METHODS: Research impact of universal access and quality healthcare projects funded by the National Institutes of Health Malaysia were assessed based on the modified Payback Framework, addressing categories of informing policy, knowledge production, and benefits to health and health sector. For the HRPS process, the Child Health and Nutrition Research Initiative methodology was adapted and adopted, with the incorporation of stakeholder values using weights and monetary allocation survey. Workshop discussions and interviews with stakeholders and research groups were conducted to identify research gaps, with the use of conceptual frameworks to guide the search.

RESULTS: Seventeen ongoing and 50 completed projects were identified for research funding impact analysis. Overall, research fund allocation differed from stakeholders' expectation. For research impact, 48 out of 50 completed projects (96.0%) contributed to some form of policy-making efforts. Almost all completed projects resulted in outputs that contributed to knowledge production and were expected to lead to health and health sector benefits. The HRPS process led to the identification of research priority areas that stemmed from ongoing and new issues identified for universal access and quality healthcare.

METHOD: This study was conducted using an exploratory qualitative approach on purposely selected healthcare providers at primary healthcare clinics. Twenty focus group discussions and three in-depth interviews were conducted using a semi-structured interview guide. Consent was obtained prior to interviews and for audio-recordings. Interviews were transcribed verbatim and thematically analysed, guided by the Consolidated Framework for Implementation Research (CFIR), a framework comprised of five major domains promoting implementation theory development and verification across multiple contexts.

RESULTS: The study revealed via CFIR that most primary healthcare providers were receptive towards any proposed changes or intervention for the betterment of NCD care management. However, many challenges were outlined across four CFIR domains-intervention characteristics, outer setting, inner setting, and individual characteristics-that included perceived barriers to implementation. Perception of issues that triggered proposed changes reflected the current situation, including existing facilitating aspects that can support the implementation of any future intervention. The importance of strengthening the primary healthcare delivery system was also expressed.

METHODS: This observational study was conducted between December 2018 and October 2019 at 25 PHCs in three regions in Malaysia. Each PHC was linked to one or more hospitals, for referral of seropositive participants for confirmatory testing and pretreatment evaluation. Treatment was provided in PHCs for non-cirrhotic patients and at hospitals for cirrhotic patients.

RESULTS: During the study period, a total of 15 366 adults were screened at the 25 PHCs, using RDTs for HCV antibodies. Of the 2020 (13.2%) HCV antibody-positive participants, 1481/2020 (73.3%) had a confirmatory viral load test, 1241/1481 (83.8%) were HCV RNA-positive, 991/1241 (79.9%) completed pretreatment assessment, 632/991 (63.8%) initiated treatment, 518/632 (82.0%) completed treatment, 352/518 (68.0%) were eligible for a sustained virological response (SVR) cure assessment, 209/352 (59.4%) had an SVR cure assessment, and SVR was achieved in 202/209 (96.7%) patients. A significantly higher proportion of patients referred to PHCs initiated treatment compared with those who had treatment initiated at hospitals (71.0% vs 48.8%, p<0.001).

METHODS: STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.

FINDINGS: Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.

INTERPRETATION: In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.