Melanoma In France Research Articles

EE668 Cost-Effectiveness of Pembrolizumab as an Adjuvant Treatment for Adults and Adolescents Aged 12 Years and Older With Resected Stage IIB/IIC Melanoma in France

EE668 Cost-Effectiveness of Pembrolizumab as an Adjuvant Treatment for Adults and Adolescents Aged 12 Years and Older With Resected Stage IIB/IIC Melanoma in France

Epidemiology and characteristics of acral lentiginous melanoma compared to lentigo melanoma in France: a multicentric retrospective study from the French cohort RIC-Mel database

Skin phototype, latitude and sun exposure are classic risk factors for melanomas but are not relevant to acrolentiginous melanomas (ALM). ALM is not related to chronic sun exposure because the thick stratum corneum acts as a barrier to penetration of UV rays, whereas LMM occurs in skin with high photoaging due to chronic sun exposure. This study aimed to determine if any difference exists between "solar" melanomas and "non-solar" melanomas based on a comparison between LMM and ALM. We extracted all data for ALM and LMM patients, from March 2012 to September 2020, from the RIC-Mel national database to perform a descriptive cohort analysis of 1,056 Caucasian cases. The profiles of solar-related and non-solar melanoma seem to be different, and prognostic factors of ALM at diagnosis are less favourable compared to LMM, suggesting that non-solar melanoma is more aggressive than solar-related melanoma and that sentinel lymph node biopsy should be performed.

Health status of prevalent cancer cases as measured by mortality dynamics (cancer vs. noncancer): Application to five major cancers sites.

Cancer prevalence is heterogeneous because it includes individuals who are undergoing initial treatment and those who are in remission, experiencing relapse, or cured. The proposed statistical approach describes the health status of this group by estimating the probabilities of death among prevalent cases. The application concerns colorectal, lung, breast, and prostate cancers and melanoma in France in 2017. Excess mortality was used to estimate the probabilities of death from cancer and other causes. For the studied cancers, most deaths from cancer occurred during the first 5 years after diagnosis. The probability of death from cancer decreased with increasing time since diagnosis except for breast cancer, for which it remained relatively stable. The time beyond which the probability of death from cancer became lower than that from other causes depended on age and cancer site: for colorectal cancer, it was 6 years after diagnosis for women (7 years for men) aged 75-84 and 20 years for women (18 years for men) aged 45-54 years, whereas cancer was the major cause of death for women younger than 75 years whatever the time since diagnosis for breast and for all patients younger than 75 years for lung cancer. In contrast, deaths from other causes were more frequent in all the patients older than 75 years. Apart from breast cancer in women younger than 55 years and lung cancer in women older than 55 years and men older than 65 years, the probability of death from cancer among prevalent cases fell below 1%, with varying times since diagnosis. The authors' approach can be used to better describe the burden of cancer by estimating outcomes in prevalent cases.

POSC77 Incorporating Possibility of Cure into Cost Utility Analysis for Nivolumab in Adjuvant Treatment of Resected Stage III/IV Melanoma in France

Long-term plateaus and heterogeneity in survival due to the possibility of cure with immuno-oncologic therapies is often analyzed by mixture cure models (MCMs). This analysis aimed to demonstrate the impact of accounting for cured patients on the cost-effectiveness (CE) profile of nivolumab versus observation in adjuvant treatment of melanoma from a societal perspective in France.

Real-world effectiveness of pembrolizumab in advanced melanoma: analysis of a French national clinicobiological database.

Aim: To describe real-world pembrolizumab administration and outcomes for advanced melanoma in France. Materials & methods: Using the MelBase longitudinal database, this multicenter historical-prospective study examined treatment and outcomes of patients with nonuveal, unresectable stage III/IV melanoma initiating pembrolizumab from April2016 to September2017, with follow-up to September 2019. Kaplan-Meier time-to-event analyses were conducted. Results: Of 223 patients (median age 67; 51% men), 134 (60%), 36 (16%) and 53 (24%) initiated pembrolizumab in first-, second- and third-line, respectively. Median overall survival (months) was 32.6 (95% CI: 20.3-not reached [NR]), 14.4 (8.6-NR)and 9.3 (6.4-NR), respectively. Best real-world tumor response of complete or partial response was recorded for 49, 39 and 26% of patients, respectively. Conclusion: Study results support benefits of pembrolizumab therapy for advanced melanoma.

Cost–Utility Analysis of Nivolumab in Adjuvant Treatment of Melanoma in France

IntroductionThe aim of the current study is to estimate the cost-effectiveness of adjuvant treatment with nivolumab relative to clinically relevant comparators in adult patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection from a French societal perspective.MethodsThe comparators were observation, low-dose interferon and pembrolizumab. A subgroup analysis was carried out in patients with BRAF mutation, adding dabrafenib plus trametinib. A three-state partitioned survival model was developed to project costs and health benefits over a 20-year time horizon. Extrapolation for recurrence-free survival (RFS) and overall survival (OS) was carried out using spline-based models. Because of the immaturity of OS data in pivotal trials for nivolumab and pembrolizumab, a predictive model of OS treatment effect based on RFS effect was developed using a correlation equation. Health state utilities and adverse events disutilities were derived from the CheckMate 238 trial and literature. Costs were estimated in 2019 euros. The model’s primary outcome was efficiency frontier. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of results.ResultsObservation, low-dose interferon and nivolumab were on the efficiency frontier. The incremental cost–utility ratio of nivolumab versus low-dose interferon (closest therapy on the efficiency frontier) was €37,886/quality-adjusted life year (QALY). Probabilistic sensitivity analysis reported an 80% probability of nivolumab being a cost-effective strategy for a willingness-to-pay threshold of €52,000/QALY. In the subgroup with BRAF mutation, the efficiency frontier was not changed by the addition of dabrafenib plus trametinib.ConclusionsNivolumab is a cost-effective strategy as adjuvant treatment in adult patients with surgically resected melanoma in France.Electronic supplementary materialThe online version of this article (10.1007/s13555-020-00446-z) contains supplementary material, which is available to authorized users.

PCN66 A COST-UTILITY ANALYSIS OF NIVOLUMAB IN THE ADJUVANT TREATMENT OF MELANOMA IN FRANCE

The anti-PD1 nivolumab, as monotherapy, is indicated for adjuvant treatment of adults with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection. We conducted a cost-utility analysis with the objective of evaluating nivolumab efficiency in France. A 3-state partitioned survival model, comprising recurrence-free survival (RFS), post-recurrence survival and death simulated a cohort of French patients within the adjuvant indication over 20 years. Standard recommended comparators, matching the population of indication, were observation and low dose interferon (LD-IFN). The model used clinical data from pivotal phase III trial Checkmate 238 comparing nivolumab to ipilimumab. Ipilimumab, not approved for adjuvant treatment of melanoma in Europe, was used as connecting strategy within the network meta-analysis used to estimate relative efficacy of nivolumab versus comparators. RFS and overall survival (OS) were extrapolated with parametric distributions using as reference the placebo arm from study CA184-029. As OS data is not available in CheckMate 238 to date, a predictive model based on RFS-OS correlation equation was used; as scenario, nivolumab OS was conservatively assumed equivalent to ipilimumab OS in CA184-029. Utilities were derived from EQ-5D data collected in Checkmate 238. Costs consisted of acquisition and administration, monitoring, subsequent therapies, palliative care, adverse events and transportation. Costs for active treatments were based on drug public prices. In both base case and conservative scenarios, nivolumab respectively resulted in a discounted total of 9.62 and 8.47 life-years and 7.76 and 6.97 quality-adjusted life years (QALY). The efficiency frontier consisted of observation, LD-IFN and nivolumab. The incremental cost-utility ratio (ICUR) of nivolumab was respectively 34,620 €/QALY and 68,928 €/QALY versus LD-IFN (incremental costs: 44,992 € and 35,667 €, incremental QALY: 1.30 and 0.52). Using two different scenarios, this analysis suggested that nivolumab was a cost-effective strategy as adjuvant treatment of adults with melanoma in France.

104P - First national external quality assessment for the interpretation of somatic variants: Assessment of 25 variants in colorectal, lung, ovarian cancers and melanoma in France

BackgroundThe interpretation of testing results in molecular pathology is an essential phase. It is difficult to assesss this in external quality assessment on real samples. Here we propose a national measure of the concordance in the variant interpretation between laboratories participating in the national French quality control program Gen&tiss. MethodsLaboratories were asked to interpret 5 variants each for melanoma, lung and colorectal cancers and 10 for ovarian cancer. These variants in KRAS, NRAS, BRAF, PIK3CA, PTEN, AKT1, TP53, EGFR, RAC1, KIT, BRCA1 and BRCA2 were not classical hotspots of mutation and 15 of these were annotated in OncoKB. A maximum of 25 variants was assessed per laboratories. Nine possible interpretations were proposed: from neutral to oncogenic and from no therapeutic impact to targeted by a drug. For each variant, a consensus score was determined based on public database as OncoKb and validated by 4 molecular experts with literature review. Three scores were possible: right answer (2 points), acceptable answer without clinical impact (1 point), wrong answer with clinical impact (0 points). Results60 laboratories participated to the program for variant interpretation. The average scores on 10 were 5.9 for colorectal (N=52), 7.0 for lung (N=49), 6.0 for melanoma (N=49) and 7.0 for ovarian cancer (N=25). For BRCA genes in ovarian cancer, there was a pilot project in 2017, in which 5 identical variants were proposed to interpretation. 18 laboratories participated both in 2017 and 2018: 50% performed better, 28% performed worse, 17% had similar results. ConclusionsAs test results have will have a direct impact on patient management, ensuring a correct interpretation becomes more and more important. This EQA could help to validate the interpretation process used in the laboratories (SOP and databases) and could be extend to the individual expertise.The average score is acceptable, yet improvable and it really depends on the variants proposed. International consensus guidelines equivalent to the ACMG classification of constitutional variants would be helpful to improve reproducibility and inter-laboratory homogeneity. Legal entity responsible for the studyGen&tiss - GFCO and AFAQAP. FundingAstraZeneca. DisclosureAll authors have declared no conflicts of interest.

Cutaneous melanoma in France in 2015 attributable to solar ultraviolet radiation and the use of sunbeds.

Exposure to solar ultraviolet radiation (UVR) and the use of UV-emitting tanning devices are associated with cutaneous malignant melanoma occurrence. The aim of this study was to quantify the proportion and number of melanoma cases attributable to solar UVR exposure and sunbed use in France in 2015. Population attributable fractions (PAFs) and numbers of melanoma cases attributable to solar UVR exposure were estimated by age and sex using the incidence rates of a 1903 birth cohort as the primary reference. Further analyses were performed using the following: (i) contemporary melanoma incidence rates in low-incidence regions within France and (ii) national melanoma incidence rates for the year 1980, as additional references. Assuming a 15-year lag period, PAF and melanoma cases attributable to sunbed use were calculated using prevalence estimates from a cross-sectional population survey and published relative risk estimates. In 2015, an estimated 10 340 melanoma cases diagnosed in French adults were attributable to solar UVR exposure, corresponding to 83% of all melanomas and 3% of all cancer cases in that year. PAFs for melanoma were highest in the youngest age group (30-49 years) and higher in men than in women (89% vs. 79%). A total of 382 melanoma cases occurring in French adults in 2015 were attributed to the use of sunbeds, equivalent to 1.5% and 4.6% of all melanoma cases in men and women, respectively. A considerable proportion of melanoma cases in France in 2015 were attributable to solar UVR exposure, suggesting that targeted prevention strategies need to be implemented.

Economic burden of advanced melanoma in France, Germany and the UK: a retrospective observational study (Melanoma Burden-of-Illness Study).

The aim of this study was to estimate the cost-of-illness associated with completely resected stage IIIB/IIIC melanoma with macroscopic lymph node involvement, overall and by disease phase, in France, Germany and the UK. This retrospective observational study included patients aged older than or equal to 18 years first diagnosed with stage IIIB/IIIC cutaneous melanoma between 1 January 2009 and 31 December 2011. Data were obtained from medical records and a patient survey. Direct costs, indirect costs and patient out-of-pocket expenses were estimated in euros (€) (and British pounds, £) by collecting resource use and multiplying by country-specific unit costs. National annual costs were estimated using national disease prevalence from the European cancer registry and other published data. Forty-nine centres provided data on 558 patients (58.2% aged <65 years, 53.6% stage IIIB disease at diagnosis). The mean follow-up duration was 27 months (France), 26 months (Germany) and 22 months (UK). The mean total direct cost per patient during follow-up was €23 582 in France, €32 058 in Germany and €37 970 (£31 123) in the UK. The largest cost drivers were melanoma drugs [mean €14 004, €21 269, €29 750 (£24 385), respectively] and hospitalization/emergency treatment [mean: €6634, €6950, €3449 (£2827), respectively]. The total mean indirect costs per patient were €129 (France), €4,441 (Germany) and €1712 (£1427) (UK). Estimates for annual national direct cost were €13.1 million (France), €30.2 million (Germany) and €27.8 (£22.8) million (UK). The economic burden of stage IIIB/IIIC melanoma with macroscopic lymph node involvement was substantial in all three countries. Total direct costs were the highest during the period with distant metastasis/terminal illness.

Estimation of The Cost of Metastatic Melanoma in France Using Melbase Data

Estimation of The Cost of Metastatic Melanoma in France Using Melbase Data

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

BackgroundManagement 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.MethodsThe 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).ResultsSeventy-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.ConclusionsHospitalisation 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.

Treatment patterns and outcomes of Stage IIIB/IIIC melanoma in France, Germany and the UK: A retrospective and prospective observational study (MELABIS).

SummaryAimReal‐world data on treatment patterns/outcomes in patients with advanced melanoma, while scarce, are useful for health technology assessments that govern patient access in many countries. We collected retrospective data on treatment patterns among patients in France, Germany and the UK with Stage IIIB/IIIC melanoma with macroscopic lymph node involvement, whose primary melanoma and regional lymph node metastases had been completely resected.MethodsPatients ≥18 years were diagnosed between 1 January 2009 and 31 December 2011. Data were obtained from patients’ medical records and a patient survey.ResultsForty‐nine centres provided data on 558 patients: 53.6% had Stage IIIB disease; 58.2% were of working age (<65 years), 22.5% reported a change in employment status due to melanoma, 8% were on long‐term sick leave; and 35.1% were deceased over the study period. Overall median distant metastases‐free survival was 23.4 months and median disease‐free survival was 13.3 months. Hospitalisation frequency increased during distant metastatic/terminal disease phases. Adjuvant therapy was received by 7.0% (14/199) of patients in France, 2.6% (5/195) in the UK, and 33.5% (55/164) in Germany. Low‐dose interferon was used more frequently than other regimens. High‐dose interferon was associated with discontinuation in 28.6% and dose delay/reduction in 33.3% of patients.ConclusionsRapid disease progression combined with increased use of healthcare resources in later phases of disease result in a high burden‐of‐illness for patients and healthcare providers. The use of adjuvant interferon therapy varies considerably in this population in the countries studied, highlighting the need for improved treatments for melanoma.

PCN70 - Cost of 1st Line Treatment Failure in Braf V600 Mutated Metastatic Melanoma in France

PCN70 - Cost of 1st Line Treatment Failure in Braf V600 Mutated Metastatic Melanoma in France

End-of-life care for hospitalized patients with metastatic melanoma in France: a nationwide, register-based study.

Although the aggressiveness of end-of-life cancer care has come under great scrutiny over the past two decades, little is known about the intensity of care and treatments in the last months of life of patients with metastatic melanoma. To measure the prevalence of aggressive cancer care use, and to assess the frequency of palliative care referral over the course of the last 3 months of life of hospitalized patients who died from metastatic melanoma. A nationwide register-based study in France was carried out, including all hospitalized adults aged ≥ 20 years who died from metastatic melanoma in metropolitan France between 2010 and 2013. Of 3889 patients who died from metastatic melanoma, 51·9% received chemotherapy in the last 3 months before death, 25·9% in the last month, 12·9% in the last 2 weeks and 7·6% in the last week. On average, patients were hospitalized for 31·7 days over the course of their last 3 months of life. During the final month before death, 12·0% of patients received radiation therapy, 14·0% received blood transfusion, 12·1% were transferred into an intensive care unit and 19·7% remained hospitalized continuously. Palliative care needs were identified in 78·4% of patients, with variations according to the type of facility. In total 17% of all patients died in palliative care inpatient units. Treatment intensity near the end of life of patients with metastatic melanoma raises concerns for the quality of care. There is a need for clinical guidelines and adequate support to facilitate patient-physician communication and to improve access to palliative care services.

PCN99 - An Assessment of The Hospitalization Costs of Melanoma in France in the Advanced/Metastatic Setting: the Melissa Study (Melanoma in Hospital Costs Assessment)

PCN99 - An Assessment of The Hospitalization Costs of Melanoma in France in the Advanced/Metastatic Setting: the Melissa Study (Melanoma in Hospital Costs Assessment)

1216 An assessment of the hospitalization costs of melanoma in France in the advanced/metastatic setting: The MELISSA study (MELanoma In hoSpital coSts Assessment)

1216 An assessment of the hospitalization costs of melanoma in France in the advanced/metastatic setting: The MELISSA study (MELanoma In hoSpital coSts Assessment)

EDIFICE Melanoma survey: knowledge and attitudes on melanoma prevention and diagnosis

Melanoma incidence is increasing worldwide thus justifying information campaigns aimed at reducing ultraviolet exposure levels and promoting early diagnosis. We set out to assess awareness, knowledge and attitudes of the French population with regard to melanoma prevention and early diagnosis, following more than 15 years of nationwide information campaigns. The French nationwide observational survey, EDIFICE Melanoma, was conducted after the summer (September to October 2011) through structured telephone interviews of a representative sample of 1502 individuals aged ≥18 years, using the quota method. All French regions were represented. Respondents had heard of sun-induced skin damage: 92% knew that sun increases melanoma risk. Knowledge of sun-protection measures was also good: 97% correctly cited at least one method of photoprotection (clothing 80%, sunscreens 69%) and 97% declared that sun exposure should be reduced between 12 pm and 4 pm in France. Knowledge of melanoma was encouraging: 70% of respondents could define the disease accurately and 60% knew the ABCDE rule for early diagnosis. However, self-tanning and sunbed use were considered by 25% and 13% of respondents, respectively, to provide protection from skin cancer. Although 43% of respondents (58% of high-risk respondents) declared they had consulted a doctor at least once for a suspect skin lesion, their actual behaviour was less encouraging: 30% declared never or almost never protecting their skin; 25% declared regularly checking their skin for atypical nevi; 12% declared checking the entire skin surface. Declared behaviour was better in fair-skin responders and those with a history of sunburn or skin cancer. Awareness of melanoma, early-diagnosis procedures and preventive behaviour has improved in the general French population since 1990. However, despite the good level of information, numerous misconceptions persist. Improved information campaigns in the future may help reduce the ever-increasing incidence of melanoma in France.

Skin cancer in the UK and the role of early detection

British Journal of Healthcare ManagementVol. 20, No. 10 CommentSkin cancer in the UK and the role of early detectionNina Goad, Matthew GassNina GoadSearch for more papers by this author, Matthew GassSearch for more papers by this authorNina Goad; Matthew GassPublished Online:6 Nov 2014https://doi.org/10.12968/bjhc.2014.20.10.458AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References British Association of Dermatologists (2014) ABCD-Easy guide to checking your moles. Available at: www.bad.org.uk/for-the-public/skin-cancer/melanoma-leaflets/abcd-easy-guide-to-checking-your-moles (accessed 30 September 2014) Google ScholarGrange F, Woronoff AS, Bera R (2014) Efficacy of a general practitioner training campaign for early detection of melanoma in France. Br J Dermatol 170(1): 123–9 Crossref, Google ScholarNational Institute for Health and Care Excellence (2010) Improving Outcomes for People with Skin Tumours including Melanoma. CSGSTIM. NICE, London Google ScholarPoirier V, Jones T, Ives A, Newton-Bishop J, Verne J (2014) (Poster 145) Skin Cancer Care in England. XV World Congress on Cancers of the Skin. 3–6 October, Edinburgh Google Scholar FiguresReferencesRelatedDetails 2 October 2014Volume 20Issue 10ISSN (print): 1358-0574ISSN (online): 1759-7382 Metrics History Published online 6 November 2014 Published in print 2 October 2014 Information© MA Healthcare LimitedPDF download

Treatment Patterns and Disease Burden of Stage Iiib/Iiic Melanoma in France, Germany and the Uk

ABSTRACT Aim: Real-world data on treatment patterns and costs are often scarce, although much needed for health technology assessments governing patient access in many countries. This study aimed to collect these data in France, Germany and the UK for patients with stage IIIB/IIIC melanoma with macroscopic lymph node involvement, whose primary melanoma and regional lymph node metastases had been completely resected. Methods: This retrospective observational study enrolled patients aged ≥18 years first diagnosed between 1 January 2009 and 31 December 2011. Data were extracted from patients' medical records until death or study end date, and via a patient survey. Costs were calculated by collecting resource use and multiplying by unit costs. Results: 49 centres provided data on 558 patients. Overall, 56% of patients were male and 58% were aged Adjuvant systemic therapy received, n (%) France Germany UK None 185 (93.0) 109 (66.5) 190 (97.4) Interferon High dose 3 (1.5) 18 (11.0) 0 intermediate dose 1 (0.5) 8 (4.9) 0 low dose 0 25 (15.2) 0 pegylated 0 3 (1.8) 0 Other 10 (5.0) 1 (0.6) 5 (2.6) Total 199 164 195 Conclusions: Although the great majority of patients received no adjuvant treatment in France (93%) and the UK (97.4%), there was some use of interferon in Germany (high dose 11%; intermediate dose 5%; low dose 15%; pegylated 2%). Relatively high direct costs were observed in all three countries. Disclosure: P. Mohr: PM received consulting fees and honoraria fees from GlaxoSmithKline group of companies, Roche, Merck, SciBase, Bristol-Myers Squibb, Novartis and Leo. He also received research funding from Merck; M. Harries: MH has received honoraria from GlaxoSmithKline group of companies for advisory boards; F. Grange: FG acted as an investigator in GlaxoSmithKline group of companies' studies and as a scientific advisor for GlaxoSmithKline group of companies; R. Ehness: RE is an employee of the GlaxoSmithKline group of companies and holds stock or stock options or restricted shares in GlaxoSmithKline group of companies; L. Benjamin: LB is an employee of the GlaxoSmithKline group of companies and holds stock or stock options or restricted shares in GlaxoSmithKline group of companies; O. Siakpere: OS is an employee of the GlaxoSmithKline group of companies and holds stock or stock options or restricted shares in GlaxoSmithKline group of companies; L. McLeod: LM is full-time employees of RTI Health Solutions, which received funding from GlaxoSmithKline group of companies to conduct this study; S. Wolowacz: SW is full-time employees of RTI Health Solutions, which received funding from GlaxoSmithKline group of companies to conduct this study; J.A. Kaye: JAK is full-time employees of RTI Health Solutions, which received funding from GlaxoSmithKline group of companies to conduct this study. I. Kontoudis: IK is an employee of the GlaxoSmithKline group of companies.