A systematic review of methodological approaches for evaluating real-world effectiveness of COVID-19 vaccines: Advising resource-constrained settings

Real-world effectiveness studies are important for monitoring performance of COVID-19 vaccination programmes and informing COVID-19 prevention and control policies. We aimed to synthesise methodological approaches used in COVID-19 vaccine effectiveness studies, in order to evaluate which approaches are most appropriate to implement in low- and middle-income countries (LMICs). For this rapid systematic review, we searched PubMed and Scopus for articles published from inception to July 7, 2021, without language restrictions. We included any type of peer-reviewed observational study measuring COVID-19 vaccine effectiveness, for any population. We excluded randomised control trials and modelling studies. All data used in the analysis were extracted from included papers. We used a standardised data extraction form, modified from STrengthening the Reporting of OBservational studies in Epidemiology (STROBE). Study quality was assessed using the REal Life EVidence AssessmeNt Tool (RELEVANT) tool. This study is registered with PROSPERO, CRD42021264658. Our search identified 3,327 studies, of which 42 were eligible for analysis. Most studies (97.5%) were conducted in high-income countries and the majority assessed mRNA vaccines (78% mRNA only, 17% mRNA and viral vector, 2.5% viral vector, 2.5% inactivated vaccine). Thirty-five of the studies (83%) used a cohort study design. Across studies, short follow-up time and limited assessment and mitigation of potential confounders, including previous SARS-CoV-2 infection and healthcare seeking behaviour, were major limitations. This review summarises methodological approaches for evaluating real-world effectiveness of COVID-19 vaccines and highlights the lack of such studies in LMICs, as well as the importance of context-specific vaccine effectiveness data. Further research in LMICs will refine guidance for conducting real-world COVID-19 vaccine effectiveness studies in resource-constrained settings.

Wooden sticks for plaque streaking and microbiological inoculation might be more cost- effective, but is its large scale use feasible? Quality control methods and proof of concept

The loop is a material classically used in the laboratory for the purpose of plate streaking and handling biological materials. However, metal loops techniques might be time consuming, considering the amount of time spent to guarantee its cooling process through each inoculation. Furthermore, plastic loops may also represent environmental issues during its production and discard process and can also represent higher costs for the laboratory. Thus, in situations of limited resources, even the simplest materials can be restricted due to logistical and budgetary issues, especially in developing countries. Inspired by demands like these, facing an occasional shortage of supply of laboratory plastic handles, we hereby present a quality control for sterilization methods and cost-effectiveness studies towards the use of wooden sticks in a Latin American country and we discuss the possibility of the large-scale use of this technique.

Cost-Effectiveness of Immune Checkpoint Inhibitors in Urothelial Carcinoma—A Review

Over the last decade, an increasing number of immune checkpoint inhibitors (ICIs) have been assessed for therapeutic efficacy in urothelial carcinoma (UC). The high cost has prompted multiple cost-effectiveness analyses for the various disease stages, with no established consensus. We reviewed the literature to assess the available cost-effectiveness studies and summarize their findings. Studies were filtered for a calculated incremental cost-effectiveness ratio (ICER) to standardize comparison. Over 2600 articles were narrowed to eight primary investigations: one for BCG-refractory non-muscle invasive (NMI), one for neoadjuvant therapy in muscle-invasive (MI), and six for advanced disease. Cost-effectiveness was not achieved for NMI disease. Atezolizumab met the willingness-to-pay (WTP) threshold as neoadjuvant therapy for MI disease compared to chemotherapy, but with multiple limitations on the interpretation. Of the six studies on advanced disease, the results were mixed. This was at least partially attributable to varied methodologies including extrapolated time horizons, inconsistent cost inputs, and different WTP thresholds. Overall, the aggregate results were not compelling enough to establish ICIs as cost-effective compared to conventional chemotherapy. Value may improve with continued investigation into long-term outcomes, refined patient selection, and pricing discounts.

Oral Cholera Vaccine Efficacy and Effectiveness

Although measuring vaccine efficacy through the conventional phase III study design, randomized, double-blinded controlled trial serves as the “gold standard”, effectiveness studies, conducted in the context of a public health program, seek to broaden the understanding of the impact of a vaccine in a real world setting including both individual and population level impacts. Cholera is an acute diarrheal infection caused by the ingestion of food or water contaminated with the bacterium Vibrio cholerae. Since the 1980s, either killed or live oral cholera vaccines (OCVs) have been developed and efficacy and effectiveness studies have been conducted on OCV. Although the results of OCV effectiveness studies sometimes showed outliers, the tendency seen is for effectiveness of the vaccine used in public health settings to be somewhat higher than estimated in randomized controlled trials due to the influence of indirect herd protection. Efficacy and Effectiveness studies both generate important information about the vaccine performance characteristics and its impact when used in real world populations at risk for the disease.

PP148 Liquid Biopsy For The Detection Of Ovarian Or Endometrial Cancer In Samples Taken From The Pap Smear: PapSEEK

IntroductionThe PapSEEK test is an emerging minimally invasive technique in which samples are collected from the endocervical or intrauterine cavity with the Papanicolaou (Pap) brush or the Tao brush to detect somatic mutations or aneuploidies indicating the presence of endometrial or ovarian cancer.MethodsWe systematically searched for articles published up to October 2020 in the following electronic databases: Medline, Embase, the Cochrane Library, and the Centre for Reviews and Dissemination. We included experimental studies, observational primary studies, and cost-effectiveness studies evaluating the safety, effectiveness, and cost effectiveness of the PapSEEK test for the early detection of ovarian or endometrial cancer. Relevant outcomes included sensitivity, specificity, the coefficient of variation, re-test rates, the incremental cost-effectiveness ratio, the incremental cost-utility ratio, and the cost of each alternative.ResultsA single relevant retrospective study was identified. In this study, samples from women with endometrial cancer (n = 656) and ovarian cancer (n = 254) were collected with the Pap brush and Tao brush and compared with samples from healthy women (n = 1,002). The diagnostic validity for somatic mutation or aneuploidies obtained with a Pap brush had a sensitivity of 81% for endometrial cancer and 33% for ovarian cancer, and a specificity of 99% for both conditions. When samples were collected from the intrauterine cavity with a Tao brush, the sensitivity increased to 93% for endometrial cancer and to 45% for ovarian cancer. The sensitivity of the PapSEEK test increased only for ovarian cancer when plasma samples to detect circulating tumor DNA were collected in addition to Pap smear samples. This strategy provided a diagnostic validity of 43%, which was higher in late-stage ovarian cancer (56% versus 35%), and a specificity of 100%.ConclusionsProspectively designed studies are required to assess the safety and effectiveness of the PapSEEK test in screening settings, as well as studies comparing the technology with conventional screening methods. No cost-effectiveness studies have been conducted for the PapSEEK test.

Comprehensive cost-effectiveness of diabetes management for the underserved in the United States: A systematic review

Background Diabetes mellitus affects almost 10% of U.S. adults, leading to human and financial burden. Underserved populations experience a higher risk of diabetes and related complications resulting from a combination of limited disposable income, inadequate diet, and lack of insurance coverage. Without the requisite resources, underserved populations lack the ability to access healthcare and afford prescription drugs to manage their condition. The aim of this systematic review is to synthesize the findings from cost-effectiveness studies of diabetes management in underserved populations. Methods Original, English, peer-reviewed cost-effectiveness studies of diabetes management in U.S. underserved populations were obtained from 8 databases, and PRISMA 2009 reporting guidelines were followed. Evidence was categorized as strong or weak based on a combination of GRADE and American Diabetes Association guidelines. Internal validity was assessed by the Cochrane methodology. Studies were classified by incremental cost-effectiveness ratio as very cost-effective (ICER≤US$25,000), cost-effective (US$25,000<ICER≤US$50,000), marginally cost-effective (US$50,000<ICER≤US$100,000) or cost-ineffective (ICER>US$100,000). Reporting and quality of economic evaluations was assessed using the CHEERS guidelines and Recommendations of Second Panel for Cost-Effectiveness in Health and Medicine, respectively. Findings Fourteen studies were included. All interventions were found to be cost-effective or very cost-effective. None of the studies reported all 24 points of the CHEERS guidelines. Given the considered cost categories vary significantly between studies, assessing cost-effectiveness across studies has many limitations. Program costs were consistently analyzed, and a third of the included studies (n = 5) only examined these costs, without considering other costs of diabetes care. Interpretation Cost-effectiveness studies are not based on a standardized methodology and present incomplete or limited analyses. More accurate assessment of all direct and indirect costs could widen the gap between intervention and usual care. This demonstrates the urgent need for a more standardized and comprehensive cost-effectiveness framework for future studies.

21. Systematic Review and Meta-Analysis of Pneumococcal Vaccine Effectiveness against Invasive Pneumococcal Disease among Adults

Background Two new pneumococcal conjugate vaccines (PCVs), PCV15 and PCV20, are anticipated to be licensed for use in U.S. adults in 2021. To help inform the U.S. Advisory Committee on Immunization Practices’ discussions on pneumococcal vaccine use among adults, we conducted a systematic review and meta-analysis. We specifically looked at efficacy or effectiveness of PCV13 and pneumococcal polysaccharide vaccine (PPSV23) against invasive pneumococcal disease (IPD) in adults. Methods We conducted a search of English literature published from 1998 – February 2021 on PCV13 and PPSV23 efficacy or effectiveness studies using eight major databases. Studies targeting adults with immunocompromising conditions were excluded. Title and abstract screening of identified studies and data abstraction were performed by two reviewers. Results were stratified by vaccine product, outcome evaluated (vaccine type (VT) or all IPD), study design, and effect measure. Random effects models were used to pool estimates by stratum. Results Of 3,422 citations reviewed, we identified 26 IPD studies; 4 on PCV13, 22 on PPSV23, 18 with all IPD, and 17 with VT-IPD (Table) as an outcome. Only one randomized-controlled trial (RCT) was identified for PCV13 with an efficacy of 52% (95% CI: 22%, 77%) against all IPD and 75% (95% CI: 41%, 91%) against VT-IPD. A pooled vaccine effectiveness (VE) estimate from three observational studies evaluating PCV13 was 56% (95% CI: 32%, 71%; I2 =12.8) against VT-IPD. Two RCTs evaluating PPSV23 reported efficacies against all IPD ranging between 79-86%; an additional RCT reported no IPD cases during RCT. Vaccine effectiveness estimates from 14 observational studies evaluating PPSV23 ranged between 29-76% against all IPD. Pooled VE estimates from 12 observational studies showed PPSV23 effectiveness against VT-IPD was 38% (95% CI: 28% to 46%; I2 =40.8). Table. Efficacy and effectiveness studies against vaccine-type invasive pneumococcal disease Conclusion Evidence suggests both pneumococcal vaccines are effective against VT-IPD in adults. Given that PCV15 and PCV20 are expected to be licensed based on immunogenicity data and no clinical efficacy data are available for these new vaccines, the findings from this review will help inform policy discussions on use of the new PCVs among adults. Disclosures All Authors: No reported disclosures