Pattern of Clinical Progression Until Metastatic Castration-Resistant Prostate Cancer: An Epidemiological Study from the European Prostate Cancer Registry.

BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed cancer in men in Europe. The impact of PCa natural history and therapeutic management on the outcomes of castration-resistant prostate cancer patients with metastasis (mCRPC) remains unclear. OBJECTIVE: The objective of this study was to describe retrospectively patterns of clinical progression through diagnosis sequences before the mCRPC stage and to assess how these sequences impacted patients' disease progression and overall survival at mCRPC stage. PATIENTS AND METHODS: Patients with mCRPC were identified from the Prostate Cancer Registry (PCR), an observational study in a real-world setting in 16 countries between 2013 and 2016. Patients were grouped in diagnosis sequences before mCRPC and defined by date of PCa diagnosis, first metastasis, and castration resistance. Distribution of time-to-event variables were estimated using Kaplan-Meier product-limit survival curves for overall survival (OS) and progression-free survival (PFS). Non-adjusted Cox models were conducted for efficacy endpoints (OS, PFS) to estimate hazard ratios between diagnosis sequences. RESULTS: At the end of study, 2859 mCRPC patients were included in this analysis. Among mCRPC four diagnosis sequences were identified: 35% developed metastases (mHSPC) before becoming castration resistant (sequence 1, metachronous mHSPC), 10% developed castration resistance (nmCRPC) before metastases (sequence 2), 27% developed metastases and castration resistance within 4 months (sequence 3) and 28% of patients were de novo mHSPC (sequence 4). Median OS was 17.7 months (interquartile range (IQR): 8.8-29.9) and PFS was 6.4 months (IQR: 3.2-12.0). The univariate analyses showed no correlation between mCRPC patients' OS or PFS and the diagnosis sequence. CONCLUSION: This large European study describe four different patterns of prostate cancer progression to mCRPC stage. Our results indicate that patient survival becomes comparable after progression to mCRPC, regardless of the diagnosis sequence. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02236637; registered September 2014.

Author Correction: A stochastic agent-based model of the SARS-CoV-2 epidemic in France.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A stochastic agent-based model of the SARS-CoV-2 epidemic in France.

Many European countries have responded to the COVID-19 pandemic by implementing nationwide protection measures and lockdowns1. However, the epidemic could rebound when such measures are relaxed, possibly leading to a requirement for a second or more, repeated lockdowns2. Here, we present results of a stochastic agent-based microsimulation model of the COVID-19 epidemic in France. We examined the potential impact of post-lockdown measures, including physical distancing, mask-wearing and shielding individuals who are the most vulnerable to severe COVID-19 infection, on cumulative disease incidence and mortality, and on intensive care unit (ICU)-bed occupancy. While lockdown is effective in containing the viral spread, once lifted, regardless of duration, it would be unlikely to prevent a rebound. Both physical distancing and mask-wearing, although effective in slowing the epidemic and in reducing mortality, would also be ineffective in ultimately preventing ICUs from becoming overwhelmed and a subsequent second lockdown. However, these measures coupled with the shielding of vulnerable people would be associated with better outcomes, including lower mortality and maintaining an adequate ICU capacity to prevent a second lockdown. Benefits would nonetheless be markedly reduced if most people do not adhere to these measures, or if they are not maintained for a sufficiently long period.

Facing the COVID-19 epidemic in NYC: a stochastic agent-based model of various intervention strategies.

Global spread of coronavirus disease 2019 (COVID-19) has created an unprecedented infectious disease crisis worldwide. Despite uncertainties about COVID-19, model-based forecasting of competing mitigation measures on its course is urgently needed to inform mitigation policy. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in New York City and evaluated the potential impact of quarantine duration (from 4 to 16 weeks), quarantine lifting type (1-step lifting for all individuals versus a 2-step lifting according to age), post-quarantine screening, and use of a hypothetical effective treatment against COVID-19 on the disease's cumulative incidence and mortality, and on ICU-bed occupancy. The source code of the model has been deposited in a public source code repository (GitHub®). The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is efficient to contain the viral spread, it is unlikely to prevent a rebound of the epidemic once lifted. We projected that lifting quarantine in a single step for the full population would be unlikely to substantially lower the cumulative mortality, regardless of quarantine duration. By contrast, a two-step quarantine lifting according to age was associated with a substantially lower cumulative mortality and incidence, up to 71% and 23%, respectively, as well as lower ICU-bed occupancy. Although post-quarantine screening was associated with diminished epidemic rebound, this strategy may not prevent ICUs from being overcrowded. It may even become deleterious after a 2-step quarantine lifting according to age if the herd immunity effect does not had sufficient time to become established in the younger population when the quarantine is lifted for the older population. An effective treatment against COVID-19 would considerably reduce the consequences of the epidemic, even more so if ICU capacity is not exceeded.

Lockdown exit strategies and risk of a second epidemic peak: a stochastic agent-based model of SARS-CoV-2 epidemic in France.

Most European countries have responded to the COVID-19 threat by nationwide implementation of barrier measures and lockdown. However, assuming that population immunity will build up through the epidemic, it is likely to rebound once these measures are relaxed, possibly leading to a second or multiple repeated lockdowns. In this report, we present results of epidemiological modelling that has helped inform policy making in France. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in France, and examined the potential impact of post-quarantine measures, including social distancing, mask-wearing, and shielding of the population the most vulnerable to severe COVID-19 infection, on the disease's cumulative incidence and mortality, and on ICU-bed occupancy. The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is effective in containing the viral spread, it would be unlikely to prevent a rebound of the epidemic once lifted, regardless of its duration. Both social distancing and mask-wearing, although effective in slowing the epidemic and in reducing mortality, would also be ineffective in ultimately preventing the overwhelming of ICUs and a second lockdown. However, these measures coupled with shielding of vulnerable people would be associated with better outcomes, including lower cumulative incidence, mortality, and maintaining an adequate number of ICU beds to prevent a second lockdown. Benefits would nonetheless be markedly reduced if these measures were not applied by most people or not maintained for a sufficiently long period, as herd immunity progressively establishes in the less vulnerable population.

Organised screening for cervical cancer in France: a cost-effectiveness assessment.

OBJECTIVE: According to the third cancer plan, organised screening (OS) of cervical cancer (CC) among women aged 25-65 years should be implemented in France in the forthcoming years. The most efficient way to implement OS in the French healthcare system is yet to be determined. METHODS: A microsimulation model was developed adopting a collective 'all payers' perspective. A closed cohort of women eligible for CC screening and representative in terms of age and participation in individual screening (IndScr) by annual Papanicolaou (Pap) testing every 3 years was modelled on a lifetime horizon. Different OS strategies, additive to IndScr with a 61.9% participation rate based on mailed invitations to non-participant women to perform OS were assessed. Similar modalities were applied to OS and IndScr participants. Strategies implied different screening tests (Papanicolaou (Pap) test, human papillomavirus (HPV) test and p16/Ki67 double staining) and OS periodicity. RESULTS: Compared with IndScr only, all OS strategies were associated with decreased cancer incidence/mortality (from 14.2%/13.5% to 22.9%/25.8%). Most strategies generated extra costs ranging from €37.9 to €1607 per eligible woman. HPV testing every 10 and 5 years were cost saving. HPV tests every 10 and 5 years were the most efficient strategies, generating more survival at lower costs than Pap-based strategies. Compared to IndScr only, an HPV test every 10 years was cost saving. The most effective strategies were p16/Ki67 as primary or HPV positive confirmation tests, with respective incremental cost-effectiveness ratios of €6 541 250 and €101 391 per life year. Pap-based strategies generated intermediary results. CONCLUSION: OS strategies based on the HPV test appear highly efficient. However, our results rely on the assumption that women and practitioners comply with the recommended OS periodicities (3, 5, 10 years). Implementing these OS modalities will require major adaptations to the current CC screening organisation. Pap test-based strategies might be simpler to setup while preparing an appropriate implementation of more efficient OS screening modalities.

A comparison of HAS & NICE guidelines for the economic evaluation of health technologies in the context of their respective national health care systems and cultural environments.

BACKGROUND: Health technology assessment (HTA) has been reinforced in France, notably with the introduction of economic evaluation in the pricing process for the most innovative and expensive treatments. Similarly to the National Institute for Clinical Excellence (NICE) in England, the National Authority for Health (HAS), which is responsible for economic evaluation of new health technologies in France, has published recommendations on the methods of economic evaluation. Since economic assessment represents a major element of HTA in England, exploring the differences between these methodological guidelines might help to comprehend both the shape and the role economic assessment is intended to have in the French health care system. METHODS: Methodological guidelines for economic evaluation in France and England have been compared topic-by-topic in order to bring out key differences in the recommended methods for economic evaluation. RESULTS: The analysis of both guidelines has revealed multiple similarities between France and England, although a number of differences were also noted regarding the elected methodology of analysis, the comparison of studies' outcomes with cost-effectiveness thresholds, the study population to consider, the quality of life valuation methods, the perspective on costs, the types of resources considered and their valuation, the discount rates to apply in order to reflect the present value of interventions, etc. To account for these differences, modifications will be required in order to adapt economic models from one country to the other. CONCLUSIONS: Changes in HTA assessment methods occur in response to different challenges determined by the different philosophical and cultural considerations surrounding health and welfare as well as the political considerations regarding the role of public policies and the importance of their evaluation.