Establishing a novel partnership model to deploy health services for children with autism in a low-resource setting - experience from Sri Lanka.

Sri Lanka is representative of challenges faced by low-income and middle-income countries, including the rise in the prevalence of autism and the lack of sufficient autism-specific services in the state sectors. The experience in establishing a Center to provide services for children with autism in Northern Sri Lanka is described. Funding and resourcing were accessed through an innovative partnership-based public/non-governmental organisation/charity model, where service-based outcomes were the main objectives. This model, incorporating state institutions, local and international charity organisations, and volunteers, devised a bespoke approach to care provision using the available resources under the clinical supervision of a consultant psychiatrist and the administrative purview of the Regional Director of Health Services. The evolution of this Center into a Learning Health System is described, reflecting how a minimalistic partnership approach focused on the integration of existing organisations and services could be a feasible model for the delivery of high-quality healthcare in low-resource settings.

Potential Drug-Drug Interactions Among Hospitalised Elderly Patients in Northern Sri Lanka, A Lower Middle-Income Country: A Retrospective Analysis.

BACKGROUND AND OBJECTIVES: Elderly individuals are more vulnerable to potential drug-drug interactions (pDDIs) as age-related physiological changes, polypharmacy and hospitalisations are known to increase the risk of pDDIs. The aims of this study were to assess the impact of hospitalisation and other associated factors on pDDIs in elderly patients, in a resource-limited setting. METHODS: This is a retrospective analysis of data of elderly patients (aged ≥ 65 years) admitted to the medical units of Jaffna Teaching Hospital. Preadmission and post-admission data were collected from clinic and hospital records, respectively. The British National Formulary was used to identify and categorise pDDIs. Point prevalence of pDDIs in elderly patients and the total number of pDDIs before and after hospitalisation were estimated. Factors contributing to pDDIs were determined by univariate and multivariable logistic regression. RESULTS: Two hundred and eighty-eight hospitalised elderly patients with a median age of 71 years (interquartile range 67-76 years) showed a significant increase in the prevalence of pDDIs post-admission compared with the preadmission values (77.1% vs 61.5%; p < 0.001) associated with an increase in total pDDIs (377 vs 488; p < 0.001) where the majority (> 75%) were potential pharmacodynamic interactions. An unadjusted analysis showed a significant association between pDDI and polypharmacy [taking five or more medications] (odds ratio [OR] = 14.17; 95% confidence interval [CI] 7.41-27.10), the presence of more than three underlying medical conditions (OR 4.14; 95% CI 1.70-10.06), ischaemic heart disease (OR 3.25; 95% CI 1.78-5.94) and asthma (OR 8.14; 95% CI 2.46-26.88). However, when adjusted for confounders only polypharmacy (OR 14.10; 95% CI 6.50-30.60) and the presence of underlying asthma (OR 11.61; 95% CI 2.82-47.85) were associated with pDDIs. CONCLUSIONS: The prevalence of pDDIs among elderly patients was high and increased with hospital admissions. Polypharmacy and relevant comorbidities were contributory factors. Increased awareness of the potential for pDDIs through appropriate training and simple measures including a proper drug history, creating a bespoke pDDI list and frequent medication reviews by healthcare professionals would help to mitigate pDDIs in resource-limited and technology-limited settings.

Are the Current Processes and Regulations Fit for Purpose to Deliver Novel Therapies During Pandemics? A Perspective on COVID-19 from the UK.

The COVID-19 pandemic was the first 'stress test' to assess whether the current regulations in the United Kingdom (UK) are fit for purpose to develop novel therapies during pandemics. It saw innovations and collaborations across the spectrum of the drug development and regulatory pathways, including extraordinary collaborations between the various stakeholders involved in the process, the repositioning of medicines, the deployment of multi-arm, multi-interventional adaptive trials, the institution of operational simplicity and flexibility across various trial activities, and regulatory innovations. The question arises whether the innovative flexibilities and the urgency that were instituted could have resulted in compromises to the integrity of the process. An assessment of the conduct of the RECOVERY trial and the speedy approval of dexamethasone by the UK Medicines and Healthcare products Regulatory Agency demonstrates that no compromises were made to the ethical and scientific integrity of the process. Lessons learnt could be applied for future pandemics and to enhance R&D productivity and contribute to global health by improving access to medicines, especially in low- and middle-income countries and for neglected or rare diseases. What is needed is not a major transformation in the process but the flexible adaptation of existing regulations to reduce bureaucracy and handover times. Arriving at an optimal balance between scientific standards, regulations and commercial conflicts of interest will pose considerable challenges but what the COVID-19 pandemic has shown is that where there is will, there is always a way.

Ongoing and future COVID-19 vaccine clinical trials: challenges and opportunities.

Large-scale deployment of COVID-19 vaccines will seriously affect the ongoing phases 2 and 3 randomised placebo-controlled trials assessing SARS-CoV-2 vaccine candidates. The effect will be particularly acute in high-income countries where the entire adult or older population could be vaccinated by late 2021. Regrettably, only a small proportion of the population in many low-income and middle-income countries will have access to available vaccines. Sponsors of COVID-19 vaccine candidates currently in phase 2 or initiating phase 3 trials in 2021 should consider continuing the research in countries with limited affordability and availability of COVID-19 vaccines. Several ethical principles must be implemented to ensure the equitable, non-exploitative, and respectful conduct of trials in resource-poor settings. Once sufficient knowledge on the immunogenicity response to COVID-19 vaccines is acquired, non-inferiority immunogenicity trials-comparing the immune response of a vaccine candidate to that of an authorised vaccine-would probably be the most common trial design. Until then, placebo-controlled, double-blind, crossover trials will continue to play a role in the development of new vaccine candidates. WHO or the Council for International Organizations of Medical Sciences should define an ethical framework for the requirements and benefits for trial participants and host communities in resource-poor settings that should require commitment from all vaccine candidate sponsors from high-income countries.

Development of triglyceride-lowering drugs to address residual cardiovascular risk: strategic and clinical considerations.

The prevalence of hypertriglyceridaemia is high and growing in several parts of the world. Hypertriglyceridaemia has a well-defined association with the risk of atherosclerotic cardiovascular (CV) disease and triglycerides represent a potential target for drugs aimed at mitigating CV risk. So far, no triglyceride-lowering pharmacological strategy has succeeded in conclusively showing the ability to modify clinical outcomes. This article discusses strategic and clinical aspects of development of triglyceride-lowering drugs to address CV disease.