UNASSIGNED: Targeted germline testing is recommended for those with or at risk of breast, ovarian, or colorectal cancer. The affordability of genetic sequencing has improved over the past decade, therefore the cost-effectiveness of testing for these cancers is worthy of reassessment.
UNASSIGNED: To systematically review economic evaluations on cost-effectiveness of germline testing in breast, ovarian, or colorectal cancer.
UNASSIGNED: A search of PubMed and Embase databases for cost-effectiveness studies on germline testing in breast, ovarian, or colorectal cancer, published between 1999 and May 2022. Synthesis of methodology, cost-effectiveness, and reporting (CHEERS checklist) was performed.
UNASSIGNED: The incremental cost-effectiveness ratios (ICERs; in 2021-adjusted US$) for germline testing versus the standard care option in hereditary breast or ovarian cancer (HBOC) across target settings were as follows: (1) population-wide testing: 344-2.5 million/QALY; (2) women with high-risk: dominant = 78,118/QALY, 8,337-59,708/LYG; (3) existing breast or ovarian cancer: 3,012-72,566/QALY, 39,835/LYG; and (4) metastatic breast cancer: 158,630/QALY. Likewise, ICERs of germline testing for colorectal cancer across settings were: (1) population-wide testing: 132,200/QALY, 1.1 million/LYG; (2) people with high-risk: 32,322-76,750/QALY, dominant = 353/LYG; and (3) patients with existing colorectal cancer: dominant = 54,122/QALY, 98,790-6.3 million/LYG. Key areas of underreporting were the inclusion of a health economic analysis plan (100% of HBOC and colorectal studies), engagement of patients and stakeholders (95.4% of HBOC, 100% of colorectal studies) and measurement of outcomes (18.2% HBOC, 38.9% of colorectal studies).
UNASSIGNED: Germline testing for HBOC was likely to be cost-effective across most settings, except when used as a co-dependent technology with the PARP inhibitor, olaparib in metastatic breast cancer. In colorectal cancer studies, testing was cost-effective in those with high-risk, but inconclusive in other settings. Cost-effectiveness was sensitive to the prevalence of tested variants, cost of testing, uptake, and benefits of prophylactic measures. Policy advice on germline testing should emphasize the importance of these factors in their recommendations.
Breast, ovarian, prostate, and colorectal cancers are among the top causes of cancer related deaths. A substantial proportion of people with these cancers have inherited mutations. The identification of these gene abnormalities could provide people with opportunities to utilize preventive risk reduction surgeries or undertake frequent routine testing for these cancers. However, genetic testing requires healthcare resources and money. Previous reviews on the cost-effectiveness of genetic testing in familial cancers have concluded that targeted screening i.e., selective assessment of people at high-risk could justify the costs of testing. Our evaluation of economic studies in breast and ovarian cancer, however, suggests that genetic testing is cost-effective across a wide variety of situations starting from the screening of all healthy women above 30 years to the testing of women with existing breast or ovarian cancer. Testing in metastatic breast cancer to inform treatment with Olaparib, a drug known to selectively improve survival in people with genetic mutations, was the sole exception where testing was not cost-effective. Contrary to findings for breast or ovarian cancer, testing for colorectal cancer was cost-effective in people with high-risk i.e., family history but inconclusive in other situations. Evidence on the cost-effectiveness of testing in prostate cancer is lacking and as a result we were not able to provide advice in this cancer group.

UNASSIGNED: Various methods exist for the induction of labor (IOL), and there is limited consensus as to optimal methods. Off-label misoprostol is recommended by the World Health Organization (WHO) for IOL but preparing it into doses suitable for IOL lacks precision, with potential adverse outcomes if dosing is inaccurate. This study explores potential outcomes and costs associated with increased uptake of a low-dose (25 µg) oral misoprostol formulation (Angusta; Norgine BV, Amsterdam) approved for IOL, in France, Belgium, and the Netherlands.
UNASSIGNED: A literature review was undertaken to derive probabilities of delivery outcomes (vaginal, instrumental, and cesarean sections) for IOL methods, from published meta-analyses. Outcomes for oral misoprostol tablets (25 µg) were unavailable in the meta-analyses, so were estimated using data from two published retrospective cohort studies. A model was developed to predict the frequency of IOL outcomes and associated costs at the national level, across multiple scenarios. Scenarios were tested using a moderate, medium, and high increase in oral misoprostol tablet (25 µg) uptake. Market shares, costs, and induction rates were defined for each country using multiple data sources.
UNASSIGNED: Increased uptake of oral misoprostol tablets (25 µg) was estimated to be associated with a slightly increased rate of routine vaginal deliveries, and concurrent decreases in instrumental vaginal deliveries and cesarean sections. Since routine vaginal deliveries are less costly than other delivery outcomes, increased uptake of oral misoprostol tablets (25 µg) within the IOL market has the potential to be cost-saving. These trends were predicted using 25 µg oral misoprostol tablet outcomes informed by both retrospective studies.
UNASSIGNED: Preliminary outcomes suggest that oral misoprostol tablets at 25 µg per dose may improve outcomes in IOL and be cost-saving. Further study is required to validate these findings and assess the comparative efficacy of IOL methods, including oral misoprostol tablets (25 µg).

UNASSIGNED: To perform a systematic review and meta-analysis to pool the incremental net benefit (INB) of each herpes zoster vaccine [i.e. Zoster Vaccine Live (ZVL) and Recombinant Zoster Vaccine (RZV)].
UNASSIGNED: We initially identified individual studies by hand-searching reference lists of the relevant systematic review articles. An updated comprehensive search was performed in Medline, Scopus, and Embase until June 2020 for additional studies. Studies were eligible if they assessed the cost-effectiveness/utility of any pair among ZVL and RZV, and no vaccine and reported economic outcomes. Details of the study characteristics, economic model inputs, costs, and outcomes were extracted. INB was calculated with monetary units adjusting for purchasing power parity for 2019 US dollars and pooled by meta-analysis.
UNASSIGNED: A total of 37 studies were pooled for meta-analysis stratified by perspectives [i.e. societal (SP) and third-party payer (TPP)] and vaccine types. In SP, ZVL was cost-effective compared to no vaccine when vaccinated at ages of 50-59 and 70-79 years with INBs (95% CI) of $0.61 (0.37, 0.85) and $9.67 (5.20, 14.14), respectively. RZV was cost-effective for those aged 60-69 and 70-79 years with INBs of $75.61 (17.98, 133.23) and $85.01 (30.02, 140.01), respectively. In TPP, ZVL was cost-effective compared to no vaccine when vaccinated at age 70-79 years with INB of $7.57 (0.27, 14.86) and RZV was cost-effective at 60-69 years with INB $220.87 (47.80, 393.93). The cost-effectiveness of RZV was robust across a series of sensitivity analyses, but ZVL differs on different vaccination ages.
UNASSIGNED: RZV may be cost-effective for vaccination in ages of 60-79 years for both SP and TPP perspectives, while ZVL might be cost-effective in some age groups, but results are not robust.

OBJECTIVE: To review the evidence supporting the validity of billing, procedural, or diagnosis code, or pharmacy claim-based algorithms used to identify patients with rheumatoid arthritis (RA) in administrative and claim databases.
METHODS: We searched the MEDLINE database from 1991 to September 2012 using controlled vocabulary and key terms related to RA and reference lists of included studies were searched. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria and extracted the data. Data collected included participant and algorithm characteristics.
RESULTS: Nine studies reported validation of computer algorithms based on International Classification of Diseases (ICD) codes with or without free-text, medication use, laboratory data and the need for a diagnosis by a rheumatologist. These studies yielded positive predictive values (PPV) ranging from 34 to 97% to identify patients with RA. Higher PPVs were obtained with the use of at least two ICD and/or procedure codes (ICD-9 code 714 and others), the requirement of a prescription of a medication used to treat RA, or requirement of participation of a rheumatologist in patient care. For example, the PPV increased from 66 to 97% when the use of disease-modifying antirheumatic drugs and the presence of a positive rheumatoid factor were required.
CONCLUSIONS: There have been substantial efforts to propose and validate algorithms to identify patients with RA in automated databases. Algorithms that include more than one code and incorporate medications or laboratory data and/or required a diagnosis by a rheumatologist may increase the PPV.

UDP-glucuronosyltransferases (UGT) catalyze the biotransformation of many endobiotics and xenobiotics, and are coded by polymorphic genes. However, knowledge about the effects of these polymorphisms is rarely used for the individualization of drug therapy. Here, we present a quantitative systematic review of clinical studies on the impact of UGT variants on drug metabolism to clarify the potential for genotype-adjusted therapy recommendations. Data on UGT polymorphisms and dose-related pharmacokinetic parameters in man were retrieved by a systematic search in public databases. Mean estimates of pharmacokinetic parameters were extracted for each group of carriers of UGT variants to assess their effect size. Pooled estimates and relative confidence bounds were computed with a random-effects meta-analytic approach whenever multiple studies on the same variant, ethnic group, and substrate were available. Information was retrieved on 30 polymorphic metabolic pathways involving 10 UGT enzymes. For irinotecan and mycophenolic acid a wealth of data was available for assessing the impact of genetic polymorphisms on pharmacokinetics under different dosages, between ethnicities, under comedication, and under toxicity. Evidence for effects of potential clinical relevance exists for 19 drugs, but the data are not sufficient to assess effect size with the precision required to issue dose recommendations. In conclusion, compared to other drug metabolizing enzymes much less systematic research has been conducted on the polymorphisms of UGT enzymes. However, there is evidence of the existence of large monogenetic functional polymorphisms affecting pharmacokinetics and suggesting a potential use of UGT polymorphisms for the individualization of drug therapy.