Real-world data and evidence in health technology assessment: When are they complementary, substitutes, or the only sources of data compared to clinical trials?

Within the life-cycle assessment of health technologies, real-world data (RWD) have until now been of secondary importance to clinical trial data. The availability of massive, better quality RWD, particularly with the emergence of connected devices, the improvement of methods for characterizing populations, make it possible to have a better insight into the effects of treatment, sometimes on a national scale the importance of RWD is likely to progress in the eyes of health technology assessors, going from being traditionally complementary to possibly replacing clinical trial data. This is the fundamental question that the round table, involving experts from the academic and/or hospital, institutional, and industrial worlds, set out to answer. This work served first to establish the current role of RWD in health technology assessment, by distinguishing the main purposes of RWD, the timing of the evaluation in relation to the life cycle of the technology, and then according to the party commissioning or receiving the outcomes of RWD-based studies. Secondly, the round table proposed six general recommendations for more intensive and decisive use of RWD in the assessment and decision-making process.

Costs and mortality associated with HIV: a machine learning analysis of the French national health insurance database.

BACKGROUND: The objective is to characterise the economic burden to the healthcare system of people living with HIV (PLWHIV) in France and to help decision makers in identifying risk factors associated with high-cost and high mortality profiles. DESIGN AND METHODS: The study is a retrospective analysis of PLWHIV identified in the French National Health Insurance database (SNDS). All PLWHIV present in the database in 2013 were identified.  All healthcare resource consumption from 2008 to 2015 inclusive was documented and costed (for 2013 to 2015) from the perspective of public health insurance. High-cost and high mortality patient profiles were identified by a machine learning algorithm. RESULTS: In 2013, 96,423 PLWHIV were identified in the SNDS database, including 3,373 incident cases. Overall, 3,224 PLWHIV died during the three-year follow-up period (mean annual mortality rate: 1.1%). The mean annual per capita cost incurred by PLWHIV was € 14,223, corresponding to a total management cost of HIV of € 1,370 million in 2013. The largest contribution came from the cost of antiretroviral medication (M€ 870; 63%) followed by hospitalisation (M€ 154; 11%). The costs incurred in the year preceding death were considerably higher. Four specific patient profiles were identified for under/over-expressing these costs, suggesting ways to reduce them. CONCLUSIONS: Even though current therapeutic regimens provide excellent virological control in most patients, PLWHIV have excess mortality. Other factors such as comorbidities, lifestyle factors and screening for cancer and cardiovascular disease, need to be targeted in order to lower the mortality and cost associated with HIV infection.

Hospital burden of pulmonary arterial hypertension in France.

BACKGROUND & AIMS: Pulmonary arterial hypertension is a severe disease associated with frequent hospitalisations. This retrospective analysis of the French medical information PMSI-MSO database aimed to describe incident cases of patients with pulmonary arterial hypertension hospitalised in France in 2013 and to document associated hospitalisation costs from the national health insurance perspective. METHODS: Cases of pulmonary arterial hypertension were identified using a diagnostic algorithm. All cases hospitalised in 2013 with no hospitalisation the previous two years were retained. All hospital stays during the year following the index hospitalisation were extracted, and classified as incident stays, monitoring stays or stays due to disease worsening. Costs were attributed from French national tariffs. RESULTS: 384 patients in France were hospitalised with incident pulmonary arterial hypertension in 2013. Over the following twelve months, patients made 1,271 stays related to pulmonary arterial hypertension (415 incident stays, 604 monitoring stays and 252 worsening stays). Mean age was 59.6 years and 241 (62.8%) patients were women. Liver disease and connective tissue diseases were documented in 62 patients (16.1%) each. Thirty-one patients (8.1%) died during hospitalisation and four (1.0%) received a lung/heart-lung transplantation. The total annual cost of these hospitalisations was € 3,640,382. € 2,985,936 was attributable to standard tariffs (82.0%), € 463,325 to additional ICU stays (12.7%) and € 191,118 to expensive drugs (5.2%). The mean cost/stay was € 2,864, ranging from € 1,282 for monitoring stays to € 7,285 for worsening stays. CONCLUSIONS: Although pulmonary arterial hypertension is rare, it carries a high economic burden.

Pacemaker complications and costs: a nationwide economic study.

Aims: Novel leadless pacemakers (LPMs) may reduce complications and associated costs related to conventional pacemaker systems. This study sought to estimate the incidence and associated costs of traditional pacemaker complications, in those patients who were eligible for LPM implantation. Methods: A retrospective analysis was conducted on the French National Hospital Database (PMSI), including all patients implanted with a pacemaker in France in 2012, who could have alternatively received an LPM. Complication rates and their associated costs 3 years post-implantation were estimated from the perspective of the French social security system. Results: From a total of 65,553 patients, 11,770 (18%) met the inclusion criteria. Overall, 618 patients (5.3%) had a record of pacemaker complications during follow-up, of which 89% were related to the lead and pocket. Most common were pocket bleeding, lead- or generator-related mechanical complications, and pneumothorax. Overall, the mean cost of pacemaker complications per patient was €6,674 ± 3,867 at 3 years. Specifically, €7,143 ± 2,685 for pocket bleeding, €5,123 ± 2,676 for pneumothorax, and €6,020 ± 3,272 for mechanical complications. Conclusions: Major complications associated with the lead and pocket of conventional pacemaker systems are still common, and these represent a significant burden to healthcare systems as they generate substantial costs.

The surgical treatment of idiopathic abnormal uterine bleeding: An analysis of 88 000 patients from the French exhaustive national hospital discharge database from 2009 to 2015.

OBJECTIVE: The objective of the study was to compare success rates, complications and management costs of different surgical techniques for abnormal uterine bleeding (AUB). METHODS: This was a retrospective analysis of the French national hospital discharge database. All hospital stays with a diagnostic code for AUB and an appropriate surgical procedure code between 2009 and 2015 inclusive were identified, concerning 109,884 women overall. Outcomes were compared between second generation procedures (2G surgery), first-generation procedures (1G surgery), curettage and hysterectomy. Clinical outcomes were treatment failure and complications during the follow-up period. Costs were attributed using standard French hospital tariffs. RESULTS: 7,863 women underwent a 2G procedure (7.2%), 39,935 a 1G procedure, (36.3%), 38,923 curettage (35.4%) and 23,163 hysterectomy (21.1%). Failure rates at 18 months were 9.9% for 2G surgery, 12.7% for 1G surgery, 20.6% for curettage and 2.8% for hysterectomy. Complication rates at 18 months were 1.9% for 2G surgery, 1.5% for 1G surgery, 1.4% for curettage and 5.3% for hysterectomy. Median 18-month costs were € 1 173 for 2G surgery, € 1 059 for 1G surgery, € 782 for curettage and € 3 090 for hysterectomy. CONCLUSION: Curettage has the highest failure rate. Hysterectomy has the lowest failure rate but the highest complication rate and is also the most expensive. Despite good clinical outcomes and relatively low cost, 1G and 2G procedures are not widely used. Current guidelines for treatment of AUB are not respected, the recommended 2G procedures being only used in <10% of cases.

Hospital costs impact of post ischemic stroke dysphagia: Database analyses of hospital discharges in France and Switzerland.

INTRODUCTION: Oropharyngeal dysphagia is frequent in hospitalized post-stroke patients and is associated with increased mortality and comorbidities. The aim of our analysis was to evaluate the impact of dysphagia on Length of Hospital Stay (LOS) and costs. The hospital perspective was used to assess costs. METHODS: Hospital discharge databases comparing hospital stays for ischemic stroke associated with dysphagia vs stroke without dysphagia in France and Switzerland were analyzed. The French Medical Information System Program (PMSI) database analysis focused on 62'297 stays for stroke in the public sector. 6'037 hospital stays for stroke were analyzed from the Swiss OFS (Office fédéral de la statistique: Statistique des coûts par cas 2012) database. Diagnosis codes and listing of procedures were used to identify dysphagia in stroke patients. RESULTS: Patients with post-stroke dysphagia accounted for 8.4% of stroke hospital stays in Switzerland, which is consistent with recently reported prevalence of dysphagia at hospital discharge (Arnold et al, 2016). The French database analysis identified 4.2% stays with post-stroke dysphagia. We hypothesize that the difference between the Swiss and French datasets may be explained by the limitations of an analysis based on diagnosis and procedure coding. Patients with post-stroke dysphagia stayed longer at hospitals (LOS of 23.7 vs. 11.8 days in France and LOS of 14.9 vs. 8.9 days in Switzerland) compared with patients without post-stroke dysphagia. Post-stroke dysphagia was associated with about €3'000 and CHF14'000 cost increase in France and Switzerland respectively. DISCUSSION: In this study post-stroke dysphagia was associated with increased LOS and higher hospital costs. It is difficult to isolate the impact of dysphagia in patients with multiple symptoms and disabilities impacting rehabilitation and recovery. After adjusting for confounding factors by matching stays according to age, sex and stroke complications, post-stroke dysphagia association with increased LOS and higher hospital costs was found to be independent of sensory or motor complications. CONCLUSION: Post-stroke dysphagia is associated with increased length of hospital stay and higher hospital costs.

Extra cost of brain metastases (BM) in patients with non-squamous non-small cell lung cancer (NSCLC): a French national hospital database analysis.

PURPOSE: To assess the incremental cost associated with the management of patients with primary non-squamous non-small cell lung cancer (NSCLC) with brain metastases at the time of diagnosis. METHODS: Data were extracted from the French Hospital medical information database (Programme de Médicalisation des Systèmes d'Information (PMSI)). Patients with non-squamous NSCLC were identified through a diagnosis of lung cancer and a prescription of bevacizumab or pemetrexed. All such patients hospitalised with lung cancer for the first time in 2013 and with metastases identified at the first hospitalisation were eligible. Two cohorts were identified, one with brain metastases (group B: n=971) and one with metastases at other sites (group A: n=1529). For each patient, total in-hospital medical resource consumption associated with the initial hospitalisation in 2013 and with any follow-up stays in the following 24 months was documented. Costs were attributed from official French national tariffs and expressed in 2017 euros. RESULTS: The mean number of hospitalisations per patient in the 24-moth follow-up period was 17 in group A and 21 in group B. >99% of patients in both groups received chemotherapy. 58% of patients in group B and 13% in group A were managed by radiotherapy. 37% in group B and 24% in group A received palliative care. The associated cost was €2979 per patient-month for patients in group B and €2426 for patients in group A, representing a differential cost of €553 per month. Radiotherapy (+€164/month) and palliative care (+€130/month) were the principal drivers of the incremental cost. CONCLUSIONS: The presence of brain metastases at the time of diagnosis of non-squamous NSCLC carries a significant burden, and ways of lowering this burden are needed.

Costs associated with hospitalization in HIV-positive patients in France.

OBJECTIVES: To estimate the number of patients hospitalized for HIV-related reasons in France, to describe their characteristics and to estimate hospitalization-associated costs. DESIGN: A retrospective analysis of the French hospital medical information database (Programme de médicalisation des systèmes d'information en médecine, chirurgie, obstétrique et odontologie database). METHODS: Patients hospitalized with HIV in France in 2013 and 2014 were identified in the database through International Classification of Diseases, 10th revision diagnostic codes as well as comorbidities and opportunistic infections. Hospital stays for each patient were extracted over a 12-month period following the initial index hospitalization. Costing was performed from the perspective of national health insurance. Direct costs were attributed from national tariffs for medical acts and expressed in 2016 Euros. RESULTS: During the study period, 70 180 stays, including day (80%) and overnight (20%) hospitalization, of patients with HIV were identified, of which 37 477 stays (by 20 126 patients) were directly related to HIV. In patients with overnight hospitalization, an opportunistic infection was documented in 50% of patients and at least one comorbidity were identified in 85% of patients. The overall estimated total annual cost of hospital stays was &OV0556; 64 126 616 (median annual cost per patient: &OV0556; 545). The median annual per capita cost was &OV0556; 541 for day hospitalization, &OV0556; 7664 for overnight stay with comorbidities and &OV0556; 9059 for overnight stay with opportunistic infections. CONCLUSION: Most patients hospitalized with HIV in France presented an opportunistic infection or at least one comorbidity that contributed to costs of hospitalization. The organization of interfaces between different healthcare providers in hospital and community practice needs to be organized so that comorbidities are identified and managed optimally.

Hospitalisation costs of metastatic melanoma in France; the MELISSA study (MELanoma In hoSpital coSts Assessment).

BACKGROUND: Management of metastatic melanoma is changing rapidly following the introduction of innovative effective therapies, with consequences for the allocation of healthcare resources. The objective of this study was to assess hospitalisation costs of metastatic melanoma in France from 2011 to 2013 from the perspective of the government payer. METHODS: The population studied corresponded to all adults with metastatic melanoma hospitalised in France between 1st January 2011 and 31st December 2013 who required chemotherapy, immunotherapy or radiotherapy due to tumour progression and unresectable Stage III or Stage IV melanoma. Metastatic melanoma was identified by ICD-10 codes documented in the hospital patient discharge records. For each patient, hospital stays were stratified into a pre- or post- progression health state using proxy variables for the RECIST criteria. All healthcare expenditure documented in the French national hospital claims system database and incurred between the index hospitalisation (or change of progression state) and the end of follow-up were analysed. For the principal analysis, valuation of healthcare resource consumption was performed using official national hospitalisation tariffs. Any expensive therapy administered during the stay was documented from a linked database of expensive drugs (FICHCOMP). RESULTS: Seventy-eight thousand seven hundred fifty hospital stays by 10,337 patients with metastatic melanoma were identified over the three-year study period. Annual per capita costs of hospitalisation were € 5046 in the pre-progression stage and € 19,006 in the post-progression stage. Hospitalisations attributed to adverse drug reactions to chemotherapy or immunotherapy were observed in 27% of patients. Annual per capita costs of these hospitalisations related to adverse drug reactions were € 3762 in the pre-progression stage and € 5523 in the post-progression stage. CONCLUSIONS: Hospitalisation costs related to metastatic melanoma rise substantially as the disease progresses. Treatment strategies which slow down disease progression would be expected to reduce costs of hospitalisation for metastatic melanoma, although they may also entail significant acquisition costs. This will entail organisational changes of resource allocation for the treatment of metastatic melanoma in hospitals.

[Regional differences in hospitalisations for complications of chronic hepatitis C in 2012]. / Disparités régionales des hospitalisations pour complication de l'hépatite chronique C en 2012.

Objective: Only limited recent information is available concerning the regional incidence and prevalence of chronic hepatitis C (CHC), but this information is critical for optimal definition of public health policies for the management of hepatitis C. The objective of this study was to evaluate the feasibility of mapping potential regional differences in the prevalence of CHC and its complications using data from a health administrative database. Methods: The 2012 PMSI MCO hospital database contains information on diagnosis and healthcare resource use, essentially related to all hospitalisations in France. Hospital stays related to CHC were identified on the basis of ICD-10 disease codes. Hospital stays were classified according to stage of liver disease: non-cirrhotic liver disease, compensated cirrhosis, decompensated cirrhosis or hepatocellular carcinoma (HCC). All study variables were documented for each French administrative region in 2012. Results: In 2012, 12,040 patients were hospitalised in France for a reason related to CHC, corresponding to a standardised age- and gender- adjusted prevalence rate of 19.3/100,000 persons. The highest prevalences of CHC and HCC were observed in the Ile de France, Alsace and Provence-Alpes-Côte-d'Azur regions. Conclusions: This study demonstrates the feasibility of using the PMSI database to identify regional differences in the prevalence of CHC. This information may be useful for planning regional healthcare resource provision for CHC.

Chronic hepatitis C: Burden of disease and cost associated with hospitalisations in France in 2012 (The HEPC-LONE study).

BACKGROUND AND OBJECTIVE: This retrospective hospital database analysis aimed to determine the burden and cost of hospitalisations related to chronic hepatitis C (CHC) infections in France in 2012. METHODS: All hospital stays with CHC (ICD-10 code B18.2) coded as the principal, related or significantly associated diagnosis were extracted from the French National Hospital database 2012 (PMSI). Hospitalisations not directly related to CHC were excluded. Patients were assigned to a liver disease stage, namely non-cirrhotic liver disease, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma or post-liver transplantation. Costing was performed using French national tariffs and expressed in 2013 Euros. We documented 22,056 hospital stays involving 12,040 patients who were considered to be directly related to CHC. Of these stays, 11,779 (53.4%) were documented in patients with severe complications (decompensated cirrhosis, hepatocellular carcinoma or liver transplantation). RESULTS AND CONCLUSIONS: The mean number and duration of hospital stays increased with disease severity. Overall, 1181 patients (9.8%) died during hospitalisation. The total cost of hospital stays for CHC was estimated to be € 61 million, of which 26.4% were attributable to hepatocellular carcinoma, 32.5% to post-liver transplantation and 21.0% to decompensated cirrhosis. Compared with a previous analysis in 2009, the number of patients hospitalised fell by 22%, although the patients hospitalised were overall more severely ill. The total cost of hospitalisation decreased by 8%, with a notably marked reduction in the number of biopsies performed (32%). This study illustrates the persistently high burden of CHC infections in France.