BackgroundIn the UK, women are invited for 3-yearly mammography screening, through the NHS Breast Screening Programme (NHSBSP), from the ages of 47–50 years to the ages of 69–73 years. Women with family histories of breast cancer can, from the age of 40 years, obtain enhanced surveillance and, in exceptionally high-risk cases, magnetic resonance imaging. However, no NHSBSP risk assessment is undertaken. Risk prediction models are able to categorise women by risk using known risk factors, although accurate individual risk prediction remains elusive. The identification of mammographic breast density (MD) and common genetic risk variants [single nucleotide polymorphisms (SNPs)] has presaged the improved precision of risk models.ObjectivesTo (1) identify the best performing model to assess breast cancer risk in family history clinic (FHC) and population settings; (2) use information from MD/SNPs to improve risk prediction; (3) assess the acceptability and feasibility of offering risk assessment in the NHSBSP; and (4) identify the incremental costs and benefits of risk stratified screening in a preliminary cost-effectiveness analysis.DesignTwo cohort studies assessing breast cancer incidence.SettingHigh-risk FHC and the NHSBSP Greater Manchester, UK.ParticipantsA total of 10,000 women aged 20–79 years [Family History Risk Study (FH-Risk); UK Clinical Research Network identification number (UKCRN-ID) 8611] and 53,000 women from the NHSBSP [aged 46–73 years; Predicting the Risk of Cancer At Screening (PROCAS) study; UKCRN-ID 8080].InterventionsQuestionnaires collected standard risk information, and mammograms were assessed for breast density by a number of techniques. All FH-Risk and 10,000 PROCAS participants participated in deoxyribonucleic acid (DNA) studies. The risk prediction models Manual method, Tyrer–Cuzick (TC), BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) and Gail were used to assess risk, with modelling based on MD and SNPs. A preliminary model-based cost-effectiveness analysis of risk stratified screening was conducted.Main outcome measuresBreast cancer incidence.Data sourcesThe NHSBSP; cancer registration.ResultsA total of 446 women developed incident breast cancers in FH-Risk in 97,958 years of follow-up. All risk models accurately stratified women into risk categories. TC had better risk precision than Gail, and BOADICEA accurately predicted risk in the 6268 single probands. The Manual model was also accurate in the whole cohort. In PROCAS, TC had better risk precision than Gail [area under the curve (AUC) 0.58 vs. 0.54], identifying 547 prospective breast cancers. The addition of SNPs in the FH-Risk case–control study improved risk precision but was not useful inBRCA1(breast cancer 1 gene) families. Risk modelling of SNPs in PROCAS showed an incremental improvement from using SNP18 used in PROCAS to SNP67. MD measured by visual assessment score provided better risk stratification than automatic measures, despite wide intra- and inter-reader variability. Using a MD-adjusted TC model in PROCAS improved risk stratification (AUC = 0.6) and identified significantly higher rates (4.7 per 10,000 vs. 1.3 per 10,000;p < 0.001) of high-stage cancers in women with above-average breast cancer risks. It is not possible to provide estimates of the incremental costs and benefits of risk stratified screening because of lack of data inputs for key parameters in the model-based cost-effectiveness analysis.ConclusionsRisk precision can be improved by using DNA and MD, and can potentially be used to stratify NHSBSP screening. It may also identify those at greater risk of high-stage cancers for enhanced screening. The cost-effectiveness of risk stratified screening is currently associated with extensive uncertainty. Additional research is needed to identify data needed for key inputs into model-based cost-effectiveness analyses to identify the impact on health-care resource use and patient benefits.Future workA pilot of real-time NHSBSP risk prediction to identify women for chemoprevention and enhanced screening is required.FundingThe National Institute for Health Research Programme Grants for Applied Research programme. The DNA saliva collection for SNP analysis for PROCAS was funded by the Genesis Breast Cancer Prevention Appeal.

Introduction Combination antiretroviral therapy (cART) improves outcomes for people living with HIV (PLWH) but requires adherence to daily dosing. Suboptimal adherence results in reduced treatment effectiveness, increased costs, and greater risk of resistance and onwards transmission. Treatment with long-acting (LA), injection-based ART administered by healthcare professionals (directly observed therapy (DOT)) eliminates the need for adherence to daily dosing and may improve clinical outcomes. This study reports the cost-effectiveness of the cabotegravir plus rilpivirine LA regimen (CAB+RPV LA) and models the potential impact of LA DOT therapies. Methods Parameterisation was performed using pooled data from recent CAB+RPV LA Phase III trials. The analysis was conducted using a cohort-level hybrid decision-tree and state-transition model, with states defined by viral load and CD4 cell count. The efficacy of oral cART was adjusted to reflect adherence to daily regimens from published data. A Canadian health service perspective was adopted. Results CAB+RPV LA is predicted to be the dominant intervention when compared to oral cART, generating, per 1,000 patients treated, lifetime cost-savings of $1.5 million, QALY and life-year gains of 107 and 138 respectively with three new HIV cases averted. Conclusions Economic evaluations of LA DOTs need to account for the impact of adherence and HIV transmission. This study adds to the existing literature by incorporating transmission and using clinical data from the first LA DOT regimen. Providing PLWH and healthcare providers with novel modes of ART administration, enhancing individualisation of treatment, may facilitate the achievement of UNAIDS 95-95-95 objectives.

Background Iron deficiency anaemia (IDA) is common in inflammatory bowel disease (IBD) and can significantly impair health-related quality of life (HRQoL). IV iron is currently the main treatment for patients intolerant or unsuitable for standard oral iron. Ferric maltol (FM), a stable oral complex of ferric iron and maltol, is designed to provide efficient iron delivery and minimise formation of free iron in the gut, thus reducing the potential for gastric adverse events. The HRQoL benefits of FM and ferric carboxymaltose (FCM) and their relationship to haematological parameters were analysed using data from a randomised controlled trial. Methods Patients with IBD and IDA were randomised to FM (30 mg b.i.d) or IV FCM (as per local SmPC) in an open-label, Phase 3b non-inferiority study (primary endpoint haemoglobin [Hb] responder rate [proportion of patients with ≥2 g/dl increase or normalisation of Hb at week 12]; non-inferiority margin 20%). HRQoL was assessed via the Short Form Health Survey (SF-36). In a post-hoc analysis of patient-level data, Hb, serum iron and HRQoL at baseline and week 12 were summarised descriptively and correlations between HRQoL and haematological parameters were assessed via Pearson’s correlation coefficient (PCC). Results 250 patients were randomised: 125 to FM (per-protocol [PP] n = 86) and 125 to IV FCM (PP n = 92). FM was non-inferior to FCM on the primary endpoint (response rate 74% and 83% for FM and IV FCM respectively [PP population], risk difference -0.1 [two-sided p = 0.017; 95% CI -0.2, 0.0]). Hb, serum iron and HRQoL all improved following both treatments at Week 12. Improvements in SF-36 physical component summary (PCS) and mental component summary (MCS) scores were slightly greater with FM (difference not statistically significant; Table 1). HRQoL improved across all SF-36 domain scores with both FM and FCM, with no statistically significant differences between treatments (Figure 1). HRQoL (MCS and PCS) improvements were positively associated with increases in Hb and serum iron (Table 1). Conclusion FM provides non-inferior efficacy to IV FCM with at least as great a benefit to HRQoL and may, therefore, provide an oral alternative to IV iron in patients with IBD.

With interest and concern we read "Fluocinolone Acetonide Intravitreal Implant for Treating Recurrent Non-infectious Uveitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal" by Pouwels et al. [1], published in the November 2019 issue of Pharmacoeconomics. While we appreciate the role of the Evidence Review Group (ERG) in scrutinising the company submission and providing a different view on the evidence presented by the company, we believe there are several misunderstandings and methodological errors in the publication by Pouwels et al. [1]. Due to the necessary brevity of this letter, only the most substantial of these are addressed here.

Background Iron deficiency anaemia (IDA) is common in patients with inflammatory bowel disease (IBD) and can significantly impair health-related quality of life. IDA imposes a substantial economic burden on healthcare payers resulting primarily from increased medical costs and increased rates of hospital admission. IV iron is currently the main treatment for patients intolerant or unsuitable for standard oral iron. Ferric maltol (FM), a stable oral complex of ferric (Fe3+) iron and maltol, is designed to reduce exposure to elemental iron and thus limit gastrointestinal damage. This analysis compares the productivity loss associated with oral FM and IV ferric carboxymaltose (FCM) treatment. Methods Patients with IBD and IDA (haemoglobin [Hb] ≥8.0 g/dl and ≤11.0 g/dl for women or ≥8.0 g/dl and ≤12.0 g/dl for men, and ferritin &lt;30 ng/ml or ferritin &lt;100 ng/ml with transferrin saturation &lt;20%) were randomised to receive FM (30 mg b.i.d) or IV FCM (as per local SmPC) in an open-label, Phase 3b non-inferiority study. The primary endpoint was Hb responder rate (proportion of patients achieving a ≥2 g/dl increase or normalisation of Hb at week 12); the margin for non-inferiority was 20%. Productivity loss was calculated based on the number of days lost due to iron therapy during the initial 12-week study period. The costs associated with lost productivity were calculated using the human capital approach and based on the average gross income from Germany. Results 250 patients were randomised: 125 to FM and 125 to IV FCM. The primary non-inferiority endpoint was met. IV FCM treatment resulted in a loss of patient time because IV administration was limited to a hospital or outpatient setting: 50% of patients treated with IV FCM lost at least one full day due to treatment, with 1 in 15 losing 4–6 days (Table 1). Productivity loss was quantified, with IV FCM treatment associated with losses between €0.00 and €107.21 in 50% of patients, €129.17 and €387.51 in 43% of patients and €516.68 and €775.02 in 7% of patients. FM was administered orally by the patient and did not require any in-hospital treatment, there was no treatment linked productivity loss. Conclusion IV FCM treatment resulted in productivity loss and disruption to patients’ work and family life due to the need for in-hospital/outpatient IV administration. FM treatment had no associated productivity loss as it was administered orally by the patient. FM has none of the indirect costs associated with IV FCM administration and may provide an oral alternative to IV iron in patients with IBD.