Systematic Literature Review to Assess Economic Evaluations in Spinal Muscular Atrophy (SMA)

Abstract

Background Spinal muscular atrophy (SMA) is a rare, progressive neuromuscular disease that affects individuals with a broad age range. SMA is typically characterised by symmetrical muscle weakness but is also associated with cardiac defects, life-limiting impairments in respiratory function and bulbar function defects that affect swallowing and speech. Despite the advent of three innovative disease-modifying therapies (DMTs) for SMA, the cost of DMTs in addition to the costs of standard of care can be a barrier to treatment access for patients. Health Technology Assessment (HTA) decision makers evaluate the cost effectiveness of a new treatment before making a reimbursement decision. Objective The primary objective was to conduct a systematic literature review (SLR) to identify the modelling approaches used in economic evaluations that assess current approved treatments in SMA, with a secondary objective to widen the scope and identify economic evaluations assessing other (non-SMA) neuromuscular disorders. Methods An SLR was performed to identify available economic evaluations associated with any type of SMA (Type 1, 2, 3 and/or 4). Economic evaluations associated with other (non-SMA) neuromuscular disorders were identified but not further analysed. Electronic searches were conducted in Embase, MEDLINE, Evidence-Based Medicine Reviews and EconLit via the Ovid platform in August 2019, and were supplemented by searches of the grey literature (reference lists, conference proceedings, global HTA body websites and other relevant sources). Eligibility criteria were based on the population, interventions, comparators and outcomes (PICO) framework. Quality assessment of full publications was conducted with reference to a published checklist. Results Nine publications covering eight unique studies met all eligibility criteria for inclusion in the SLR, including four conference abstracts, two peer-reviewed original research articles and three HTA submissions (conducted in Canada, the US and the UK). Evaluations considered patients with early infantile-onset (most likely to develop Type 1 or Type 2 SMA), lateronset SMA and both infantile-and later-onset SMA. Data for the identified economic models were collected from literature reviews and relatively short-term clinical trials. Several intent-to-treat clinical trial populations were used in the studies, which resulted in variation in cycle length and different outcome measures to determine clinical efficacy. The results of the quality assessment on the five full-text, peer-reviewed publications found that they generally provided clear descriptions of objectives, modelling methods and results. However, key decisions, such as choice of economic evaluation, model type and choice of variables for sensitivity analysis, were often not adequately justified. Conclusions This SLR highlights the need for economic evaluations in SMA to better align in modelling approaches with respect to (i) consistency in model structure and use of motor function milestones as health states; (ii) con...

Dramatic Innovations in the Treatment of Spinal Muscular Atrophy, But Many Unknowns Remain

“…A review of economic evaluations of SMA DMTs by Paracha et al [12] notes how these limitations in estimates of both cost and utilities have led to inconsistencies between different economic models used in HTAs. They identify differences in model structure and functional endpoints; methods for indirectly mapping patient-reported outcomes to preference measures; and the inclusion of carer utilities.…”

Systematic Literature Review to Identify Utility Values in Patients with Spinal Muscular Atrophy (SMA) and Their Caregivers

“…patient age for SMA), (3) standardisation of utility data collection across clinical trials of an intervention, and (4) considerations of how trial sample size will affect uncertainty of utility estimates [28]. Recommendations for study design and methodological approaches for economic evaluations in SMA have been recently published in an SLR [89].…”

Importance of Patient Involvement in the Value Assessment Process: On the Way Towards Personalised Treatments

“…Decisions taken in the design of clinical trials regarding the assessed endpoints and eligibility criteria will directly impact the understanding of the value of a product later; especially because value assessments tend to focus on selected subsets of clinical outcomes because these were the endpoints studied in trials [8][9][10]. Today, patient-reported outcomes are often generic and miss-ing patient relevance for a specific disease environment.…”

“…In spinal muscular atrophy (SMA), endpoints are predominantly clinical outcomes and not necessarily patient-relevant. Outcomes focus heavily on motor function as health states [9,12] and tend to neglect other aspects, such as performing daily activities, fatiguability, fatigue, pain, psychological issues, or swallowing, which seem to be impacting wellbeing in patients [13,14]. Similarly, other meaningful motor-functional changes, such as fine finger movements that allow better communication via electronic devices, are not captured by current scales [15].…”

“…In SMA, the challenges we face in value assessments are typical for the field of rare diseases; specific instruments are not available and tailored methods are missing [9,17,18]. Particularly challenging are heterogenous and often non-transparent processes with lack of patient expert involvement, the lack of data about what attributes matter most to patients, and as a result the missing knowledge of the involved actors in this regard, limited life history data, lack of validated and disease-specific methods to assess quality of life, especially in the paediatric population, small study sample sizes and lack of long-term clinical data across different subpopulations (see also [9]).…”