Dalia Dawoud

As the world edges towards relaxing the lockdown measures taken to control the spread of the novel coronavirus SARS-CoV-2 (COVID-19), governments have started putting in place a variety of measures to avoid a second peak in the number of infections. The implementation of and adherence to such measures will be key components of any successful lockdown exit strategy. Ranging from expanded testing and widespread use of technology to building the public's trust in the post COVID-19 world, there is a role for pharmacists to play. In this commentary, these measures and the potential contribution of pharmacists to their successful implementation are outlined and discussed.

Across the globe, pharmacists on the frontline continue to fight COVID-19 and its continuously evolving physical, mental, and economic consequences armed by their knowledge, professionalism, and dedication. Their need for credible scientific evidence to inform their practice has never been more urgent. Despite the exponentially increasing number of publications since the start of the pandemic, questions remain unanswered, and more are created, than have been resolved by the increasing number of publications. A panel of leading journal editors was convened by the International Pharmaceutical Federation (FIP) Pharmacy Practice Research Special Interest Group to discuss the current status of COVID-19 related research, provide their recommendations, and identify focal points for pharmacy practice, social pharmacy, and education research moving forward. Key priorities identified spanned a wide range of topics, reflecting the need for good quality research to inform practice and education. The panel insisted that a foundation in theory and use of rigorous methods should continue forming the basis of inquiry and its resultant papers, regardless of topic area. From assessing the clinical and cost effectiveness of COVID-19 therapies and vaccines to assessing different models of pharmaceutical services and education delivery, these priorities will ensure that our practice is informed by the best quality scientific evidence at this very challenging time.

OBJECTIVE: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents.

DESIGN: Multinational network cohort study.

SETTING: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea.

PARTICIPANTS: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020.

MAIN OUTCOME MEASURES: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19.

RESULTS: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020.

CONCLUSIONS: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.

Background Increasing evidence for the use of the aspirin in patients undergoing an orthopaedic surgery for venous thromboembolism prophylaxis has led to a change in the national guidelines substituting anticoagulants with aspirin. Little is known about the impact of such substitution on real-world outcomes from clinical practice. Objective The study was designed to examine clinical outcomes associated with the use of aspirin and apixaban. Setting Two large-scale general hospitals in West Yorkshire region of England. Method A 1-year observational study among adults who underwent elective knee replacements and received venous thromboembolism prophylaxis within the first 14 days post replacements. Main outcome measure The incidence of postoperative venous thromboembolism, leaking wounds during the hospital stay, and 30-day any readmission for the two drugs. Results A total of 420 patients were included. There was a significant drop in apixaban prescribing (from 80.37 to 10.51%) and increase in aspirin use (from 19.02 to 81.71%) after the implementation of the revised guidelines. There were 52 (12.38%) cases of leaking wound, 16 (3.81%) cases of postoperative venous thromboembolism, 45 (10.71%) cases of 30-day readmission and no case of 30-day major bleeding. The leaking wounds and 30-day readmissions were almost twice more frequent in obese compared to non-obese patients. Multivariate logistic regression found an increased risk of leaking wound with apixaban and postoperative venous thromboembolism and 30-day readmission with aspirin use but the differences were not statistically significant. Conclusion The results suggest aspirin to be as effective as apixaban in preventing venous thromboembolism and readmission. Apixaban usage decreased with a corresponding increase in Aspirin use. The impact of obesity and length of hospital stay need further investigations.

OBJECTIVE: To review published economic evaluations of antiviral treatment for pandemics and outbreaks of respiratory illnesses.

METHODS: We conducted a systematic review to identify economic evaluations of antiviral treatment for pandemics and outbreaks of respiratory illnesses, including coronavirus disease 2019 (COVID-19). We searched Medline (EBSCOhost), EMBASE (Ovid), EconLit (Ovid), National Health Service Economic Evaluation Database (Ovid), and Health Technology Assessment (Ovid). The search was last rerun on July 5, 2020. Citation tracking and reference checking were used. Only full economic evaluations published as peer-reviewed articles in the last 10 years were included. Studies were quality assessed using the National Institute for Health and Care Excellence economic evaluation checklist.

RESULTS: Overall, 782 records were identified, of which 14 studies met the inclusion criteria. The studies were mostly conducted in high-income countries. All were model-based. Seven (50%) were cost-utility analyses, 4 (28.6%) were cost-effectiveness analyses, 2 (14.3%) were cost-consequences analyses, and 1 (7.1%) was a cost-benefit analysis. Strategies including antiviral treatment were found to be either cost-saving or cost-effective, at the study-specific willingness-to-pay thresholds. Empirical treatment was more cost-effective than test-guided treatment for young adults but less so for older adults.

CONCLUSIONS: Antiviral treatment for managing pandemics and outbreaks of respiratory illnesses that have very high case fatality rate, similar to COVID-19 pandemic, are likely to be cost-effective either as a standalone intervention or part of a multifaceted strategy. Investing in the development of such curative treatments and promptly evaluating their cost-effectiveness, relative to other strategies in use at the time of their introduction should be the focus going forward to inform resource allocation decisions particularly in low- and middle-income countries.

The SF-6D is a preference-based measure of health developed to generate utility values from the SF-36. The aim of this pilot study was to examine the feasibility and acceptability of using the standard gamble (SG) technique to generate preference-based values for the Arabic version of SF-6D in a Lebanese population. The SF-6D was translated into Arabic using forward and backward translations. Forty-nine states defined by the SF-6D were selected using an orthogonal design and grouped into seven sets. A gender-occupation stratified sample of 126 Lebanese adults from the American University of Beirut were recruited to value seven states and the pits using SG. The sample size is appropriate for a pilot study, but smaller than the sample required for a full valuation study. Both interviewers and interviewees reported their understanding and effort levels in the SG tasks. Mean and individual level multivariate regression models were fitted to estimate preference weights for all SF-6D states. The models were compared with those estimated in the UK. Interviewers reported few problems in completing SG tasks (0.8% with a lot of problems) and good respondent understanding (5.6% with little effort and concentration), and 25% of respondents reported the SG task was difficult. A total of 992 SG valuations were useable for econometric modeling. There was no significant change in the test-retest values from 21 subjects. The mean absolute errors in the mean and individual level models were 0.036 and 0.050, respectively, both of which were lower than the UK results. The random effects model adequately predicts the SG values, with the worst state having a value of 0.322 compared to 0.271 in the UK. This pilot confirmed that it was feasible and acceptable to generate preference values with the SG method for the Arabic SF-6D in a Lebanese population. However, further work is needed to extend this to a more representative population, and to explore why no utility values below zero were observed.

In spite of concerns about the lack of recognition for its conduct, peer review remains the backbone of scientific evaluation and advancement of scientific knowledge. Given the challenges and evolution in the peer review system, collegiality among authors, reviewers, editors, and even consumers of content is more important than ever. While general guidance has been provided recently in the pharmacy literature, this commentary provides both philosophical underpinnings and specific mechanics for enhancing effectiveness of reviews and improving the quality of writing for authors concurrently, thus examining each major section in an original research contribution. Generosity, courtesy, diligence, thoroughness, and empathy are required of us all to advance the scientific paradigm of our discipline and profession.

INTRODUCTION: Oral isotretinoin is commonly prescribed for acne vulgaris. Several case reports and observational studies have reported serious musculoskeletal side effects; however, the incidence, imaging findings, and longitudinal follow-up data are limited for patients who develop inflammatory back pain (IBP).

OBJECTIVE: To assess the incidence of isotretinoin-triggered axial spondyloarthropathy (SpA) in acne vulgaris patients based on clinical features and MRI findings and to examine clinical and radiological outcomes following drug withdrawal.

METHODS: Five hundred thirteen acne patients receiving isotretinoin were screened for IBP; IBP patients were assessed for CRP, plain radiographs, and MRI of the sacroiliac joint. MRI-proven sacroiliitis was scored semi-quantitatively. Patients were followed longitudinally to assess SpA clinical course and longitudinal MRI sacroiliac joints, and CRP levels were reassessed 3 weeks after patients were symptom-free, following isotretinoin discontinuation.

RESULTS: Of the 513 patients, 23.98% developed IBP. MRI-proven sacroiliitis was detected in 42.3% of the symptomatic patients or 10.1% of the cohort. Among MRI-proven sacroiliitis cases, 51.9% fulfilled the Assessment of Spondyloarthritis International Society criteria for axial SpA. Mean CRP level was 32.05 ± 17.23 mg/L at pain onset and 3.4 ± 2.7 mg/L after symptom resolution. MRI findings completely resolved within 9 months (mean 6.27 ± 1.7) after isotretinoin discontinuation. MRI scores positively correlated with baseline CRP levels and global acne grading system score, pain, and the Ankylosing Spondylitis Disease Activity Score.

CONCLUSION: Isotretinoin-induced axial SpA is a prevalent side effect in acne vulgaris patients. Early detection and follow-up of isotretinoin-induced sacroiliitis can be facilitated by MRI. Cessation of isotretinoin resulted in complete resolution in all affected patients.Key Points• Detection of underdiagnosed isotretinoin side effects which are common but not always correctly diagnosed and managed.• Incidence, diagnosis, and management of these side effects in a real-world setting.• This is the first large prospective longitudinal cohort study to report on axial manifestations in patients treated with isotretinoin as well as the effect of drug cessation upon the clinical, laboratory, and radiological findings.

BACKGROUND: The SF-6D is a generic, six-dimensional health-related quality of life (HRQoL) measure derived from a selection of items from the SF-36.

OBJECTIVES: To translate, culturally adapt and validate the SF-6D for use in Arabic-speaking countries.

METHODS: The International Quality of Life Assessment (IQOLA) methodology was followed. Two forward translations, one consensus and one backward translation were undertaken. Difficulties encountered were categorized as grammatical, idiomatic, semantic/conceptual, and cultural. The content validity of the final version was tested and Cronbach's alpha test of internal consistency was used for assessing reliability. Confirmatory factor analysis (CFA), was also used to assess construct validity and to test a pre-specified relationship of observed measures.

RESULTS: Minor changes were made to the forward translation to improve cultural appropriateness. The Backward translation did not reveal major problems and equivalence to the original was confirmed following committee review. A total of 470 participants from Jordan, Egypt, UAE, Qatar and Palestine completed the translated SF-6D. All the incremental indices values are ≥0.90 and close to 1. Item loading values ranged from 0.52 to 0.87. The measurement model weight for those with chronic health conditions ranged from 0.68 to 0.91, and from 0.42 to 0.73 for those without. The percentage of variation in self-reported health state was about 55%. The measurement weight of SF-6D on self-reported health state among chronic responders was 0.87 while among responders reporting no chronic disease was 0.61. The t-value for the difference in measurement weight was -8.93 (p ≤ 0.01).

CONCLUSION: Arabic translation and cultural adaptation of SF-6D has resulted in an acceptable and culturally-adapted version that can be used in Arabic-speaking countries. Reliability and validity have been confirmed as well as ability to assess the difference in quality of life between patients with chronic health conditions and healthy individuals.

The race to find an effective treatment for coronavirus disease 2019 (COVID-19) is still on, with only two treatment options currently authorized for emergency use and/or recommended for patients hospitalized with severe respiratory symptoms: low-dose dexamethasone and remdesivir. The USA decision to stockpile the latter has resulted in widespread condemnation and in similar action being taken by some other countries. In this commentary we discuss whether stockpiling remdesivir is justified in light of the currently available evidence.

BACKGROUND: Pharmacists working in community and primary care are increasingly developing advanced skills to provide enhanced services, particularly in dealing with minor acute illness. These services can potentially free-up primary care physicians' time; however, it is not clear whether they are sufficiently cost effective to be recommended for wider provision in the UK.

OBJECTIVE: The aim of this study was to review published economic evaluations of enhanced pharmacy services in the community and primary care settings.

METHODS: We undertook a systematic review of economic evaluations of enhanced pharmacy services to inform NICE guidelines for emergency and acute care. The review protocol was developed and agreed with the guideline committee. The National Health Service Economic Evaluation Database, Health Technology Assessment Database, Health Economic Evaluations Database, MEDLINE and EMBASE were searched in December 2016 and the search was updated in March 2018. Studies were assessed for applicability and methodological quality using the NICE Economic Evaluation Checklist.

RESULTS: Of 3124 records, 13 studies published in 14 papers were included. The studies were conducted in the UK, Spain, The Netherlands, Australia, Italy and Canada. Settings included community pharmacies, primary care/general practice surgeries and patients' homes. Most of the studies were assessed as partially applicable with potentially serious limitations. Services provided in community and primary care settings were found to be either dominant or cost effective, at a £20,000 per quality-adjusted life-year threshold, compared with usual care. Those delivered in the patient's home were not found to be cost effective.

CONCLUSIONS: Advanced pharmacy services appear to be cost effective when delivered in community and primary care settings, but not in domiciliary settings. Expansion in the provision of these services in community and primary care can be recommended for wider implementation.

BACKGROUND: Pharmacists play important role in ensuring timely care delivery at the ward level. The optimal level of pharmacist input, however, is not clearly defined.

OBJECTIVE: To systematically review the evidence that assessed the outcomes of ward pharmacist input for people admitted with acute or emergent illness.

METHODS: The protocol and search strategies were developed with input from clinicians. Medline, EMBASE, Centre for Reviews and Dissemination, The Cochrane Library, NHS Economic Evaluations, Health Technology Assessment and Health Economic Evaluations databases were searched. Inclusion criteria specified the population as adults and young people (age >16 years) who are admitted to hospital with suspected or confirmed acute or emergent illness. Only randomised controlled trials (RCTs) published in English were eligible for inclusion in the effectiveness review. Economic studies were limited to full economic evaluations and comparative cost analysis. Included studies were quality-assessed. Data were extracted, summarised. and meta-analysed, where appropriate.

RESULTS: Eighteen RCTs and 7 economic studies were included. The RCTs were from USA (n = 3), Sweden (n = 2), Belgium (n = 2), China (n = 2), Australia (n = 2), Denmark (n = 2), Northern Ireland, Norway, Canada, UK and Netherlands. The economic studies were from UK (n = 2), Sweden (n = 2), Belgium and Netherlands. The results showed that regular pharmacist input was most cost effective. It reduced length-of-stay (mean = -1.74 days [95% CI: 2.76, -0.72], and increased patient and/or carer satisfaction (Relative Risk (RR) = 1.49 [1.09, 2.03] at discharge). At £20,000 per quality-adjusted life-year (QALY)-gained cost-effectiveness threshold, it was either cost-saving or cost-effective (Incremental Cost Effectiveness Ratio (ICER) = £632/QALY-gained). No evidence was found for 7-day pharmacist presence.

CONCLUSIONS: Pharmacist inclusion in the ward multidisciplinary team improves patient safety and satisfaction and is cost-effective when regularly provided throughout the ward stay. Research is needed to determine whether the provision of 7-day service is cost-effective.

Medicine price directly affects affordability and access to medicines particularly in countries where a major portion of pharmaceutical spending is through out-of-pocket payment, such as in the Asia Pacific region. We have undertaken a detailed appraisal of the pharmaceutical policy reforms to regulate drug prices in 3 developed (Australia, New Zealand, and South Korea) and 3 emerging (China, India, and Malaysia) economies of the Asia Pacific region. Despite continuous efforts by the authorities in adopting a wide range of reformatory pharmaceutical pricing policies to ensure affordability of medicines, these policies may not be optimal where drug prices were not lowered as expected (eg, in Korea). On the contrary, considerable price reductions of various pharmaceuticals have been observed in New Zealand and India because of the reform in pharmaceutical pricing policy. This review of pharmaceutical pricing reforms reinforces the need for constant monitoring by policy makers in Asia Pacific countries to regulate drug prices and to undertake reform in pharmaceutical pricing policies when necessary to ensure affordability and access to medicines.

OBJECTIVES: To assess the efficacy and safety of venous thromboembolism prophylaxis in people undergoing elective total hip replacement.

METHODS: Systematic review and Bayesian network meta-analyses of randomized controlled trials were conducted for 3 outcomes: deep vein thrombosis (DVT), pulmonary embolism (PE), and major bleeding (MB). MEDLINE, EMBASE, and Cochrane Library (CENTRAL) databases were searched. Study quality was assessed using the Cochrane risk-of-bias checklist. Fixed- and random-effects models were fitted and compared. The median relative risk (RR) and odds ratio (OR) compared with no prophylaxis, with their 95% credible intervals (CrIs), rank, and probability of being the best, were calculated.

RESULTS: Forty-two (n = 24 374, 26 interventions), 30 (n = 28 842, 23 interventions), and 24 (n = 31 792, 15 interventions) randomized controlled trials were included in the DVT, PE, and MB networks, respectively. Rivaroxaban had the highest probability of being the most effective intervention for DVT (RR 0.06 [95% CrI 0.01-0.29]). Strategy of low-molecular-weight heparin followed by aspirin had the highest probability of reducing the risk of PE and MB (RR 0.0011 [95% CrI 0.00-0.096] and OR 0.37 [95% CrI 0.00-26.96], respectively). The ranking of efficacy estimates across the 3 networks, particularly PE and MB, had very wide CrIs, indicating high degree of uncertainty.

CONCLUSIONS: A strategy of low-molecular-weight heparin given for 10 days followed by aspirin for 28 days had the best benefit-risk balance, with the highest probability of being the best on the basis of the results of the PE and MB network meta-analyses. Nevertheless, there is considerable uncertainty around the median ranks of the interventions.

BACKGROUND: Hospital-associated venous thromboembolism is a major patient safety concern. Provision of prophylaxis to patients admitted for elective total knee replacement surgery has been proposed as an effective strategy to reduce the incidence of venous thromboembolism. We aimed to assess the relative efficacy and safety of all available prophylaxis strategies in this setting.

METHODS: We did a systematic review and Bayesian network meta-analyses of randomised controlled trials to assess the relative efficacy and safety of venous thromboembolism prophylaxis strategies and to populate an economic model that assessed the cost-effectiveness of these strategies and informed the updated National Institute for Health and Care Excellence (NICE) guideline recommendations for patients undergoing elective total knee replacement surgery. The Cochrane Library (CENTRAL), Embase, and Medline were last searched on June 19, 2017, with key terms relating to the population (venous thromboembolism and total knee replacement) and the interventions compared, including available pharmacological and mechanical interventions. Outcomes of interest were deep vein thrombosis (symptomatic and asymptomatic), pulmonary embolism, and major bleeding. Risk of bias was assessed, and relevant data extracted from the included randomised controlled trials for the network meta-analyses. Relative risks (RR; with 95% credible intervals [95% CrI]) compared to no prophylaxis, median ranks (with 95% CrI), and the probability of being the best intervention were calculated. The study was done in accordance with PRISMA guidelines.

FINDINGS: 25 randomised controlled trials were included in the network meta-analyses. 23 trials (19 interventions; n=15 028) were included in the deep vein thrombosis network, 12 in the pulmonary embolism network (13 interventions; n=15 555), and 19 in the major bleeding network (11 interventions; n=19 797). Risk of bias ranged from very low to high. Rivaroxaban ranked first for prevention of deep vein thrombosis (RR 0·12 [95% CrI 0·06-0·22]). Low molecular weight heparin (LMWH; standard prophylactic dose, 28-35 days) ranked first in the pulmonary embolism network (RR 0·02 [95% CrI 0·00-3·86]) and LMWH (low prophylactic dose, 10-14 days) ranked first in the major bleeding network (odds ratio 0·08 [95% CrI 0·00-1·76]), but the results for pulmonary embolism and major bleeding are highly uncertain.

INTERPRETATION: Single prophylaxis strategies are more effective in prevention of deep vein thrombosis in the elective total knee replacement population than combination strategies, with rivaroxaban being the most effective. The results of the pulmonary embolism and major bleeding meta-analyses are uncertain and no clear conclusion can be made other than what is biologically plausible (eg, that no prophylaxis and mechanical prophylaxis strategies should have the lowest risk of major bleeding).

FUNDING: National Institute for Health and Care Excellence.

BACKGROUND: Clinical trials report severe hypoglycaemic events as the number of patients with at least one event out of the total randomised or number of events for a given total exposure. Different network meta-analysis models have been used to analyse these different data types.

OBJECTIVE: This aim of this article was to establish the impact of using the different models on effectiveness, costs and health utility estimates.

METHODS: We analysed a dataset used in a recent network meta-analysis of severe hypoglycaemic events conducted to inform National Institute for Health and Care Excellence recommendations regarding basal insulin choice for patients with type 1 diabetes mellitus. We fitted a model with a binomial likelihood reporting odds ratios (using a logit link) or hazard ratios (complementary log-log link), a model with a Poisson likelihood reporting hazard ratios and a shared-parameter model combining different types of data. We compared the results in terms of relative effects and resulting cost and disutility estimates.

RESULTS: Relative treatment effects are similar regardless of which model or scale is used. Differences were seen in the probability of having an event on the baseline treatment with the logit model giving a baseline probability of 0.07, the complementary log-log 0.17 and the Poisson 0.29. These translate into differences of up to £110 in the yearly cost of a hypoglycaemic event and 0.004 in disutility.

CONCLUSION: While choice of network meta-analysis model does not have a meaningful impact on relative effects for this outcome, care should be taken to ensure that the baseline probabilities used in an economic model are accurate to avoid misrepresenting costs and effects.

OBJECTIVE: To assess the relative efficacy and safety of basal insulin regimens in adults with type 1 diabetes mellitus (T1DM).

METHODS: A systematic review and Bayesian network meta-analysis (NMA) of randomized controlled trials comparing two or more basal insulin regimens were conducted. The following basal insulin regimens were included: Neutral Protamine Hagedorn (iNPH) (once [od], twice [bid], and four times daily [qid]), insulin detemir (iDet) (od and bid), insulin glargine 100 IU (iGlarg) (od), and insulin degludec (iDegl) (od). We searched the following databases: MEDLINE via OVID, Embase via OVID, and the Cochrane Library (Wiley). Study quality was appraised using Cochrane risk-of-bias checklist for randomized controlled trials. Two outcomes (change in hemoglobin A [HbA] and rate of severe/major hypoglycemia [SH]) were analyzed. Network inconsistency was assessed using Bucher and chi-square tests.

RESULTS: Thirty studies met the eligibility criteria. Twenty-five were included in the HbA network and 16 in the SH network. All studies were of moderate quality. No network inconsistency was evident in the HbA network. Of the seven regimens of interest, iDet (bid) had the highest probability of being best (mean change in HbA -0.48; 95% credible interval -0.69 to -0.29). In contrast, the SH network demonstrated both considerable uncertainty and significant network inconsistency (χ test, P = 0.003).

CONCLUSIONS: Of the specified frequency regimens, iDet (bid) had the highest probability of being the best basal insulin regimen in terms of reduction in HbA. Ranking of the regimens in terms of the SH rate was highly uncertain and no clear conclusion could be made.

Major orthopedic surgery, such as elective total hip replacement (eTHR) and elective total knee replacement (eTKR), are associated with a higher risk of venous thromboembolism (VTE) than other surgical procedures. Little is known, however, about the cost-effectiveness of VTE prophylaxis strategies in people undergoing these procedures. The aim of this work was to assess the cost-effectiveness of these strategies from the English National Health Service perspective to inform NICE guideline (NG89) recommendations. Cost-utility analysis, using decision modeling, was undertaken to compare 15 VTE prophylaxis strategies for eTHR and 12 for eTKR, in addition to "no prophylaxis" strategy. The analysis complied with the NICE Reference Case. Structure and assumptions were agreed with the guideline committee. Incremental net monetary benefit (INMB) was calculated, vs. the model comparator (LMWH+ antiembolism stockings), at a threshold of £20,000/quality-adjusted life-year (QALY) gained. The model was run probabilistically. Deterministic sensitivity analyses (SAs) were undertaken to assess the robustness of the results. The most cost-effective strategies were LMWH for 10 days followed by aspirin for 28 days (INMB = £530 [95% CI: -£784 to £1,103], probability of being most cost-effective = 72%) for eTHR, and foot pump (INMB = £353 [95% CI: -£101 to £665]; probability of being most cost-effective = 18%) for eTKR. There was considerable uncertainty regarding the cost-effectiveness ranking in the eTKR analysis. The results were robust to change in all SAs. For eTHR, LMWH (standard dose) for 10 days followed by aspirin for 28 days is the most cost-effective VTE prophylaxis strategy. For eTKR, the results are highly uncertain but foot pump appeared to be the most cost-effective strategy, followed closely by aspirin (low dose). Future research should focus on assessing cost-effectiveness of VTE prophylaxis in the eTKR population.