Cost Effectiveness of Intra-Articular Hyaluronic Acid and Disease-Modifying Drugs in Knee Osteoarthritis

Abstract

Background

The place of disease-modifying osteoarthritis drugs (DMOADs) and intra-articular hyaluronic acid (IAHA) in the therapeutic arsenal for knee osteoarthritis (OA) remains uncertain. Indeed, these treatments have demonstrated symptomatic efficacy but no efficacy for disease modification.

Objective

This report reviews the cost effectiveness of IAHA and DMOADs used in the treatment of knee OA.

Methods

A systematic literature search of the MEDLINE, Scopus, EMBASE and Cochrane databases was performed independently by two rheumatologists who used the same predefined eligibility criteria to identify relevant articles. Papers without abstracts and in languages other than English or French were excluded. Extracted costs were annualised and converted to 2015 euros (€) using the Consumer Price Index of the relevant countries and the 2013 Purchasing Power Parities between these countries and the European Union average.

Results

A total of 95 abstracts were selected, and 13 articles were considered for the review: nine articles on IAHA and four on DMOADs. Only one article directly compared different IAHA compounds. Articles showed substantial heterogeneity in methodological approaches. The incremental cost-effectiveness ratios (ICERs) ranged from €4000 to €57,550 and from €240 to €53,225 per quality-adjusted life-year (QALY) gained for DMOADs and IAHA, respectively.

Conclusions

This review highlights substantial heterogeneity between studies, ranging from a cost saving (or dominating) position to very high ICERs, far above the acceptability threshold of €50,000/QALY. Additional research is needed to determine reliable and robust ICER estimates for knee OA therapies.

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Utility Values for Health States in Ireland: A Value Set for the EQ-5D-5L

Abstract

Objective

Our objective was to develop a value set based on Irish utility values for the EuroQol 5-Dimension, 5-Level instrument (EQ-5D-5L).

Methods

The research design and data collection followed a protocol developed by the EuroQol Group. The EuroQol Valuation Technology (EQ-VT) software was administered using computer-assisted personal interviews to a representative sample of adults resident in Ireland between 2015 and 2016. Utility values were elicited using two stated-preference techniques: time trade-off (TTO) and discrete-choice experiment (DCE). Each respondent completed a valuation exercise in which the EQ-VT system randomly selected one block of ten TTO questions from ten blocks relating to a possible 86 health states. One block of seven DCE pairs from 28 blocks of a possible 196 pairs of health states were randomly selected to accompany this. The relationship between utility values and health states was analysed using a hybrid regression model that combined data from the TTO and DCE techniques and expressed these as a function of the health state presented to the individual. This model estimated coefficients for 20 dummy variables that characterised each health state in the EQ-5D-5L framework, with the lowest level of severity providing the reference category in each domain. The relationship between weighted and unweighted TTO and DCE analyses of main effects was analysed separately.

Results

Comparison of weighted and unweighted models revealed no substantive differences in results with respect to either DCE or TTO models. The unweighted hybrid model produced estimated effects, the ordering of which was intuitively consistent within each domain: lower levels of health were associated with lower utility values. Differences were evident between domains with respect to valuations; the disutility associated with conditions related to anxiety/depression and pain/discomfort was higher than for other domains. The decrement in utility associated with movement from the highest to the lowest level of health was 0.344 for mobility, 0.287 for self-care, 0.187 for usual activities, 0.510 for pain/discomfort and 0.646 for anxiety/depression.

Discussion

The results present the first value set based on the EQ-5D-5L framework for a representative sample of residents in Ireland. The set reveals a higher decrement in utility associated with anxiety/depression than with other domains of health. Caution is warranted in comparisons with other value sets. That said, those in England, the Netherlands, Uruguay and China reveal that, whereas Irish values are broadly consistent with respect to mobility, self-care and usual activities, residents of Ireland attach a higher decrement to pain/discomfort and anxiety/depression than do other populations.

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Nivolumab for Treating Metastatic or Unresectable Urothelial Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Abstract

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Bristol-Myers Squibb) of nivolumab (Opdivo^®) to submit evidence of its clinical and cost effectiveness for metastatic or unresectable urothelial cancer. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG), which produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company's submission to NICE. Nivolumab was compared with docetaxel, paclitaxel, best supportive care and retreatment with platinum-based chemotherapy (cisplatin plus gemcitabine, but only for patients whose disease has had an adequate response in first-line treatment). Two ongoing, phase I/II, single-arm studies for nivolumab were identified, but no studies directly compared nivolumab with any specified comparator. Evidence from directly examining the single arms of the trial data indicated little difference between the outcomes measured from the nivolumab and comparator studies. A simulated treatment comparison (STC) analysis was used in an attempt to reduce the bias induced by naïve comparison, but there was no clear evidence that risk of bias was reduced. Multiple limitations in the STC were identified and remained. The effect of an analysis based on different combinations of covariates in the prediction model remains unknown. The ERG's concerns regarding the economic analysis included the use of a non-established response-based survival analysis method, which introduced additional uncertainty. The use of time-dependent hazard ratios produced overfitting and was not represented in the probabilistic sensitivity analysis. The use of a treatment stopping rule to cap treatment cost left treatment effectiveness unaltered. A relevant comparator was excluded from the base-case analysis. The revised ERG deterministic base-case incremental cost-effectiveness ratios based on the company's Appraisal Consultation Document response were £58,791, £78,869 and £62,352 per quality-adjusted life-year gained versus paclitaxel, docetaxel and best supportive care, respectively. Nivolumab was dominated by cisplatin plus gemcitabine in the ERG base case. Substantial uncertainties about the relative treatment effectiveness comparing nivolumab against all comparators remained. NICE did not recommend nivolumab, within its marketing authorisation, as an option for treating locally advanced, unresectable or metastatic urothelial carcinoma in adults who have had platinum-containing therapy, and considered that nivolumab was not suitable for use within the Cancer Drugs Fund.

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Comparative cardio and developmental toxicity induced by the popular medicinal extract of Sutherlandia frutescens (L.) R.Br. detected using a zebrafish Tuebingen embryo model

Sutherlandia frutescens is one of the most promising commercialized, indigenous and medicinal plants of South Africa that is used as an immune-booster, and a traditional treatment for cancer. However, few studies...

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In order to ensure that evidence is unbiased it is sometimes necessary to retreat to the scientific ivory tower

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Sequential MRI in pontine and extrapontine myelinolysis following rapid correction of hyponatremia

This study describes the MRI changes associated with pontine and extrapontine myelinolysis secondary to rapid correction of hyponatremia in dogs. The authors discuss the relevance of the results for theories o...

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A conditional Pax6 depletion study with no morphological effect on the adult mouse corneal epithelium

The corneas of heterozygous Pax6+/− mice develop abnormally and deteriorate further after birth but it is not known whether the postnatal deterioration is predetermined by abnormal development. Our objective was ...

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