Assessment of Impact of Patient Recruitment Volume on Risk Profile, Outcomes, and Treatment Effect in a Randomized Trial of Ticagrelor Versus Prasugrel in Acute Coronary Syndromes

BACKGROUND Whether there are differences in the risk profile and treatment effect in patients recruited in a low recruitment center (LRC) versus patients recruited in a high recruitment center (HRC) in a randomized multicenter trial remains unknown. METHODS AND RESULTS This study included 4018 patients with acute coronary syndrome recruited in the ISAR‐REACT 5 (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5) trial. The primary end point was a composite of all‐cause death, myocardial infarction, or stroke. Overall, 3011 patients (75%) were recruited in the HRCs (7 centers recruiting 258 to 628 patients; median, 413 patients) and 1007 patients (25%) were recruited in the LRCs (16 centers recruiting 5 to 201 patients; median, 52 patients). Patients recruited in the LRCs had more favorable cardiovascular risk profiles than patients recruited in the HRCs. The primary end point occurred in 72 patients in the LRCs and 249 patients in the HRCs (cumulative incidence, 7.3% and 8.4%; P =0.267). All‐cause mortality was lower among patients recruited in the LRCs (n=29) than among patients recruited in the HRCs (n=134; cumulative incidence 2.9% versus 4.5%; P =0.031). There was no significant interaction between the treatment effect of ticagrelor versus prasugrel and patient recruitment category (LRC versus HRC) regarding the primary efficacy end point (LRC: hazard ratio [HR], 1.42 [95% CI, 0.89–2.28]; HRC: HR, 1.33 [95% CI, 1.04−1.72]; P for interaction=0.800). CONCLUSIONS Patients with acute coronary syndrome recruited in a LRC appear to have more favorable cardiovascular risk profiles and lower 1‐year mortality rates compared with patients recruited in a HRC. The recruitment volume did not interact with the treatment effect of ticagrelor versus prasugrel. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01944800.

113 Simplifying consent - Use of the novel integrated consent model in paediatric clinical research

Primary Subject area Hospital Paediatrics Background Obtaining informed consent from patients to participate in clinical research has traditionally been a cumbersome process, often requiring lengthy documentation and the involvement of trained research staff. Moreover, this process can be a burden to the patient/family. As a result, progress in paediatric research and enabling continual improvement in care has been slow. In the last decade, research ethicists have proposed a new “integrated consent model” (ICM) for obtaining informed consent for pragmatic clinical trials that compare standard-of-care interventions, where there is clinical equipoise. In most cases of ICM, only a brief discussion with verbal consent is required, along with a handout on study purpose, risks, benefits, and procedures. This allows for a more condensed consent process, which maximizes clarity and minimizes information overload. ICM also allows the patient/family to maintain prospective autonomy and decision-making, as compared with deferred or waived consent. The ICM model allows staff in the circle of care to obtain consent, which minimizes the stress of meeting an additional person. To our knowledge, ICM has not yet been used in the paediatric population. Objectives The objective of this abstract is to report on the utility of ICM in a non-randomized clinical trial carried out in the inpatient setting of a tertiary children’s hospital. Design/Methods We compared two widely accepted standards of care for maintaining peripheral intravenous catheter patency in a cohort of children, namely continuous infusion (“to keep the vein open” or TKVO) versus saline lock (SL). The ICM process was reviewed and approved by REB. Nurses in the circle of care received a study package that included an REB approved “consent script” to be read to the patient/family, a single page information sheet, and instructions on documenting the obtained verbal consent in the patient’s chart (Graphic 1). Results With ICM, 79% of participants were recruited into the trial by a nurse. Patient recruitment was completed 4 months ahead of the predicted schedule (Figure 1). Nursing, research, and medical staff were satisfied with ICM and found it easy to administer. ICM occurred smoothly and quickly for patients/families, with no interference with their medical care and practically no disruption to their daily schedule. Conclusion ICM is a practical alternative to laborious traditional consent models, is associated with higher patient recruitment rates, and is less burdensome for the patient/family. Paediatricians should be aware of the utility of this novel consent model.

Does Surgeon Training Affect Patient Perception of Surgeon Skill in DIEP Flap Breast Reconstruction?

Background The aim of this study is to investigate whether a surgeon's training background and years of experience advertised on a social media platform influences perception of surgeon competence, patient recruitment likelihood, and referral likelihood. Methods A mockup of an Instagram post was created using a before and after picture of a deep inferior epigastric perforator (DIEP) flap patient. The caption under each post was changed to reflect one of six possible training categories: 1 year of experience, 10 years of experience, 20 years of experience, fellowship, Ivy League training, and a null case (with no training information against which all other cases were compared). Surveys asked female responders to evaluate surgeon competence, likelihood of becoming a patient, and likelihood of making a referral to their friends or family. Amazon MTurk crowdsourcing platform was used to distribute the survey. Results A total of 1,878 responses were recorded, with the majority identifying as Caucasian (59%). The surgeon with 20 years of experience had the highest patient recruitment scores when compared with the null, 1 year, 10 year, and Ivy League training backgrounds (p = 0.0314, p = 0.0065, p = 0.0207, and p = 0.0244, respectively). The majority of responders (67%) preferred a female surgeon. Responders with a history of breast reconstruction assigned lower surgeon competence scores compared with women without a history of breast cancer (p <0.0001). Women who underwent breast reconstruction were also less likely to make referrals to their family and friends (p <0.0001). Conclusion Surgeon's experience influences whether a patient is likely to seek care from a plastic surgeon. Personal history of breast cancer has a negative impact on perceived surgeon competence as well as patient recruitment likelihood and referral likelihood. Emphasizing fewer years of training or Ivy League training did not make an appreciable difference in patient perception of competence or likelihood of recruiting a new patient.

EP12 Using electronic patient record (EPR) routine data to inform decisions about which ambulance stations should participate in randomised controlled trials

BackgroundTimely recruitment of patients to randomised controlled trials (RCTs) is vital to delivering high-quality, cost-effective research, but RCTs often fail to meet recruitment targets, or meet them more slowly than planned. Ambulance services using electronic patient records (EPR) may be able to use this data to better inform decisions about which sites should participate in future RCTs.MethodsWe used off-the-shelf business intelligence software to examine electronic patient records for all emergency and urgent cases within one English ambulance service for the 287 days 1st January 2020 to 13th October 2020. We adapted inclusion criteria from an upcoming RCT and applied it to this dataset: patient age; trauma mechanism; IV morphine administered. These potentially eligible cases were then displayed by ambulance station, an approximate daily rate per station calculated, and this rate applied to the RCT recruitment period of 304 days. This gave a potentially eligible patient population per station. Finally, we applied a patient conversion rate of 20% to estimate how many participants would be recruited from each station, basing this on recent experience of recruitment to another RCT. The RCT target is 111 patients per station.Results783186 records were reviewed, with 7667 of them potentially eligible for the study. When applied to the proposed study period, there is a potential population of 8121 across the 14 stations. Estimated recruitment per station varied (median 100, range 60-209) and with a 20% conversion rate, 9/14 stations would under-recruit.ConclusionsUsing retrospective data from electronic patient records could be a simple, low-cost way to optimise patient recruitment. Other study criteria could be applied easily, as well as differing conversion rates. We identified ambulance stations where patient recruitment would not be likely to reach study targets, helping inform our decisions around stations as potential study settings.

Why are feasibility studies accessing routinely collected health data? A systematic review

Background: Feasibility trials are often undertaken to determine whether a larger randomised controlled trial (RCT) is achievable. In a recent review, 15 feasibility trials accessed routinely collected health data (RCHD) from UK national databases and registries. This paper looks at attributes of these trials and the reasons why they accessed RCHD. Methods: We extracted data from all publicly available sources for the 15 feasibility studies found in a previous review of trials successfully accessing RCHD in the UK between 2013–2018 for the purpose of informing or supplementing participant data. We extracted trial characteristics, the registry accessed, and the way the RCHD was used. Results: The 15 feasibility RCTs were conducted in a variety of disease areas, and were generally small (median sample size 100, range 41–4061) and individually randomised (60%, 9/15). The primary trial outcome was predominantly administrative (non-clinical) (80%, 12/15) such as feasibility of patient recruitment. They were more likely to recruit from secondary care (67%, 10/15) settings than primary (33%, 5/15). NHS Digital was the most commonly accessed registry (33% (5/15)) with SAIL databank (20% (3/15)), electronic Data Research and Innovation Service (eDRIS) and Paediatric Intensive Care Audit Network (PICANET) (each 13% 2/15) also being accessed. Where the information was clear, the trials used RCHD for data collection during the trial (47%, 7/15), follow-up after the trial (27%, 4/15) and recruitment (13%, 2/15). Conclusions: Between 2013 and 2018, 15 feasibility trials successfully accessed UK RCHD. Feasibility trials would benefit, as with other trials, from guidance on reporting the use of RCHD in protocols and publications.

Are professional pharmacy services being offered for free in pharmacies? A feasibility study exploring the use of a time motion study in New Zealand

Background: Pharmacists report to be providing patient-focused clinical services for which they receive no remuneration. Limited literature exists about unfunded services leading to difficulties in ascertaining an appropriate study design for such research. Objective: This study aims to assess the appropriateness of a proposed study design before launching a nationwide study to investigate the provision of unfunded patient care services. Methods: A multi-methods approach was utilised consisting of (1) continuous time motion study in community pharmacies (2) semi structured patient interviews (3) patient follow up (4) semi structured interviews with pharmacy owners/managers. All observations of unfunded patient care services were recorded, numerically coded and descriptively analysed. Semi structured interviews were audio recorded and transcribed verbatim. A semantic thematic analysis was carried out. Appropriateness of study design was dictated by the ability to characterise services and obtain patient perceptions. Results: Ten pharmacies took part in the feasibility study, across the city of Dunedin, New Zealand, representing a range of different practice settings and demographics. Ten patients were interviewed and six responded to follow up. Both pharmacy and patient recruitment proved challenging due to concerns around disruption to workflow and patient privacy. A continuous observation time motion study was found to be appropriate as it minimises disruption to workflow with no additional work required from the pharmacy teams. Conclusions: A continuous observation time motion study proved to be an appropriate method to investigate the provision of unfunded services on a national scale. The findings of the study suggest design changes such as length of observation time, increasing patient recruitment and additional patient questions to enhance the nationwide study.

Consequences of the COVID-19 Outbreak Lockdown on Non-Viral Infectious Agents as Reported by a Laboratory-Based Surveillance System at the IHU Méditerranée Infection, Marseille, France

The objective of this paper is to describe the surveillance system MIDaS and to show how this system has been used for evaluating the consequences of the French COVID-19 lockdown on the bacterial mix of AP-HM and the antibiotic resistance. MIDas is a kind of surveillance activity hub, allowing the automatic construction of surveillance control boards. We investigated the diversity and resistance of bacterial agents from respiratory, blood, and urine samples during the lockdown period (from week 12 to 35 of 2020), using the same period of years from 2017 to 2019 as control. Taking into account the drop in patient recruitment, several species have exhibited significant changes in their relative abundance (either increasing or decreasing) with changes up to 9%. The changes were more important for respiratory and urine samples than for blood samples. The relative abundance in respiratory samples for the whole studied period was higher during the lockdown. A significant increase in the percentage of wild phenotypes during the lockdown was observed for several species. The use of the MIDaS syndromic collection and surveillance system made it possible to efficiently detect, analyze, and follow changes of the microbiological population as during the lockdown period.

Using Theoretical Domains Framework (TDF) to understand implementation of a pragmatic clinical trial in Public Dental Service in Norway

Background Most dental research in Norway has traditionally been conducted by universities, and the involvement of clinicians in research projects has not been a common practice. The aim of the present study was to identify behavioral factors that influence effective implementation of a pragmatic clinical trial in the Public Dental Service (PDS) in Norway and to understand which of these factors result in higher patient recruitment. Methods Dentists, dental hygienists, and dental assistants at nine Public Dental Service clinics in three counties in Norway involved in an ongoing pragmatic clinical trial were asked to complete an electronically distributed questionnaire based on the Theoretical Domains Framework (TDF). Results Thirty-seven out of 69 dentists and dental hygienists (54 %) and seventeen out of 57 dental assistants (30 %) answered the questionnaire. “Knowledge” was the domain with the highest mean response, suggesting strong confidence in personal knowledge and practical skills among the clinicians. Together with “beliefs about consequences,” “organizational resources,” and “environmental context,” “knowledge” was the one of five domains identified as important behavioral determinants in patient recruitment to clinical trials by dental professionals. Conclusions The findings suggest that TDF was useful to understand factors affecting implementation of clinical trials in PDS and that several factors such as clinical relevance of trial to be implemented, organizational resources, and communication with the research team require more attention when planning and implementing clinical trials in PDS.

Therapy Prospects for Mitochondrial DNA Maintenance Disorders

Mitochondrial DNA depletion and multiple deletions syndromes (MDDS) constitute a group of mitochondrial diseases defined by dysfunctional mitochondrial DNA (mtDNA) replication and maintenance. As is the case for many other mitochondrial diseases, the options for the treatment of these disorders are rather limited today. Some aggressive treatments such as liver transplantation or allogeneic stem cell transplantation are among the few available options for patients with some forms of MDDS. However, in recent years, significant advances in our knowledge of the biochemical pathomechanisms accounting for dysfunctional mtDNA replication have been achieved, which has opened new prospects for the treatment of these often fatal diseases. Current strategies under investigation to treat MDDS range from small molecule substrate enhancement approaches to more complex treatments, such as lentiviral or adenoassociated vector-mediated gene therapy. Some of these experimental therapies have already reached the clinical phase with very promising results, however, they are hampered by the fact that these are all rare disorders and so the patient recruitment potential for clinical trials is very limited.