support. The combination of an mHealth intervention with a face-to-face adherence intervention and interactive health coaching feature may offer sufficient support in a manner that is sensitive to resource limitations that are often found in HIV treatment settings. This paper details the protocol of a study designed to evaluate the potential of an enhanced mHealth intervention for improving ART adherence.ObjectiveThe primary objective of this study is to assess the feasibility and acceptability of the Fitbit Plus app enhanced with a face-to-face LifeSteps session (Fitbit Plus condition) for improving ART adherence. In addition, we will determine the preliminary efficacy of the intervention by calculating treatment effect sizes.MethodsThis study will be conducted in 2 phases. The intervention will be developed and piloted with a small group of participants during phase 1. Pilot participants will provide feedback that will be used to refine the intervention for phase 2. In phase 2, a preliminary randomized controlled trial (RCT) comparing Fitbit Plus with a condition that approximates the standard of care (SOC) will be conducted with 60 persons living with HIV. Interviews will be conducted with RCT participants at baseline, and follow-up interviews will be conducted at 1, 3, 6, and 12 months. ART adherence is the primary outcome and will be monitored throughout the study via electronic pill boxes. Effect sizes will be generated using a fractional logit model estimated by generalized estimating equations.ResultsPhase 1 of this trial is complete; data collection for phase 2 is ongoing. Follow-ups with enrolled participants will conclude in January 2020.ConclusionsThis study will contribute to the literature on ART adherence and may produce an efficacious intervention. Owing to a small sample size, there may be insufficient power to detect statistically significant differences between Fitbit Plus and SOC. However, if Fitbit Plus is found to be acceptable and feasible and yields promising effect size estimates, this pilot study could serve as the foundation for a larger, fully powered trial of Fitbit Plus.Trial RegistrationClinicalTrials.gov NCT02676128; https://clinicaltrials.gov/ct2/show/NCT02676128International Registered Report Identifier (IRRID)DERR1-10.2196/15356

P6410Eligibility and preference of extended antithrombotic therapy for secondary prevention after an acute coronary syndrome

Abstract Background and purpose Recent randomized controlled trials (RCTs) have evaluated the benefit of extended antithrombotic therapy in secondary prevention of Acute Coronary Syndromes (ACS). However, the numerous and strict enrollment criteria may limit the validity and reproducibility of the published results in clinical practice. We aimed to estimate the eligibility for participation in RCTs of a group of patients followed up for ACS. Methods We applied the enrollment criteria of 2 RCTs (PEGASUS [low-dose ticagrelor – 60mg twice daily] and COMPASS [low-dose rivaroxaban – 2.5mg twice daily) to 780patients with history of ACS. Results A total of 938 patients admitted for ACS during 30months. Mean age was 68.8±10.3 years, 70.4% (n=660) males. Baseline characteristics are summarised in Table 1. Median length of stay was 6.0 (IQR 3.0–11.0 days). In-hospital mortality was 7.9%. Mortality after discharge within 12 months was 9.7%. A total of 780 patients were screened for trial enrollment after 12 months of follow-up. The proportion of patients fulfilling the trial enrollment criteria were 32.1% for PEGASUS and 35.9% for COMPASS. 41.6% of patients were eligible for at least one RCT. The main reasons for ineligibility for RCTs were the presence of comorbidities for PEGASUS and bleeding risk for COMPASS (Figure 1). Patients not fulfilling enrollment criteria for any RCT (58.4%) were older (71.4±9.7 vs 65.2±10.2 years, p<0.0001), more likely to have worse renal function (CrCl 47.8±28.8 vs 73.9±21.2 ml/min/1.73m2, p<0.0001), less left ventricular ejection fraction (44.4±11.4 vs 51.9±7.5%, p<0.0001) and had longer length of stay (7 IQR 4–13 vs 5 IQR 3–8 days, p<0.0001). The main differences in eligible and ineligible patients in both RCTs are summarised in Table 2. Baseline characteristics and differences Conclusions Patients enrolled in RCTs are only partly representative of the real world population with history of ACS, mainly due to the higher prevalence of comorbidities and bleeding risk factors in this population. It is uncertain if these patients still benefit from theses therapies as in the published RCTs.

Learning Personalized Treatment Rules from Electronic Health Records Using Topic Modeling Feature Extraction.

To address substantial heterogeneity in patient response to treatment of chronic disorders and achieve the promise of precision medicine, individualized treatment rules (ITRs) are estimated to tailor treatments according to patient-specific characteristics. Randomized controlled trials (RCTs) provide gold standard data for learning ITRs not subject to confounding bias. However, RCTs are often conducted under stringent inclusion/exclusion criteria, and participants in RCTs may not reflect the general patient population. Thus, ITRs learned from RCTs lack generalizability to the broader real world patient population. Real world databases such as electronic health records (EHRs) provide new resources as complements to RCTs to facilitate evidence-based research for personalized medicine. However, to ensure the validity of ITRs learned from EHRs, a number of challenges including confounding bias and selection bias must be addressed. In this work, we propose a matching-based machine learning method to estimate optimal individualized treatment rules from EHRs using interpretable features extracted from EHR documentation of medications and ICD diagnoses codes. We use a latent Dirichlet allocation (LDA) model to extract latent topics and weights as features for learning ITRs. Our method achieves confounding reduction in observational studies through matching treated and untreated individuals and improves treatment optimization by augmenting feature space with clinically meaningful LDA-based features. We apply the method to EHR data collected at New York Presbyterian Hospital clinical data warehouse in studying optimal second-line treatment for type 2 diabetes (T2D) patients. We use cross validation to show that ITRs outperforms uniform treatment strategies (i.e., assigning same treatment to all individuals), and including topic modeling features leads to more reduction of post-treatment complications.

TRUST Study: Participation in Randomized Controlled Trials and Subsequent Adherence to Visiting Medical Institutions and Taking Medications in Patients with Cardiovascular Diseases. Part I. Motives for the Patients' Participation in Clinical Trials

Aim. To describe the design of TRUST study (Influence of Participation in Randomized Controlled Trials on adheRence to Medicines' Intake and regUlar viSits to the docTor) and present the first part of this study to determine the motives of patient participation in clinical trials.Material and methods. The main group of TRUST study included patients of the outpatient registrar PROFILE, which were taking part in one or more international randomized clinical trials, conducted from 2011 to 2018. The standard registration card of PROFILE register was used to assess the clinical and demographic data of patients.In 2019 full-time/telephone contact with patients was established, during which, based on the original questionnaire, the motives of the participation in trials, their attitude towards randomized controlled trials (RCT), and their adherence to monitoring in medical institutions were determined. This publication presents the results of the first part of the study.Results. 102 patients were enrolled in the study, telephone /personal contact was established for 88 patients, the life status of 9 of them by 2019 was defined as "dead", 77 were interviewed, 2 – refused to answer. Over 80% of patients completed participation in RCTs more than one year ago. 71.6% of patients participated in more than one RCT. In 60% of cases, patients claimed that this was the proposal of the doctor of the scientific center. For 79% of patients, RCTs had the opportunity to access highly skilled medical care. Only 18% of patients indicated that they received the necessary qualified medical care before entering the study. In cases where patients answered dichotomous questions (such as "yes"/"no"), the overwhelming majority of patients (74%) claimed that it was the authority of the doctor of the scientific center and the fear of losing the possibility of further observation became the main reason for participating in RCTs.Conclusion. In the first part of the TRUST study, it was revealed that in Russia the main reason of participation in RCT is the recommendation of a doctor from a specialized scientific center.

SAT-041 A META-ANALYSIS OF THE REPRESENTATIVENESS OF RANDOMIZED CONTROLLED TRIAL COHORTS IN END-STAGE KIDNEY DISEASE

Systematic differences between patients included in randomized controlled trials (RCTs) and the general patient population may influence the generalizability of RCT findings. Comprehensive national registries of patients with end-stage kidney disease (ESKD) on dialysis provide a unique opportunity to compare trial and real-world patient cohorts. We aimed to determine if participants in large, multicentre dialysis trials were similar to the general dialysis population in terms of age, co-morbidities and mortality rate. Medline, PubMed and the Cochrane Central Register of Controlled Trials were systematically searched from 2007 to 2016. Data sources were published manuscripts, supplementary material and trial registration information. General dialysis population data was derived from US Renal Data System (USRDS). RCTs enrolling only participants on dialysis for ESKD; with ≥100 adult participants from ≥2 sites were included. Abstract screening and data extraction were performed independently by two researchers. Data were pooled using a random-effects model. The primary outcome was difference in mean age between the RCT and USRDS populations. Secondary outcomes included differences in mortality rate and co-morbidities. We identified 189 RCTs, enrolling 80,104 participants. Compared to the 2011 USRDS population, RCT participants were younger (58.9 [95% confidence interval 58.3-59.5] vs 61.2 years; P<0.001), more likely to be male (58.8% [57.5-60.0] vs 55.7%; P<0.001) and to have coronary artery disease (26.7% [22.1-31.4] vs 17.7%; P<0.001) and less likely to have diabetes (40.4% [36.9-43.8] vs 44.2%; P=0.035) or heart failure (19.9 [15.6-24.3] vs 29.8; P<0.001). The mortality rate during trial participation was less than half that of the USRDS population (8.92 [7.85-10.00] vs 18.59 per 100 patient-years; P<0.001). The differences in age, mortality and coronary artery disease remained when studies recruiting only from the USA were considered. Diabetes was more common in RCT participants from the USA than in the registry population. Participants in large, multicentre dialysis RCTs are younger, have a different pattern of co-morbidities and a lower mortality rate than the general dialysis population. This finding has implications for the generalization of trial results to the broader patient population and for future trial design.

A novel group parenting intervention to reduce emotional and behavioural difficulties in young autistic children: protocol for the Autism Spectrum Treatment and Resilience pilot randomised controlled trial

IntroductionThe majority of young autistic children display impairing emotional and behavioural difficulties that contribute to family stress. There is some evidence that behavioural parenting interventions are effective for reducing behavioural...

Exploring compassionate attributes and skills among individuals participating in compassion-focused therapy for enhancing well-being.

ObjectivesThe conceptual approach of compassion underlying compassion‐focused therapy (CFT) is based on theoretical rather than empirical grounds. The aim of the present study was to seek empirical support for components of compassion as outlined in the theoretical model underpinning CFT, and to explore which components, if any, matter most for improving well‐being.DesignA sequential exploratory mixed methods design was employed.MethodsAlongside a randomized controlled trial (RCT), we systematically examined 625 emails sent by 87 RCT participants to five counsellors during the course of a well‐being enhancing CFT self‐help intervention, to identify theoretically based compassionate attributes and skills. Next, in a quantitative analysis, we compared participants who did and did not show clinically relevant improvement on well‐being with regard to the occurrence of compassionate attributes and skills.ResultsAlthough the theoretical model of compassion integral to CFT was largely supported by the emails, it was slightly simplified so as to better fit the data. The adjusted model comprises five compassionate attributes (i.e., care for well‐being, sensitivity, empathy, distress tolerance, and common humanity) and four compassionate skills (i.e., compassionate attention, reasoning, behaviour, and feeling/sensation). Three illustrative cases are presented to contribute to a better understanding of fundamental components of compassion. Quantitative analyses indicate that participants showing clinically relevant improvement on well‐being expressed significantly more compassionate feeling/sensation compared to those who did not.ConclusionsWe found preliminary evidence for the conceptualization of compassion underlying CFT. Compassionate feeling/sensation bears particular interest when well‐being is the intended outcome of CFT.Practitioner points Individuals participating in compassion‐focused therapy for enhancing well‐being experience a wide range of compassionate attributes and skills.Compassion‐focused therapy may instigate well‐being if a client is able to experience compassionate feeling/sensation.

Evidence of heterogeneity in statin-associated type 2 diabetes mellitus risk: A meta-analysis of randomized controlled trials and observational studies

AimsTo conduct a meta-analysis of statin-associated type 2 diabetes mellitus (T2D) risk among randomized controlled trials (RCTs) and observational studies (OBSs), excluding studies conducted among secondary prevention populations. MethodsStudies were identified by searching PubMed (1994-present) and EMBASE (1994-present). Articles had to meet the following criteria: (1) follow-up >one year; (2) >50% of participants free of clinically diagnosed ASCVD; (3) adult participants ≥30 years old; (4) reported statin-associated T2D effect estimates; and (5) quantified precision using 95% confidence interval. Data were pooled using random-effects model. ResultsWe identified 23 studies (35% RCTs) of n = 4,012,555 participants. OBS participants were on average younger (mean difference = 6.2 years) and had lower mean low-density lipoprotein cholesterol (LDL-C, mean difference = 20.6 mg/dL) and mean fasting plasma glucose (mean difference = 5.2 mg/dL) compared to RCT participants. There was little evidence for publication bias (P > 0.1). However, evidence of heterogeneity was observed overall and among OBSs and RCTs (PCochran = <0.05). OBS designs, younger baseline mean ages, lower LDL-C concentrations, and high proportions of never or former smokers were significantly associated with increased statin-associated T2D risk. ConclusionsPotentially elevated statin-associated T2D risk in younger populations with lower LDL-C merits further investigation in light of evolving statin guidelines targeting primary prevention populations.

Linezolid for drug-resistant pulmonary tuberculosis.

Linezolid for drug-resistant pulmonary tuberculosis.

Linking women experiencing incarceration to community-based HIV pre-exposure prophylaxis care: protocol of a pilot trial

BackgroundWomen experiencing incarceration (WEI) engage in high rates of sex- and drug-related behavior that places them at risk for HIV. Pre-exposure prophylaxis (PrEP) is an efficacious means of reducing HIV acquisition. There is a general lack of knowledge regarding PrEP among women at elevated risk, and only a small percentage of at-risk women are currently engaged in PrEP care. The period of incarceration represents an opportunity to identify at-risk women, initiate PrEP during incarceration, and establish linkage to community-based PrEP care upon release from incarceration. Further, post-release is a time period that is particularly risky, and there are numerous barriers, including substance use, that may impede linkage to community-based care in the absence of intervention. The current protocol describes plans for the development and pilot randomized controlled trial (RCT) of an intervention to promote PrEP uptake during incarceration and facilitate linkage to community-based PrEP care post-release.Methods/designThe motivational interviewing-navigation (MI-NAV) study intervention is being developed, refined, and tested over three phases within the framework of the social ecological model. All phases of the study are being conducted at a women’s correctional facility and community-based PrEP provider located in the Northeastern region of the United States. Phase 1 consists of individual qualitative interviews to be conducted with key stakeholders (n = 6–10) from the community-based PrEP care site and (n = 6–10) from the women’s correctional facility, as well as with (n = 18–30) WEI. Recruitment for Phase 1 was initiated in November 2017. In Phase 2, MI-NAV will be piloted with a small cohort (n = 8–12) of WEI and will be refined based upon participant feedback. During Phase 3, a pilot RCT of MI-NAV and a standard of care condition will be conducted with 80 WEI. RCT participants will complete baseline and follow-up assessments 1, 3, and 6 months post-release. The primary study outcome is linkage to community-based PrEP care, verified via medical records.DiscussionThis study will develop and evaluate a psychosocial intervention (MI-NAV) to promote PrEP uptake and facilitate linkage to community-based PrEP care among women at-risk for HIV. It is expected that, as a result of this project, the feasibility, acceptability, and preliminary efficacy of MI-NAV will be determined. If found to be efficacious, this intervention has the potential to reduce HIV acquisition in a high-need, underserved community.Clinical trial registration NCT03281343

Long-Term Effects of Randomization to a Weight Loss Intervention in Older Adults: A Pilot Study

Randomized, controlled trials (RCTs) show intentional weight loss improves body composition and physical function in older adults; however, the long-term benefits (and risks) are unknown. We conducted a pilot study to assess the feasibility of recalling prior RCT participants to examine the long-term effects of intentional weight loss on body composition and physical function. A weighted, random sample of 60 older adults who were randomized to caloric restriction plus exercise (CR + EX) or exercise (EX) only in 5 prior RCTs (mean age at randomization, 67.3 years; 69% women, 80% white) were invited to participate. Follow-up was obtained on 89% (42 clinic visits, 10 phone interviews, 1 death) an average of 3.5 years (range, 2.2–5.8 years) after RCT completion. Despite greater weight, fat and lean mass loss during the RCT (mean difference in change (95% CI): −4.19 (−7.52, −0.86), −2.75 (−5.10, −0.40), and −2.32 (−3.69, −0.95) kg, respectively) in those randomized to CR + EX, long-term changes in weight (2.05 (−2.35, 6.45) kg) and body composition (1.80 (−1.56, 5.17) and 0.03 (−2.20, 2.26) kg for fat and lean mass, respectively) from baseline and physical function at long-term follow-up (mean difference in 400-m walk and SPPB (95% CI): 23.2 (−19.3, 65.6) sec and −0.03 (−1.02, 0.96) points, respectively) were similar in CR + EX and EX only. Although improvements in weight and body composition following intentional weight loss may not be sustained long-term, physical function does not appear to be negatively impacted. A larger study is needed to confirm these results.

OP88 Digital Approaches For Randomized Controlled Trial Recruitment Or Retention: A Systematic Map

IntroductionRecruitment and retention of participants in randomized controlled trials (RCTs) is challenging, and is why many RCTs fail or are not completed on time. Digital approaches such as social media, data mining, email or text messaging could improve recruitment and/or retention, but how well they match these purposes is unclear. We used systematic methods to map the digital approaches that have been investigated during the past 10 years.MethodsWe searched Medline, Embase, other databases and relevant web sites in July 2018 to identify comparative studies of digital approaches for recruiting and/or retaining participants in clinical or health RCTs. Two reviewers screened references against protocol-specified eligibility criteria. Studies included were coded by one reviewer (with 20 percent checked by a second reviewer) using pre-defined keywords to describe characteristics of the studies, populations and digital approaches evaluated.ResultsWe identified 9,133 potentially relevant references, of which 100, reporting 101 unique studies, met the criteria for inclusion in the map. Among these, 95 percent of studies investigated recruitment but only 11 percent investigated retention. Study areas included health promotion and public health (36 percent), cancer (17 percent), circulatory system disorders (13 percent) and mental health (10 percent). Most study designs were observational (89 percent). The most frequent digital approaches for recruitment were internet sites (53 percent of recruitment studies), social media (42 percent), television or radio (31 percent) and/or email (31 percent). For retention these were email (63 percent of retention studies) or text messaging (38 percent). Time and costs of recruitment were reported in 17 percent and 30 percent of recruitment studies respectively, whilst costs were reported in 19 percent of retention studies.ConclusionsA wide range of digital approaches has been studied, in many combinations. Evidence gaps include lack of experimental studies; studies on retention; and studies for specific populations (e.g. children or older people) and outcomes (e.g. user satisfaction). More robust experimental studies, perhaps conducted as studies-within-a-trial (SWAT), are needed to address knowledge gaps and ensure that estimates of digital tool effectiveness and efficiency are reliable.

Can Watching a Television Documentary Change the Way Men View Masculinity?

Men’s conformity to masculine norms, such as stoicism and self-reliance, has been shown to be associated with a range of negative psychological outcomes. We developed Man Up—a three-part documentary that examined the link between masculinity, mental health, and suicide for men in Australia. We conducted a multifaceted evaluation that included a randomized controlled trial (RCT) and a web survey. RCT participants and web survey respondents were asked how their views of the term “man up” had changed since watching the documentary. This article provides feedback from the 306 men who responded to this question. Participants commented on how the documentary prompted them to rethink stereotypes of masculinity. The findings suggest that the documentary had a positive impact on men.

The Representativeness of Participants With Severe Mental Illness in a Psychosocial Clinical Trial.

Introduction: Cardiovascular morbidity and mortality are increased in severe mental illnesses (SMI). Trials of psychosocial health interventions to improve physical health in SMI, including in treatment-resistant schizophrenia, have shown some benefit. However, the representativeness of participants in such trials has not been determined.Method: We utilized an anonymised case register to determine if participants in a randomized controlled trial (RCT) of a novel psychosocial health intervention aiming to improve physical health in SMI had similar severity of illness to eligible non-participants. A retrospective database analysis was performed, using Health of the Nation Outcome Scale (HoNOS) data from the sample of patients participating in the IMPaCT (Improving Physical health and reducing substance use in Psychosis) RCT (n = 293) compared to all eligible participants with a psychotic illness (n = 774).Results: The mean total HoNOS score in the eligible comparator population (Mean = 9.09, SD = 5.8, range = 0–30) was significantly greater than that of the IMPaCT RCT participants (Mean = 7.16, SD = 4.7, range = 0–26), (t = 3.810, p = 0.006), as was the degree of overall illness severity and functional impairment, as measured by HoNOS.Conclusion: This study shows for the first time that the patient population participating in an RCT of a lifestyle intervention for those with SMI had a better mental health status at entry to the trial, than the total eligible population, although there was no difference in physical health needs. This has relevance to the applicability of RCTs of lifestyle interventions in service planning and suggests that when people are more unwell, greater effort may be needed to include them in psychosocial interventions. A more careful and focused recruitment approach should be followed to improve the participation of the more severely ill patients in psychosocial interventions in order to enhance the external validity of such studies.

Process evaluation of a randomised controlled trial of a pharmacological strategy to improve hypertension control: protocol for a qualitative study

IntroductionGlobally, the prevalence of uncontrolled hypertension is high, particularly in low- and middle-income countries. There is a critical need for strategies to improve hypertension control. The early use of a...

Intermittent Fasting (Alternate Day Fasting) in Healthy, Non-obese Adults: Protocol for a Cohort Trial with an Embedded Randomized Controlled Pilot Trial.

Background/objectivesAlternate day fasting (ADF) is a subtype of intermittent fasting and is defined as a continuous sequence of a fast day (100% energy restriction, zero calories) and a feed day (ad libitum food consumption), resulting in roughly 36-h fasting periods. Previous studies demonstrated weight reductions and improvements of cardiovascular risk factors with ADF in obese subjects. However, rigorous data on potential endocrine, metabolic and cardiovascular effects, besides weight loss, are lacking. Therefore we aim to investigate the short- and mid- to long-term clinical and molecular effects of ADF in healthy non-obese subjects.MethodsWe will perform a prospective cohort study with an embedded randomized controlled trial (RCT) including 90 healthy subjects. Thirty of them will have performed ADF for at least 6 months (mid-term group). Sixty healthy subjects without a particular diet before enrolment will serve as the control group. These subjects will be 1:1 randomized to either continuing their current diet or performing ADF for 4 weeks. All subjects will undergo study procedures that will be repeated in RCT participants after 4 weeks. These procedures will include assessment of outcome parameters, dual-energy X-ray absorptiometry, measurement of endothelial function, an oral glucose tolerance test, 24-h blood pressure measurement, retinal vessel analysis, echocardiography and physical activity measurement by an accelerometer. Blood, sputum, buccal mucosa and faeces will be collected for laboratory analyses. Participants in the RCT will wear a continuous glucose monitor to verify adherence to the study intervention.Planned outcomesThe aim of this project is to investigate the effects of ADF on human physiology and molecular cellular processes. This investigation should gain in-depth mechanistic insights into the concept of ADF and form the basis for larger subsequent cohort recruitment and consecutive intervention studies.Trial registrationNCT02673515; registered 24 November 2015. Current protocol date/version: 7 February 2017/version 1.8.