Clinical Oversight Research Articles

The Mayo Clinic Cellular Therapy Fellowship: Training the Next Generation of Cellular Therapy Leaders

Background & Aim The field of cellular therapy is rapidly evolving with promising clinical outcomes and multiple potential therapeutic targets. This rapid expansion, while exciting, has quickly led to a deficit of qualified directors for burgeoning human cellular therapy laboratories. Unlike conventional drug therapies, cellular based therapies require an added layer of expertise in policy, good manufacturing practices (cGMP) and regulatory elements. Academic medical centers, both nationally and internationally, are in desperate need of well-trained, experienced leaders capable of directing the labs which both oversee and produce these therapeutic agents. To meet this need, we have established the Mayo Clinic School of Graduate Medical Education (MSGME) Cellular Therapy Fellowship; an intensive one-year program for M.D. and Ph.D. candidates consisting of didactic, experiential, and project-driven training with an emphasis on laboratory management and graduated responsibility. Mayo Clinic is a multidisciplinary academic medical and research institution, which houses a lab that directly supports the bone marrow transplant service in addition to a multifaceted immune and progenitor cell program focusing on investigational cell therapies such as mesenchymal stem cells, dendritic cells, and CAR T cells. The program is robust performing more than 500 clinical stem cell transplants annually and encompassing more than 25 active investigator-initiated trials in addition to greater than 30 external manufacturing protocols. Our aim is to produce scientific and clinical leaders fluent in cGMP regulations, quality control and regulatory components, clinical laboratory management, current methodologies in cell therapy manufacturing, IND preparation and clinical trial oversight. Methods, Results & Conclusion Our curriculum mirrors this aim with rotations in the BMT and progenitor cell laboratories, our commercial processing unit, CAR-T manufacturing, quality, apheresis and infusions and leadership and management each with varying levels of graduated responsibility and on-call duties. The fellows actively participate in director level conversations and decisions, which, in combination with the aforementioned experiences and their research projects, provides a thorough and comprehensive training experience for the next generation of cell therapy leaders.

Anti-cancer therapy and clinical trial considerations for gynecologic oncology patients during the COVID-19 pandemic crisis

ObjectivesThe COVID-19 pandemic has consumed considerable resources and has impacted the delivery of cancer care. Patients with cancer may have factors which place them at high risk for COVID 19 morbidity or mortality. Highly immunosuppressive chemotherapy regimens and possible exposure to COVID-19 during treatment may put patients at additional risk. The Society of Gynecologic Oncology convened an expert panel to address recommendations for best practices during this crisis to minimize risk to patients from deviations in cancer care and from COVID-19 morbidity. MethodsAn expert panel convened to develop initial consensus guidelines regarding anti-neoplastic therapy during the COVID-19 pandemic with respect to gynecologic cancer care and clinical trials. ResultsCOVID-19 poses special risks to patients who are older, have medical co-morbidities, and cancer. In addition, this pandemic will likely strain resources, making delivery of cancer care or conduct of clinical trials unpredictable. Recommendations are to limit visits and contact with health care facilities by using telemedicine when appropriate, and choosing regimens which require less frequent visits and which are less immunosuppressive. Deviations will occur in clinical trials as a result of limited resources, and it is important to understand regulatory obligations to trial sponsors as well as to the IRB to ensure that clinical trial and patient safety oversight are maintained. ConclusionsThe ongoing crisis will strain resources needed to deliver cancer care. When alterations to the delivery of care are mandated, efforts should be taken to minimize risks and maximize safety while approximating standard practice.

Ensuring Successful Telepsychiatry Program Implementation: Critical Components and Considerations

Telepsychiatry in the USA witnessed exponential growth in the last decade, having been proven to be a cost-effective and sustainable approach to delivering high-quality mental health services. This surge was aided by the availability of high-speed Internet, improved software, and an increase in demand paired with expanded reimbursement models. Despite a growing interest in adopting telepsychiatry programs, many health organizations continue to face challenges at the implementation stage. This review aims to identify the critical components and the associated challenges met at the planning, deployment, and maintenance phases of telepsychiatry program implementation. Four critical components for telepsychiatry implementation have been identified: (1) patient population, (2) originating site, (3) tele-clinician, (4) the information and communications technologies, and a potential fifth (5) a telepsychiatry organization to help align these components. Recommendations to anticipate and address these challenges include assessing the needs of the patient population, incorporating standardized processes and data analytics into existing organizations workflow, sourcing qualified and culturally competent tele-clinicians and providing ongoing clinical oversight, technological support, and monitoring of connectivity. The rapid growth of telepsychiatry programs in the USA is concomitant with a number of critical implementation challenges. Recommended strategies and applied solutions are discussed in this review.

Predictive factors of facilitating linkage to care for HIV-positive detainees in ICE Health Service Corps-staffed facilities.

Persons in ICE detention represent a population about whom limited health-related data is available in the literature. Since ICE detention is generally brief, facilitating linkage to care (FLC) for detainees with chronic diseases, including HIV-positive detainees, is challenging, yet critical to encourage continued treatment beyond custody. Between 2015 and 2017, IHSC-staffed facilities implemented intensive training related to HIV care and FLC and increased clinical oversight and consultations. This study examined the impact of these changes in relation to FLC. Demographic and clinical data for detainees with known HIV-positive diagnoses at IHSC-staffed facilities entering custody in 2015 and 2017 were obtained via electronic health record. Univariate analysis and multiple logistic regressions were performed to identify factors that may increase FLC. After adjusting for year of entry into custody, detainees who received an infectious disease (ID) consultation had significantly higher odds (2.4, P<0.001) of receiving FLC resources compared to those who did not receive an ID consultation. Between 2015 and 2017, the proportion of HIV-positive detainees receiving FLC resources increased from 29 to 62%. ID consultations significantly improved FLC for HIV-positive detainees. Continued provider training and education is essential to continue improving the rate of FLC for HIV-positive ICE detainees.

Translating the Rapidly Evolving CAR-TCR Research Portfolio to Clinical Practice, a Single Institution Experience at an Academic Medical Center

Topic Significance/Background This is an unparalleled time in cancer research, particularly with the use of cellular therapeutics to target both solid and liquid tumors. This science is challenging the boundaries of clinical care to update guidelines, streamline processes, and integrate clinical and research teams. The University of Kansas Cancer Center was launched into the cell therapy space when we enrolled the first adult patient on Novartis Juliet CAR-T trial for DLBCL. Our team learned that inpatient and outpatient infrastructure and multidisciplinary collaboration are essential to promoting quality clinical care to complement this innovative new field of cellular immunotherapy. As of September 2019, our center has 19 active cell therapy trials, 10 studies in start-up, and 27 in the research pipeline. We have had the opportunity to participate in clinical trials assessing safety and efficacy of TILs, CAR-T and TCR in the cell therapy space, along with expanded umbilical, placental, and mesenchymal stem cell products. In order to optimally contribute in this dynamic and vastly changing landscape, it was essential for our teams, both research and clinical, to come together and develop a forum in which all new cell therapies are discussed and vetted. Intervention In order to facilitate this multi-disciplinary cell therapy forum, we instituted the Immune Effector Cell (IEC) Committee. The IEC committee started as a pre-start-up review panel that focused on feasibility of trial conductivity and ensuring appropriate resources and processes were in place for each trial. The IEC committee has now evolved into a formal Disease Working Group (DWG) responsible for the review of all open trials in the cell therapy space, deviation review and reporting, enrollment and accrual management, and patient safety in addition to feasibility and care algorithm management. The IEC DWG meets monthly. Members include clinicians, dedicated cell therapy research staff, pharmacists, laboratory personnel and cancer center leadership. Discussion/Implications The new era of cellular immunotherapy is challenging current clinical trial oversight and workflow development to ensure novel therapies are transitioned seamlessly into clinical care. Developing a structured, multidisciplinary IEC DWG with supervision over all cell therapy clinical research serves as a foundation for innovative, quality care. This forum's assessment of upfront workload promotes synergy with all teams supporting cell therapy including research, apheresis, cell processing, inpatient and outpatient clinical programs. The IEC DWG infrastructure is a supportive environment for solid tumor cell therapy to integrate into the existing clinical framework. Future work at our institution includes a standard site readiness tool to facilitate communication and integration.

An initiative to improve equity, timeliness and access to District Health Board-funded physiotherapy in Canterbury, Christchurch, New Zealand.

Background and context General practice teams frequently request orthopaedic and musculoskeletal physiotherapy. In the Canterbury District Health Board (DHB) region, before November 2018, the criteria for DHB-funded physiotherapy were unclear. Wait times were many months. Care was provided on hospital sites. Limited data were available about the service. Assessment of problem A clinical project group including private and DHB hospital physiotherapists and general practitioners was established. Patients requiring orthopaedic and musculoskeletal physiotherapy who had certain criteria were seen by physiotherapists in contracted private clinics in the community instead of by physiotherapists in hospital departments. Patients received up to NZ$300 (excluding GST) of care. A claiming process was established that required the physiotherapy clinics to provide data on patient outcomes. Results In the first 12 months of the programme, 1229 requests were accepted. Patients waited an average of 11.1 days for their first appointment. There was an average Patient Specific Functional Scale increase of 3.7 after treatment. Strategies for improvement A change environment was critical for this community-based, geographically distributed model to succeed. It was supported by key clinicians and funders with sufficient authority to make changes as required. It required ongoing clinical oversight and operational support. Lessons DHB orthopaedic and musculoskeletal physiotherapy can be moved from hospital sites to a community-based, distributed service in a timely, effective and equitable fashion. There was a prompt time to treatment. Data collection was improved by tracking 'before' and 'after' measures.

Usability of a Wrist-Worn Smartwatch in a Direct-to-Participant Randomized Pragmatic Clinical Trial

Background: The availability of a wide range of innovative wearable sensor technologies today allows for the ability to capture and collect potentially important health-related data in ways not previously possible. These sensors can be adopted in digitalized clinical trials, i.e., clinical trials conducted outside the clinic to capture data about study participants in their day-to-day life. However, having participants activate, charge, and wear the digital sensors for long hours may prove to be a significant obstacle to the success of these trials. Objective: This study explores a broad question of wrist-wearable sensor effectiveness in terms of data collection as well as data that are analyzable per individual. The individuals who had already consented to be part of an asymptomatic atrial fibrillation screening trial were directly sent a wrist-wearable activity and heart rate tracker device to be activated and used in a home-based setting. Methods: A total of 230 participants with a median age of 71 years were asked to wear the wristband as frequently as possible, night and day, for at least a 4-month monitoring period, especially to track heart rhythm during sleep. Results: Of the individuals who received the device, 43% never transmitted any data. Those who used the device wore it a median of ∼15 weeks (IQR 2–24) and for 5.3 days (IQR 3.2–6.5) per week. For rhythm detection purposes, only 5.6% of all recorded data from individuals were analyzable (with beat-to-beat intervals reported). Conclusions: This study provides some important learnings. It showed that in an older population, despite initial enthusiasm to receive a consumer-quality wrist-based fitness device, a large proportion of individuals never activated the device. However, it also found that for a majority of participants it was possible to successfully collect wearable sensor data without clinical oversight inside a home environment, and that once used, ongoing wear time was high. This suggests that a critical barrier to overcome when incorporating a wearable device into clinical research is making its initiation of use as easy as possible for the participant.

Effects of Virtual Exercise Rehabilitation In-Home Therapy Compared with Traditional Care After Total Knee Arthroplasty

Financial burden for patients, providers, and payers can reduce access to physical therapy (PT) after total knee arthroplasty (TKA). The purpose of the present study was to examine the effect of a virtual PT program on health-care costs and clinical outcomes as compared with traditional care after TKA. At least 10 days before unilateral TKA, patients from 4 clinical sites were enrolled and randomized 1:1 to the virtual PT program (involving an avatar [digitally simulated] coach, in-home 3-dimensional biometrics, and telerehabilitation with remote clinician oversight by a physical therapist) or to traditional PT care in the home or outpatient clinic. The primary outcome was total health-care costs for the 12-week post-hospital period. Secondary (noninferiority) outcomes included 6 and 12-week Knee injury and Osteoarthritis Outcome Score (KOOS); 6-week knee extension, knee flexion, and gait speed; and 12-week safety measures (patient-reported falls, pain, and hospital readmissions). All outcomes were analyzed on a modified intent-to-treat basis. Of 306 patients (mean age, 65 years; 62.5% women) who were randomized from November 2016 to November 2017, 290 had TKA and 287 (including 143 in the virtual PT group and 144 in the usual care group) completed the trial. Virtual PT had lower costs at 12 weeks after discharge than usual care (median, $1,050 compared with $2,805; p < 0.001). Mean costs were $2,745 lower for virtual PT patients. Virtual PT patients had fewer rehospitalizations than the usual care group (12 compared with 30; p = 0.007). Virtual PT was noninferior to usual PT in terms of the KOOS at 6 weeks (difference, 0.77; 90% confidence interval [CI], -1.68 to 3.23) and 12 weeks (difference, -2.33; 90% CI, -4.98 to 0.31). Virtual PT was also noninferior to usual care at 6 weeks in terms of knee extension, knee flexion, and gait speed and at 12 weeks in terms of pain and hospital readmissions. Falls were reported by 19.4% of virtual PT patients and 14.6% of usual care patients (difference, 4.83%; 90% CI, -2.60 to 12.25). Relative to traditional home or clinic PT, virtual PT with telerehabilitation for skilled clinical oversight significantly lowered 3-month health-care costs after TKA while providing similar effectiveness. These findings have important implications for patients, health systems, and payers. Virtual PT with clinical oversight should be considered for patients managed with TKA. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Real-World Treatment Patterns and Clinical Outcomes in Multiple Myeloma in the Asia-Pacific Region: Methodology and Preliminary Results of the Asia-Pacific Myeloma and Related Diseases Registry (APAC MRDR)

Real-World Treatment Patterns and Clinical Outcomes in Multiple Myeloma in the Asia-Pacific Region: Methodology and Preliminary Results of the Asia-Pacific Myeloma and Related Diseases Registry (APAC MRDR)

Understanding geographical patterning of self-harm prevalence within a diverse urban population: a mixed methods spatial analysis and qualitative study

BackgroundPublic health understanding of variations in self-harm prevalence between populations largely relies on routinely collected service-use data. An unexpectedly low number of hospital inpatient admissions following self-harm has been observed in inner London despite established associations of area deprivation and social fragmentation with self-harm. We aimed to measure associations between rates of attendance at an Emergency Department following self-harm and area characteristics, and to explore the processes that might underlie the incidence of self-harm observed in inner inner-city areas. MethodFor the spatial analysis, we created a dataset of Emergency Department attendances following self-harm from 2009 to 2016 by residents of four southeast London boroughs who were older than 11 years using linked electronic patient record data and Hospital Episode Statistics. Age-standardised and sex-standardised small-area rates of self-harm attendance (SARs) were spatially smoothed using Bayesian models and mapped. Associations with area deprivation (assessed using the Index of Multiple Deprivation) and social fragmentation (Congdon Index) were analysed. For the qualitative study, we identified a case-study area from within the four boroughs studied of four contiguous census lower super output areas (LSOAs; approximately 2600 households that were both in the most deprived quintile of areas in the UK and had below average SARs for self-harm). We undertook semi-structured interviews with 14 individuals working in community organisations and two focus groups of 12 people older than 16 years and resident in the study area, recruited through community organisations. Ethical approval for data access and linkage was granted by the Oxford Research Ethics Committee C, Clinical Records Interactive Search system Oversight Committee, and the NHS Health Research Authority Confidentiality Advisory Group. The qualitative study was given ethical approval by the King's College London, Psychiatry, Nursing and Midwifery Subcommittee. FindingsWe identified 20 750 Emergency Department attendances following self-harm by 12 577 individuals. The ratio of SARs in the highest versus the lowest 5% of areas was 2·87 (95% credible interval [CrI] 2·65–3·13). Associations with self-harm were found for area deprivation (most vs least deprived quintile: rate ratio 2·07, 95% CrI 1·88–2·26) and social fragmentation (1·39, 1·23–1·56); however, we identified clusters of deprived areas with a low incidence of self-harm Emergency Department attendance. Preliminary qualitative analysis suggests that individuals in the case-study population have substantial cumulative stressors and mental health difficulties despite a low incidence of Emergency Department presentation for self-harm (SARs for the four LSOAs ranged from 0·80 to 0·94 before adjustment for deprivation and 0·68–0·81 after adjustment). Frequent experiences of violence and an emphasis on appearing tough combine with discomfort with talking about self-harm and fear of negative treatment by mental health and other services, particularly within the Caribbean and African population who make up 44% of the local population. These factors might make people more likely to respond to distress in ways not defined by researchers as self-harm (even if they are also damaging); equally, these pressures might make individuals who self-harm less likely to identify themselves to services. InterpretationRelying on service-use data for self-harm risks underestimating the extent of distress and subsequent harmful behaviours in some deprived urban populations already disadvantaged by high levels of violence and minority ethnic and migrant status. FundingNational Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.

Adverse life experiences and triggers for self-harm in young people aged 12–26 years in inner south London: a retrospective observational study

BackgroundThe prevalence of self-harm among children and young people in the UK is increasing, with few accessing formal support. Drivers of self-harm remain poorly understood, and evidence-based opportunities to intervene are scarce. We aimed to identify factors associated with self-harm in young people to inform local action. MethodsIn this retrospective, observational study, we identified 196 residents of the south London Borough of Lambeth, aged 12–26 years, presenting to two emergency departments for injuries related to self-harm in the 2015–16 financial year (April 1, 2015, to March 31, 2016). A pragmatic sample size of 100 was selected via computer randomisation for further analysis. Electronic mental health records were retrospectively analysed using a data collection protocol that was validated with researchers before data collection. Demographics and psychiatric history were obtained from pre-coded databases linking electronic mental health records and Hospital Episode Statistics data on emergency department attendance for self-harm. Presentation details and social risk factors were derived from assessment of case notes pertaining to the 2 weeks after first presentation; we noted any risk factors that had been positively recorded. Data relating to the individual's first presentation within the study period were used; subsequent attendances were not included in the sample. We analysed the data using descriptive statistics. Ethical approval for data access and linkage was granted by the Oxford Research Ethics Committee C (18/SC/0372), Clinical Records Interactive Search system Oversight Committee (project numbers 14–026 and 19–004), and the National Health Service (NHS) Health Research Authority Confidentiality Advisory Group (reference ECC 3–04(f)/2011). This study received approval as an audit project through Southwark Operational Directorate in the South London and Maudsley Foundation NHS Trust. Findings48 (48%) of the 100 selected participants had documented experience of psychological trauma, including exposure to violence. 18 (18%) lived in unstable accommodation, and 20 (20%) were known to social services. Difficulties at home (16 [16%]) and stress relating to housing, school, or financial pressures (13 [13%]) were common documented triggers for the self-harm episode at presentation. Peer influence was rarely noted, although 27 (27%) had recorded experience of bullying. InterpretationAdverse life experiences were prevalent and align with wider population prevalence estimates. Common triggers for self-harm relate to home and school environment and wider socioeconomic stressors, supporting the link between wider determinants of health and self-harm, and contributing to the case for public health action. Risk factors and triggers identified provide potential areas for additional targeted support to prevent development or escalation of self-harm behaviours. FundingUK National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and King's College London.

A third trial oversight committee: Functions, benefits and issues.

Background/aims:Clinical trial oversight is central to the safety of participants and production of robust data. The United Kingdom Medical Research Council originally set out an oversight structure comprising three committees in 1998. The first committee, led by the trial team, is hands-on with trial conduct/operations (‘Trial Management Group’) and essential. The second committee (Data Monitoring Committee), usually completely independent of the trial, reviews accumulating trial evidence and is used by most later phase trials. The Independent Data Monitoring Committee makes recommendations to the third oversight committee. The third committee, (‘Trial Steering Committee’), facilitates in-depth interactions of independent and non-independent trial members and gives broader oversight (blinded to comparative analysis). We investigated the roles and functioning of the third oversight committee with multiple research methods. We reflect upon these findings to standardise the committee’s remit and operation and to potentially increase its usage.Methods:We utilised findings from our recent published suite of research on the third oversight committee to inform guideline revision. In brief, we conducted a survey of 38 United Kingdom–registered Clinical Trials Units, reviewed a cohort of 264 published trials, observed 8 third oversight committee meetings and interviewed 52 trialists. We convened an expert panel to discuss third oversight committees. Subsequently, we interviewed nine patient/lay third committee members and eight committee Chairs.Results:In the survey, most Clinical Trials Units required a third committee for all their trials (27/38, 71%) with independent members (ranging from 1 to 6). In the survey and interviews, the independence of the third committee was valued to make unbiased consideration of Independent Data Monitoring Committee recommendations and to advise on trial progress, protocol changes and recruitment issues in conjunction with the trial leadership. The third committee also advised funders and sponsors about trial continuation and represented patients and the public by including lay members. Of the cohort of 264 published trials, 144 reported a ‘steering’ committee (55%), but the independence of these members was not described so these may have been internal Trial Management Groups. Around two thirds of papers (60%) reported having an Independent Data Monitoring Committee and 26.9% neither a steering nor an Independent Data Monitoring Committee. However, before revising the third committee charter (Terms of Reference), greater standardisation is needed around defining member independence, composition, primacy of decision-making, interactions with other committees and the lifespan.Conclusion:A third oversight committee has benefits for trial oversight and conduct, and a revised charter will facilitate greater standardisation and wider adoption.

Reboot Online: A Randomized Controlled Trial Comparing an Online Multidisciplinary Pain Management Program with Usual Care for Chronic Pain.

Chronic pain is a prevalent and burdensome condition. Reboot Online was developed to address treatment barriers traditionally associated with accessing face-to-face chronic pain management programs. It is a comprehensive multidisciplinary online treatment program, based on an existing and effective face-to-face multidisciplinary pain program (the Reboot program). A CONSORT-compliant randomized controlled trial was conducted, enrolling adults who had experienced pain for three months or longer. Participants were randomly allocated to either an eight-lesson multidisciplinary pain management program, Reboot Online (N = 41), or to a usual care (UC) control group (N = 39). Clinical oversight was provided by a multidisciplinary team remotely, including physiotherapists and clinical psychologists. Participants were measured at baseline, post-treatment (week 16), and three-month follow-up (week 28). Intention-to-treat analyses revealed that Reboot Online was significantly more effective than UC at increasing pain self-efficacy (g = 0.69) at post-treatment, and these gains were maintained at follow-up. Similarly, Reboot Online was significantly more effective than UC on several secondary measures at post-treatment and follow-up, including movement-based fear avoidance and pain-related disability, but it did not significantly reduce pain interference or depression compared with UC. Clinician input was minimal, and adherence to Reboot Online was moderate, with 61% of participants (N = 25) completing all eight lessons. Reboot Online presents a novel approach to multidisciplinary pain management and offers an accessible, efficacious alternative and viable treatment option for chronic pain management.

Patient experiences of ART adherence clubs in Khayelitsha and Gugulethu, Cape Town, South Africa: A qualitative study.

BackgroundGlobally, 37 million people are in need of lifelong antiretroviral treatment (ART). With the continual increase in the number of people living with HIV starting ART and the need for life-long retention and adherence, increasing attention is being paid to differentiated service delivery (DSD), such as adherence clubs. Adherence clubs are groups of 25–30 stable ART patients who meet five times per year at their clinic or a community location and are facilitated by a lay health-care worker who distributes pre-packed ART. This qualitative study explores patient experiences of clubs in two sites in Cape Town, South Africa.MethodsA total of 144 participants took part in 11 focus group discussions (FGDs) and 56 in-depth interviews in the informal settlements of Khayelitsha and Gugulethu in Cape Town, South Africa. Participants included current club members, stable patients who had never joined a club and club members referred back to clinician-led facility-based standard care. FGDs and interviews were conducted in isiXhosa, translated and transcribed into English, entered into NVivo, coded and thematically analysed.ResultsThe main themes were 1) understanding and knowledge of clubs; 2) understanding of and barriers to enrolment; 3) perceived benefits and 4) perceived disadvantages of the clubs. Participants viewed membership as an achievement and considered returning to clinician-led care a ‘failure’. Moving between clubs and the clinic created frustration and broke down trust in the health-care system.ConclusionsAdherence clubs were appreciated by patients, particularly time-saving in relation to flexible ART collection. Improved patient understanding of enrolment processes, eligibility and referral criteria and the role of clinical oversight is essential for building relationships with health-care workers and trust in the health-care system.

Cross-Coverage Care at a Crossroads.

Cross-Coverage Care at a Crossroads.

Entrustment Ratings in Internal Medicine Training: Capturing Meaningful Supervision Decisions or Just Another Rating?

The implementation of Entrustable Professional Activities has led to the simultaneous development of assessment based on a supervisor's entrustment of a learner to perform these activities without supervision. While entrustment may be intuitive when we consider the direct observation of a procedural task, the current implementation of rating scales for internal medicine's non-procedural tasks, based on entrustability, may not translate into meaningful learner assessment. In these Perspectives, we outline a number of potential concerns with ad hoc entrustability assessments in internal medicine post-graduate training: differences in the scope of procedural vs. non-procedural tasks, acknowledgement of the type of clinical oversight common within internal medicine, and the limitations of entrustment language. We point towards potential directions for inquiry that would require us to clarify the purpose of the entrustability assessment, reconsider each of the fundamental concepts of entrustment in internal medicine supervision and explore the use of descriptive rather than numeric assessment approaches.

PO 8381 REGULATING CLINICAL TRIALS DURING AN EBOLA EMERGENCY: THE LIBERIAN EXPERIENCE

BackgroundEffective clinical trials oversight is a major function of a fully functional national medical products regulatory system. However, exercising clinical trial oversight in a resource-limited environment is challenging, in particular during an Ebola outbreak or health emergency. Until the devastating Ebola virus disease (EVD) outbreak in 2014, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) had no capacity for effective clinical trial regulation. This presentation describes the main challenges encountered by LMHRA in regulating clinical trials in Liberia during the largest EVD outbreak that affected West Africa in 2014 and 2015.MethodsBy carefully documenting activities during the EVD outbreak, interviewing key stakeholders, and discussions among the LMHRA clinical trial committee, key challenges observed during the outbreak were identified and documented.ResultsLimited financial resources, lack of expertise in clinical trials, inaccurate and insufficient information about the functions of the LMHRA, poor coordination among key stakeholders, and the lack of a well-developed regulatory framework, adversely influenced the LMHRA clinical trial oversight performance during the EVD outbreak.ConclusionIt is true that several challenges need to be addressed when regulating a clinical trial in a limited-resource environment during any disease outbreak or international medical emergency. However, the importance of building local expertise in clinical trials through mentorship and training cannot be overemphasised. By taking advantage of grants from developmental partners, national medicines regulatory authorities in resource-limited environments can develop capacity for clinical research oversight.

PO 8300 REGIONAL CENTER FOR REGULATORY EXCELLENCE IN CLINICAL TRIAL OVERSIGHT – TRAINING 2017

BackgroundThe competencies of the various national medicines regulatory agencies (NMRAs) in Africa vary which leads to generally porous regulatory systems for clinical trial oversight. Consequently, many trials have been conducted under unacceptable conditions compromising participants’ safety and data credibility and resulted in questionable outcomes that are used for making scientific judgement in addressing issues of public health in Africa.To improve the safety and quality of health technologies in Africa, the New Partnership for African Development (NEPAD) agency launched a programme to designate Regional Centres of Regulatory Excellence (RCOREs) with the specific objective of bridging existing gaps between African NMRAs through strengthening regulatory capacity of African Union member states. The Food and Drugs Authority (FDA), Ghana, was designated as RCORE for Clinical Trials oversight in May 2014.MethodsTo achieve the RCORE objectives, the FDA collaborated with the School of Public Health (SPH), University of Ghana to develop a training manual and piloted a training programme with funds from the International AIDS Vaccine Initiative (IAVI) through NEPAD.The programme, consisting of 4 compulsory modules, was organised from 6–30 November 2017 for 10 participants from Zambia, Sierra Leone, Liberia, Rwanda and Ghana. Interactive training methods in the form of theoretical and practical sessions were employed.ResultsThe pilot RCORE training was successful with expected training objectives achieved. Participants gained hands-on experience through activities like observing Good Clinical Practice inspection and a Technical Advisory Committee Meeting. Participants were given template tools to assist in developing regulatory guidelines and forms in their respective countries.A follow-up questionnaire was circulated to participants to assess the impact of the training on their work. Feedback „indicates that regulation of clinical trials has improved in their respective institutions.ConclusionThis pilot fellowship training was successful, „leading to the improvement of clinical trial regulation in the participating countries.

Mental health screening for children in care using the Strengths and Difficulties Questionnaire and the Brief Assessment Checklists: Guidance from three national studies

Although children residing in statutory out-of-home care and those adopted from care are more likely than not to have mental health difficulties requiring clinical intervention or support, their difficulties often remain undetected. Children’s agencies have a duty of care to identify those child clients who require therapeutic and other support services, without regard to the availability of such services. The present article proposes a first-stage mental health screening procedure (calibrated for high sensitivity) for children and adolescents (ages 4–17) in alternative care, which children’s agencies can implement without clinical oversight using the Strengths and Difficulties Questionnaire (SDQ) and Brief Assessment Checklists (BAC). The screening procedure was derived from analyses of BAC, SDQ, and “proxy SDQ” scores obtained in three national studies of children and adolescents residing in alternative care (Australia, the Netherlands, and England). The SDQ and BAC demonstrated moderate to high screening accuracy across a range of clinical case criteria—the SDQ being slightly better at predicting general mental health problems and the BAC slightly better at predicting attachment- and trauma-related problems. Accurate first-stage screening is achieved using either the SDQ or the BAC alone, with recommended cut points of 10 (i.e., positive screen is 10 or higher) for the SDQ and 7 for the BAC. Greater accuracy is gained from using the SDQ and BAC in parallel, with positive screens defined by an SDQ score of 11 or higher or a BAC score of 8 or higher. Agencies and post-adoption support services should refer positive screens for comprehensive mental health assessment by clinical services.

Psychiatric Emergencies in Nonpsychiatric Settings: Perception Precludes Preparedness

The implementation of emergency codes has become standard practice in hospitals to provide system-wide preparedness for the early detection and prevention of crises. Psychiatric emergencies in medical/surgical locations, however, are not typically regarded as distinct entities from general security threats. The "security-first" paradigm is a nonclinical intervention that focuses on behavioral containment rather than onthe treatment of underlying psychopathology. This article provides the perspective that countless opportunities to medically intervene upon mental health emergencies are being overlooked due to a national misconception of these entities as security-based functions. A secondary consequence of this misperception is that hospital systems often fail to prioritize an infrastructure onto which clinically-informed emergency response protocols similar to other medical emergency codes may be dependably mounted in the event of accurately detecting psychiatric emergencies. Numerous adverse clinical, workplace safety, and financial outcomes ensue. Using a behavioral emergency response team as a collaborative care model in medical/surgical locations is a promising alternative. Behavioral emergency response teams re-establish patient care within the intervention without omitting security containment. They help rapidly address acute comorbid psychiatric needs without demanding additional psychiatric resources by functioning as trained surrogates of consult-liaison psychiatry as they provide direct clinical oversight into primary teams who would otherwise be unsupported in navigating clinical scenarios extending beyond their typical range of expertise. An analysis using the "Swiss cheese" model of human error trapping offers a comprehensive illustration of how behavioral emergency response teams add multilayered perceptual and mechanistic advantages to barriers commonly encountered when psychiatric emergencies arise in nonpsychiatric settings.