Evaluation of Global Post-Outbreak COVID-19 Treatment Interventions: A Systematic Review and Bibliometric Analysis of Randomized Controlled Trials

Mohammed Alfaqeeh,1 Neily Zakiyah,1,2 Auliya A Suwantika,1– 3 Zahratu Shabrina4,5 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia; 2Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, Indonesia; 3Center for Health Technology Assessment, Universitas Padjadjaran, Bandung, Indonesia; 4Department of Geography, King’s College London, London, UK; 5Regional Innovation, Graduate School, Universitas Padjadjaran, Bandung, IndonesiaCorrespondence: Neily Zakiyah, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, 45363, Indonesia, Tel +62 22 84288888, Ext. 3510, Email [email protected]: The outbreak of COVID-19 has led to a global pandemic with millions of cases and deaths. Many randomized controlled trials (RCTs) were conducted to establish effective therapies. However, the methodological quality of these trials is paramount, as it directly impacts the reliability of results. This systematic review and bibliometric analysis aim to assess the methodological approach, execution diversity, global trends, and distribution of COVID-19 treatment RCTs post-outbreak, covering the period from the second wave and onward up to the present.Methods: We utilize articles from three electronic databases published from September 1, 2020, to April 1, 2023. Inclusion and exclusion criteria were applied to identify relevant RCTs. Data extraction involved the collection of various study details. Risk of Bias (RoB) 2 tool assessed methodological quality, while implementation variability was evaluated against registration information. Bibliometric analysis, including keyword co-occurrence and country distribution, used VOSviewer and Tableau software.Results: Initially, 501 studies were identified, but only 22 met the inclusion criteria, of which 19 had registration information. The methodological quality assessment revealed deficiencies in five main domains: randomization process (36%), deviations from intended interventions (9%), missing outcome data (4%), measurement of the outcome (18%), and selection of reported results (4%). An analysis of alignment between research protocols and registration data revealed common deviations in eight critical aspects. Bibliometric findings showcased global collaboration in COVID-19 treatment RCTs, with Iran and Brazil prominently contributing, while keyword co-occurrence analysis illuminated prominent research trends and terms in study titles and abstracts.Conclusion: This study offers valuable insights into the evaluation of COVID-19 treatment RCTs. The scarcity of high-quality RCTs highlights the importance of enhancing trial rigor and transparency in global health emergencies.Keywords: COVID-19, randomized controlled trials, methodological quality, diversity in execution, keyword trends, geographic distributio

The Cost-Effectiveness of Dolutegravir in Combination with Tenofovir and Lamivudine for HIV Therapy: A Systematic Review

Santi Aprilianti,1,* Auliasari M Utami,1 Auliya A Suwantika,1– 3,* Neily Zakiyah,1,2,* Vanji Ikhsan Azis4 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia; 2Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Bandung, Indonesia; 3Center for Health Technology Assessment, Universitas Padjadjaran, Bandung, Indonesia; 4Research and Development, PT Kimia Farma Tbk, Bandung, Indonesia*These authors contributed equally to this workCorrespondence: Auliya A Suwantika, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Ir. Soekarno KM.21, Jatinangor, 45363, Indonesia, Email [email protected]: The World Health Organization (WHO) recommends dolutegravir (DTG), a human immunodeficiency virus (HIV) medicine, as the first- and second-line treatment for all populations because, when compared to an efavirenz (EFV) regimen, plus two nucleoside reverse transcriptase inhibitors (NRTIs) has demonstrated significant effectiveness in HIV suppression in persons. This study aims to review evidence of the cost-effectiveness of DTG in combination with tenofovir and lamivudine compared with the standard of care for HIV therapy. The systematic review involved searching electronic databases for articles published between January 2018 and May 2022. Electronic database sources include PubMed, ScienceDirect, and EBSCO for articles on DTG in combination with tenofovir and lamivudine as subjects with cost-effectiveness outcomes. The inclusion criteria in this systematic review were studies about the cost-effectiveness analysis (CEA) of DTG in combination with tenofovir and lamivudine, written in English. A total of 145 articles were identified from three databases. After removing nine duplicates, 142 articles were screened by title and abstract, excluding 123 articles. After a full-text screening of 19 articles, five articles were selected for further analysis. Five articles reviewed in sub-Saharan Africa, India, and China implemented different modelling methods for CEA but produced similar results. The results of these studies demonstrate that it is more cost-effective than standard care for HIV treatment. The study conducted in sub-Saharan Africa from 2018 to 2020 showed a cost-effective result with disability-adjusted life years averted (DALY averted) by 83%; in India, it resulted in incremental cost-effectiveness ratio (ICER) $130 per year of live-saved (YLS); and a study in China found that dolutegravir plus tenofovir and lamivudine led to 0.006 incremental quality-adjusted life years (QALYs) with cost savings of $64. The DTG regimen is cost-effective and recommended for HIV therapy in all studies that provide results.Keywords: cost-effectiveness, antiretroviral therapy, human immunodeficiency virus, dolutegravir, efaviren

Impact of COVID-19 Pandemic on Routine Childhood Immunization Programs in Indonesia: Taking Rural and Urban Area into Account

Nur Rahayuningsih,1,2 Rano K Sinuraya,1,3,4 Yasmin Fatinah,1 Ajeng Diantini,1,4 Auliya A Suwantika1,4,5 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 2Faculty of Pharmacy, Universitas Bakti Tunas Husada, Tasikmalaya, Indonesia; 3Unit of Global Health, Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 4Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Sumedang, Indonesia; 5Center for Health Technology Assessment, Universitas Padjadjaran, Sumedang, IndonesiaCorrespondence: Rano K Sinuraya, Email [email protected]; [email protected]: To date, the primary global concern has revolved around addressing the COVID-19 pandemic. However, there is a growing awareness of the pandemic’s secondary impacts on critical aspects of healthcare, such as childhood immunization programs.Objective: This study aims to assess the impact of the COVID-19 pandemic on childhood immunization programs in Indonesia, with a specific focus on performance disparities between rural and urban areas. It considers factors like access, utilization, and program workload.Methods: Data were collected from primary health cares (PHCs) in two regions in West Java Province, Indonesia, representing rural and urban areas. A descriptive analysis was conducted to compare vaccination coverage, drop-out rates, and the ratio of vaccinators per dose from 2019 to 2021 in 40 and 22 PHCs for rural and urban areas, respectively. A general linear model was employed to evaluate the differences in these parameters over the three consecutive years.Results: The results indicate fluctuations in vaccine coverage over the three years, with the most significant impact observed in 2020, particularly in rural areas. Statistical analysis revealed a significant difference in routine immunization coverage, drop-out rates, and vaccinator ratios between rural and urban areas from 2019 to 2021 (p< 0.05). In 2021, both rural and urban areas displayed significant differences in performance parameters for routine immunization and COVID-19 vaccination (p< 0.05), except in terms of coverage for IPV and COVID-19 vaccination.Conclusion: The study highlights a reduction in routine immunization coverage during the pandemic, a concerning issue that increases the risk of vaccine-preventable diseases, particularly in rural areas.Keywords: immunization coverage, dropout rate, workload, primary healthcare center

Incidence, causative drugs, and economic consequences of drug-induced SJS, TEN, and SJS&ndash;TEN overlap and potential drug&ndash;drug interactions during treatment: a retrospective analysis at an Indonesian referral hospital

Rizky Abdulah,1 Tazkia F Suwandiman,1 Nadhira Handayani,1 Dika P Destiani,1 Auliya A Suwantika,1 Melisa I Barliana,2 Keri Lestari1 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, 2Department of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia Background: Stevens&ndash;Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute life-threatening adverse drug reactions (ADRs) that are commonly caused by medications. Apart from their contribution to morbidity and mortality, these diseases may also present substantial consequences on health care resources. In this study, we aimed to identify the incidence, causative drugs, and economic consequences of these serious ADRs and potential drug&ndash;drug interactions (DDIs) during treatment.Methods: A retrospective study that included 150 patients diagnosed with drug-induced SJS, SJS&ndash;TEN overlap, and TEN, from 2009 to 2013 in a referral hospital in West Java Province, Indonesia, was conducted to analyze the causative drugs, cost of illness (COI) as a representation of economic consequences, and potential DDIs during treatment.Results: The results showed that analgesic&ndash;antipyretic drugs were the most frequently implicated drugs. The COIs for SJS, SJS&ndash;TEN overlap, and TEN patients were 119.49, 139.21, and 162.08 US dollars per day, respectively. Furthermore, potential DDIs with several therapeutic medications and corticosteroids used to treat SJS, SJS&ndash;TEN overlap, and TEN were also identified.Conclusion: This study showed that analgesic&ndash;antipyretic was the major causative drug which contributed to SJS, SJS&ndash;TEN overlap, and TEN. Furthermore, our results also showed that SJS, SJS&ndash;TEN overlap, and TEN may cause considerable financial consequences to patients. Keywords: Stevens&ndash;Johnson syndrome, toxic epidermal necrolysis, adverse drug reactions, cost of illnes

Real-world data for health technology assessment for reimbursement decisions in Asia: current landscape and a way forward.

There is growing interest globally in using real-world data (RWD) and real-world evidence (RWE) for health technology assessment (HTA). Optimal collection, analysis, and use of RWD/RWE to inform HTA requires a conceptual framework to standardize processes and ensure consistency. However, such framework is currently lacking in Asia, a region that is likely to benefit from RWD/RWE for at least two reasons. First, there is often limited Asian representation in clinical trials unless specifically conducted in Asian populations, and RWD may help to fill the evidence gap. Second, in a few Asian health systems, reimbursement decisions are not made at market entry; thus, allowing RWD/RWE to be collected to give more certainty about the effectiveness of technologies in the local setting and inform their appropriate use. Furthermore, an alignment of RWD/RWE policies across Asia would equip decision makers with context-relevant evidence, and improve timely patient access to new technologies. Using data collected from eleven health systems in Asia, this paper provides a review of the current landscape of RWD/RWE in Asia to inform HTA and explores a way forward to align policies within the region. This paper concludes with a proposal to establish an international collaboration among academics and HTA agencies in the region: the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) working group, which seeks to develop a non-binding guidance document on the use of RWD/RWE to inform HTA for decision making in Asia

Factors associated with the opposition to COVID-19 vaccination certificates: a multi-country observational study from Asia

Background There are ongoing calls to harmonise and increase the use of COVID-19 vaccination certificates (CVCs) in Asia. Identifying groups in Asian societies who oppose CVCs and understanding their reasons can help formulate an effective CVCs policy in the region. However, no formal studies have explored this issue in Asia. Method The COVID-19 Vaccination Policy Research and Decision-Support Initiative in Asia (CORESIA) was established to address policy questions related to CVCs. An online cross-sectional survey was conducted from June to October 2021 in nine Asian countries. Multivariable logistical regression analyses were performed to identify potential opposers of CVCs. Results Six groups were identified as potential opposers of CVCs: (i) unvaccinated (Odd Ratio (OR): 2.01, 95% Confidence Interval (CI): 1.65-2.46); vaccine hesitant and those without access to COVID-19 vaccines; (ii) those not wanting existing NPIs to continue (OR: 2.97, 95% CI: 2.51-3.53); (iii) those with low level of trust in governments (OR: 1.25, 95% CI: 1.02-2.52); (iv) those without travel plans (OR: 1.58, 95% CI: 1.31-1.90); (v) those expecting no financial gains from CVCs (OR: 2.35, 95% CI: 1.98-2.78); and (vi) those disagreeing to use CVCs for employment, education, events, hospitality, and domestic travel. Conclusions Addressing recurring public health bottlenecks such as vaccine hesitancy and equitable access, adherence to policies, public trust, and changing the narrative from ‘societal-benefit’ to ‘personal-benefit’ may be necessary and may help increase wider adoption of CVCs in Asia