Patterns of Tumor Necrosis Factor Inhibitor (TNFi) Biosimilar Use Across United States Rheumatology Practices.

ObjectiveIt is unclear if biosimilars of biologics for inflammatory arthritis are realizing their promise to increase competition and improve accessibility. This study evaluates biosimilar tumor necrosis factor inhibitor (TNFi) utilization across rheumatology practices in the United States and compares whether patients initiating biosimilars remain on these treatments at least as long as new initiators of bio-originators.MethodsWe identified a cohort of patients initiating a TNFi biosimilar between January 2017 and September 2018 from an electronic health record registry containing data from 218 rheumatology practices and over 1 million rheumatology patients in the United States. We also identified a cohort of patients who initiated the bio-originator TNFi during the same period. We calculated the proportion of biosimilar prescriptions compared with other TNFi's and compared persistence on these therapies, adjusting for age, sex, diagnoses codes, and insurance type.ResultsWe identified 909 patients prescribed the biosimilar infliximab-dyyb, the only biosimilar prescribed, and 4413 patients with a new prescription for the bio-originator infliximab. Biosimilar patients tended to be older, have a diagnosis code for rheumatoid arthritis, and covered by Medicare insurance. Over the study period, biosimilar prescriptions reached a maximum of 3.5% of all TNFi prescriptions. Patients persisted on the biosimilar at least as long as the bio-originator infliximab (hazard ratio [HR] 0.83, P = 0.07).ConclusionThe uptake of biosimilars in the United States remains low despite persistence on infliximab-dyyb being similar to the infliximab bio-originator. These results add to clinical studies that should provide greater confidence to patients and physicians regarding biosimilar use

Implausible states: prevalence of EQ-5D-5L states in the general population and its effect on health state valuation

The EQ-5D is made up of health state dimensions and levels, in which some combinations seem less “plausible” than others. If “implausible” states are used in health state valuation exercises, then respondents may have difficulty imagining them, causing measurement error. There is currently no standard solution: some valuation studies exclude such states, whereas others leave them in. This study aims to address 2 gaps in the literature: 1) to propose an evidence-based set of the least prevalent two-way combinations of EQ-5D-5L dimension levels and 2) to quantify the impact of removing perceived implausible states from valuation designs. For the first aim, we use data from 2 waves of the English General Practitioner Patient Survey (n = 1,639,453). For the second aim, we remodel a secondary data set of a Discrete Choice Experiment (DCE) with duration that valued EQ-5D-5L and compare across models that drop observations involving different health states: 1) implausible states as defined in the literature, 2) the least prevalent states identified in stage 1, and 3) randomly select states, alongside 4) a model that does not drop any observations. The results indicate that two-way combinations previously thought to be implausible actually exist among the general population; there are other combinations that are rarer, and removing implausible states from an experimental design of a DCE with duration leads to value sets with potentially different characteristics depending on the criterion of implausible states. We advise against the routine removal of implausible states from health state valuation studies

Using a discrete choice experiment to estimate societal health state utility values

In this study we explore a novel application of the Discrete Choice Experiment (DCE) that resembles the Time Trade Off (TTO) task to estimate values on the health utility scale for the EQ-5D. The DCE is tested in a survey alongside the TTO in respondents largely representative of the Canadian general population. The study finds that the DCE is able to derive logical and consistent values for health states valued on the full health – dead scale. The DCE overcame some issues identified in the version of TTO currently used to value EQ-5D, notably whether to exclude respondents who fail to understand the task and incorporating values considered worse than dead without transformation. This has important implications for providing values that represent the preferences of all respondents

Preparatory study for the revaluation of the EQ-5D tariff: methodology report.

BACKGROUND: EQ-5D is a widely used generic measure of health with a 'tariff', or preference weights, obtained from the general population, using time trade-off (TTO). PRET (Preparatory study for the Re-valuation of the EQ-5D Tariff project) contributes towards the methodology for its revaluation. METHODS: Stage 1 examined key assumptions typically involved in health-state valuations through a series of binary choice exercises, namely that health-state preferences are independent of (1) duration of the state; (2) whose health it is (i.e. perspective); (3) length of 'lead time' (a mechanism to value all states on the same scale, including those who are worse than being dead); (4) when health events take place (time preference); and (5) satisfaction associated with the state. Further topics addressed were (6) exhaustion of lead time in the worst state; (7) health-state valuation using discrete choice experiments (DCEs) with a duration attribute; and (8) binary choice administration of lead time - time trade-off (LT-TTO). Stage 1 consisted of an online survey with 6000 respondents. Stage 2 compared the results above to those of an identical survey conducted in 200 face-to-face computer-assisted personal interviews (CAPIs), covering topics (1) to (7). Stages 3 and 4 examined - in more detail and depth - issues taken from stage 1. Stage 3 consisted of CAPI surveys of a representative UK sample of 300, using examples of TTO, LT-TTO, and DCE with duration, each followed by extensive feedback questions. Stage 4 was a more intensive exercise involving a qualitative analysis of people's thought processes during both binary choice and iterative health-state valuation exercises. Data were collected through 'think-aloud' methods in 30 interviews of a convenience sample. RESULTS: Stage 1 found that health-state values are not independent of (1) duration of the state but there is no clear pattern; (2) whose health it is; (3) the duration of 'lead time' but there was no clear pattern; (4) when health events take place; or (5) satisfaction associated with the state. Furthermore, (6) exhaustion of lead time in the worst state was subject to substantial framing effects; (7) the five-level version of the EQ-5D (EQ-5D-5L) can be valued using DCE with duration as an attribute; and (8) binary choice LT-TTO can be administered in an online environment. Stage 2 found that although online surveys and CAPI surveys resulted in different compositions of respondents, at the aggregate, their responses to the experimental questions covering (1) to (7) above were not statistically significantly different from each other. Stages 3 and 4 found that TTO and LT-TTO were easier than DCE with duration; respondents did not necessarily trade across all attributes of EQ-5D; some respondents found it difficult to distinguish between the two worst levels of EQ-5D-5L, and some respondents may be thinking about the impact of their ill health on their family. CONCLUSIONS: In order for the National Institute for Health and Care Excellence to make the most appropriate decisions, the EQ-5D tariff needs to incorporate the latest understanding of health-state preferences. PRET contributed to the knowledge base on the conduct of health-state valuation studies. FUNDING: The Medical Research Council (MRC)-National Institute for Health Research (NIHR) Methodology Research Programme funded the PRET project (MRC ref. G0901500), and the EuroQol Group funded the PRET-AS project (Preparatory study for the Re-valuation of the EQ-5D Tariff project - Additional Sample) as an extension to the PRET project with formal agreement from the MRC

Respondent Understanding in Discrete Choice Experiments : A Scoping Review

Acknowledgements The authors would like to acknowledge the contributions of Brendan Mulhern, who gave feedback on the initial project proposal and helped with the full-text reviews, and Bernadette Carr, the librarian who gave assistance developing and implementing the search strategy. Funding During part of this project, Alison Pearce was supported by a University of Technology Sydney Chancellor’s Postdoctoral Research Fellowship and the University of Technology Sydney International Researcher Development Scheme. Mark Harrison is supported by a Michael Smith Foundation for Health Research Scholar Award 2017 (#16813), and holds the UBC Professorship in Sustainable Health Care, which, between 2014 and 2017, was funded by Amgen Canada, AstraZeneca Canada, Eli Lilly Canada, GlaxoSmithKline, Merck Canada, Novartis Pharmaceuticals Canada, Pfizer Canada, Boehringer Ingelheim (Canada), Hoffman-La Roche, LifeScan Canada, and Lundbeck Canada. The Health Economics Research Unit (HERU) receives funding from the Chief Scientist Office (CSO) of the Scottish Government Health and Social Care Directorates.Peer reviewedPublisher PD

Using Discrete Choice Experiment with duration to model EQ-5D-5L health state preferences: Testing experimental design strategies

Background: Discrete choice experiments incorporating duration can be used to derive health state values for EQ-5D-5L. Yet, methodological issues relating to the duration attribute and the optimal way to select health states remain. The aims of this study were to: test increasing the number of duration levels and choice sets where duration varies (aim 1); compare designs with zero and non-zero prior values (aim 2); and investigate a novel, two-stage design to incorporate prior values (aim 3). Methods: Informed by zero and non-zero prior values, two efficient designs were developed, each consisting of 120 EQ-5D-5L health profile pairs with one of six duration levels (aims 1 and 2). Another 120 health state pairs were selected, with one of six duration levels allocated in a second stage based on existing estimated utility of the states (aim 3). An online sample of 2,002 members of the UK general population completed 10 choice sets each. Differences across the regression coefficients from the three designs were assessed. Results: The zero prior value design produced a model with coefficients that were generally logically ordered, but the non-zero prior value design resulted in a set of less ordered coefficients where some differed significantly. The two-stage design resulted in ordered and significant coefficients. The non-zero prior value design may include more “difficult” choice sets, based on the proportions choosing each profile. Conclusions: There is some indication of compromised “respondent efficiency”, suggesting that the use of non-zero prior values will not necessarily result in better overall precision. It is feasible to design discrete choice experiments in two stages by allocating duration values to EQ-5D-5L health state pairs based on estimates from prior studies

Exploring the validity of estimating EQ-5D and SF-6D utility values from the health assessment questionnaire in patients with inflammatory arthritis

<p>Abstract</p> <p>Background</p> <p>Utility scores are used to estimate Quality Adjusted Life Years (QALYs), applied in determining the cost-effectiveness of health care interventions. In studies where no preference based measures are collected, indirect methods have been developed to estimate utilities from clinical instruments. The aim of this study was to evaluate a published method of estimating the EuroQol-5D (EQ-5D) and Short Form-6D (SF-6D) (preference based) utility scores from the Health Assessment Questionnaire (HAQ) in patients with inflammatory arthritis.</p> <p>Methods</p> <p>Data were used from 3 cohorts of patients with: early inflammatory arthritis (<10 weeks duration); established (>5 years duration) stable rheumatoid arthritis (RA); and RA being treated with anti-TNF therapy. Patients completed the EQ-5D, SF-6D and HAQ at baseline and a follow-up assessment. EQ-5D and SF-6D scores were predicted from the HAQ using a published method. Differences between predicted and observed EQ-5D and SF-6D scores were assessed using the paired t-test and linear regression.</p> <p>Results</p> <p>Predicted utility scores were generally higher than observed scores (range of differences: EQ-5D 0.01 - 0.06; SF-6D 0.05 - 0.10). Change between predicted values of the EQ-5D and SF-6D corresponded well with observed change in patients with established RA. Change in predicted SF-6D scores was, however, less than half of that in observed values (p < 0.001) in patients with more active disease. Predicted EQ-5D scores underestimated change in cohorts of patients with more active disease.</p> <p>Conclusion</p> <p>Predicted utility scores overestimated baseline values but underestimated change. Predicting utility values from the HAQ will therefore likely underestimate the QALYs of interventions, particularly for patients with active disease. We recommend the inclusion of at least one preference based measure in future clinical studies.</p

Manipulating the 5 dimensions of the EuroQol instrument: the effects on self-reporting actual health and valuing hypothetical health states

Background. The EQ-5D instrument has 5 dimensions. This article reports on the effects of manipulating a) the order in which the 5 dimensions are presented (appearing first v. last), b) splitting of the composite dimensions (“pain or discomfort” and “anxiety or depression”), and c) removing or “bolting off” 1 of the 5 EQ-5D dimensions at a time. The effects were examined in 2 contexts: 1) self-reporting health and 2) health state valuations. Methods. Three different types of discrete choice experiments (DCE) including a duration attribute were designed. An online survey with 12 subtypes, each with 10 DCE tasks, was designed and completed by 2494 members of the UK general public. Results. Of the 3 manipulations in the self-reporting context, only b) splitting anxiety or depression had a significant effect. In the health state valuation context, b) splitting level 5 pain or discomfort (relative to pain) and splitting level 5 anxiety or depression (relative to anxiety) had significant effects as did c) bolting off dimensions. Conclusions. We find that the values given to certain health dimensions are sensitive to the way in which it is described and the other health dimensions presented. Of particular interest is the effect of splitting composite dimensions: a given EQ-5D(-5L) profile may mean different things depending on whether the profile is used to self-report one’s health or to value hypothetical states, so that the health state values of EQ-5D(-5L) in population tariffs may not correspond to the states that patients self-report themselves in

Proceedings of the 2019 Canadian Inflammatory Myopathy Study Symposium: Clinical Trial Readiness in Myositis.

The Canadian Inflammatory Myopathy Study (CIMS) is a multicenter prospective cohort recruiting in 8 centers across Canada. One of the aims of CIMS is to conduct and participate in clinical trials in autoimmune inflammatory myopathies (AIM). Conducting clinical trials in rare diseases such as AIM presents challenges. During this symposium, experts in the field presented different solutions to successfully conduct clinical trials in AIM, including the importance of collaboration and careful trial design, as well as training and mentoring of young investigators