Cardiometabolic health: evaluating the cost-effectiveness of a diagnostic device
A client wanted us to analyse the cost-effectiveness of a diagnostic device for stroke patients compared to standard treatment. Modelling the cost-effectiveness of any diagnostic device is complex because the value of the diagnostic device is dependent on the value of the treatments available for this condition. This model was particularly challenging because stroke patients can experience a diverse range of acute health events, including recurrent stroke and bleeding, with lifelong consequences.
Together with the client and leading experts in the field, we developed a robust model to analyse several comparators, risk of recurrent stroke and their impact on health and costs. We stress-tested the model results using alternative input values based on extensive review of the literature and expert opinion.
The model that we co-created with the client worked well and was accepted as a publication in a high-impact academic journal. The publication was downloaded 500 times within the first 3 months. We continue to work closely with the client to help them understand the cost-effectiveness of further iterations of this device and other indications.
Dermatology: overcoming the short-term bias in clinical evidence to compare long-term efficacy of psoriasis treatments
Comparing the effectiveness of treatments for moderate-to-severe plaque psoriasis requires overcoming the following challenges:
(1) Although the majority of patients require long-term treatment, most trials investigate the initial “induction phase” of treatment, during the first 10-16 weeks.
(2) The relatively few studies with long-term evidence during the “maintenance phase” of treatment differ substantially in design (e.g. cross-over, withdrawal, re-treatment) and treatments compared.
We wanted to find a scientifically rigorous way to identify all systemic therapies approved for this indication and to compare their efficacy at one year based on the gold-standard Psoriasis Area and Severity Index (PASI).
Building on our previous work, which we published in a high-impact journal and has been cited over 50 times, we identified, synthesised, and analysed studies published between 2000 and 2018 according to PRISMA guidelines. We comprehensively assessed the studies for heterogeneity that might confound our comparisons. This led us to perform a hierarchical Bayesian network meta-analysis of PASI using an ordered probit model to estimate probabilities that patients would achieve PASI scores of 75, 90 or 100.
Using this thorough review, we arrived at two clarifying discoveries. One was that placebo cross-over after the induction phase turned many studies into essentially one-arm trials. The other was that PASI in the placebo group appeared to plateau in the transition from the induction to maintenance phase of treatment. This led us to propose two analyses, which we validated with leading psoriasis clinicians:
(1) One analysis would compare outcomes at 52 weeks across 9 studies that reported complete placebo and treatment data out to that time point.
(2) A second analysis would assume that placebo response during a maintenance phase would remain the same as during the induction phase. This assumption of a “placebo plateau” allowed us to compare placebo and treatment data out to 52 weeks in a network of 28 studies, instead of 9.
Our work provided a rigorous foundation for our clients to compare their product with all available treatments for moderate-to-severe plaque psoriasis, and these comparisons could support major R&D decisions. The work was subsequently published in three highly ranked journals and presented at a major international meeting. Our work has proven extremely relevant to researchers, clinicians and regulators: the Professional Society for Health Economics and Outcomes Research (ISPOR) commended our approach in 2020, creating an industry-wide precedent for how healthcare stakeholders can overcome evidence gaps that interfere with health economics and outcomes research.
Dermatology: validating comparisons of disease treatments in the absence of head-to-head trials
We believe that good consulting practice means identifying industry needs and seeking to address them. From our long experience in the field of psoriasis, we were aware that most clinical trials for new agents use placebo rather than other agents as the comparator. Thus, most comparisons of treatment efficacy have relied on network meta-analyses (NMAs). Our client and us therefore wondered: what if NMAs were not giving a reliable picture? We wanted to ensure that clinical and regulatory decisions would be based on solid evidence.
Our team systematically searched the literature for NMAs comparing at least two biologics to treat moderate-to-severe psoriasis. We compared the quality, methodology and funding sources across 18 NMAs, and we focused on two clinical outcomes common across the studies. We found that all the NMAs came to similar conclusions despite differences in methodology and sources of funding.
Our work, which supported the validity of NMAs for treatment comparisons in moderate-to-severe psoriasis, led to a publication in a highly ranked journal and a presentation at a global conference. Our client, a company with strong pipeline in skin diseases, were able to use our findings immediately to support major short- and long-term R&D decisions. More broadly, our work has proven extremely relevant to researchers, clinicians and regulators in multiple therapeutic areas where head-to-head treatment comparisons are lacking. Thus, our publication has been accessed more than 1700 times since 2020.
Neurology: evaluating the cost-effectiveness of a medical device
A global medical technology company asked us to assess the cost-effectiveness of their medical device for treating a neurological condition. They wanted to compare the combined use of their device and medicines with the sole use of medicines. The client needed a cost-effectiveness model that could inform future health technology assessments, that was sufficiently flexible to allow internal stakeholders to identify key drivers of cost-effectiveness, and that could evolve to take into account new research findings and additional comparators.
After we thoroughly reviewed the clinical and economic literature, we realised that we would need to be innovative in developing our model in order to robustly synthesise a heterogeneous evidence base. We made use of individual-patient data (IPD), utility mapping and real world evidence (RWE) to inform the model, including bespoke statistical analysis of registry data. Through continuous discussion with the client as well as trusted clinical and economic experts, we developed a user-friendly, highly adjustable cost-effectiveness model that could function robustly for different scenarios and local settings.
After ensuring that the model met the client’s expectations, we helped roll it out to regional stakeholders and lead training sessions to explain its use and suggest how best to apply it to the available evidence. We also performed a stand-alone cost-effectiveness analysis that was accepted for publication in a well-regarded academic journal, given that our work used contemporary estimates of costs, replacement, and discontinuation to estimate the cost-effectiveness of the device in the English NHS setting.
We continue to work closely with the client to support their submission strategies in multiple countries, and we advise them on critical areas for further research and development. We also work with the client and regional stakeholders to adapt the model appropriately as more evidence becomes available.
Oncology: overcoming limited evidence to gain reimbursement for a blockbuster oncology drug
A major global drug manufacturer wished to achieve reimbursement in the UK and the return on investment for its promising drug against breast cancer. Our client faced a challenge, however: abundant evidence showed that their drug slowed cancer progression, but not enough data were available to determine whether the drug improved overall survival. This task was especially difficult because the client was proposing the drug as a first-line treatment, yet patients might use several downstream drugs as their disease progressed, confounding survival outcomes.
To prepare for the reimbursement submission, we completed a gap analysis of the existing evidence and compiled a list of its strengths and weaknesses. We explored multiple methods for linking the progression evidence to patient survival. In the end, we developed a model that drew on the difference in progression between the drug and control arms, as well as data on sequential oncology treatments. We successfully argued that despite the uncertainty due to confounding from the use of multiple medications during progression, the ability of the client’s drug to slow progression suggested a positive impact on patient survival.
We aligned the client’s global executive team and the local market access colleagues behind a submission that ultimately convinced three healthcare payers of the drug’s value (National Institute of Clinical Excellence, Scottish Medicines Consortium and the Irish National Centre for Pharmacoeconomics). As a result, the treatment was made available within the client’s desired pricing strategy – making the drug the first alternative to hormone therapy to become available in the last 10 years to women with breast cancer. Since regulatory agencies did not raise any concerns and no protracted negotiations over pricing were necessary, several thousand patients were able to benefit immediately from the treatment, substantially boosting the client’s market share.
Policy and methods: developing a framework for analysing the impact of patient-centred outcomes for achieving reimbursement in the UK
Patient-centred outcomes (PCOs) focus on a patient’s beliefs, opinions, and needs, and are key to measuring and optimising the global transformation towards patient-centred healthcare. However, to what extent reimbursement agencies take PCOs into account when reviewing health technology assessment (HTA) submissions is unclear. Our client wanted to understand the impact of PCOs on HTAs submitted to the UK National Institute of Health and Care Excellence (NICE). They were particularly interested in the impact of PCOs other than quality of life as measured with the EuroQol-5D (EQ-5D). The answer had important implications for the client’s short- and long-term research and development strategy.
Working together with the client, Symmetron developed a framework to analyse PCO impact in NICE HTAs. The framework included clinical and cost-effectiveness data, as well as barriers and facilitators of PCO impact mentioned by NICE or the manufacturer. We first conducted a pilot study on eight HTAs submitted to NICE and two HTAs submitted to the Scottish Medicines Consortium. We then applied the framework to a larger dataset of 69 publicly available NICE appraisals, of which 42 contained PCOs other than EQ-5D.
Based on our analytical framework, PCO evidence had a substantial impact on NICE decision-making in 13/42 NICE appraisals, most often as part of the economic model.
Our analysis helped the client understand the current impact of PCOs in HTA submissions. These results provide general feedback on how PCO measures may be included in a company submission, which in turn could support a more favourable NICE assessment. Our findings were presented at the Health Technology Assessment International conference in June 2021 (PP42) and have been published in the International Journal of Technology Assessment in Health Care in December 2021.
Rare diseases: gaining reimbursement for a drug targeting a rare disease
Idiopathic pulmonary fibrosis is an increasing health threat, yet its status as a “rare disease” means that research about it is pretty limited. Our client, a major drug manufacturer interested in bringing only the second treatment onto the market, needed our help to develop a robust economic evaluation for reimbursement submissions.
We first conducted a systematic review and network meta-analysis of the literature. We used the data to build a model for the UK National Institute for Health and Care Excellence (NICE), which we subsequently adapted to 10 other health care systems to support the client’s global strategy.
We collaborated with the client through multiple phases of health economic modelling, achieving a level of trust and efficiency that supported a partnership lasting several years. We leveraged our expert knowledge in the disease area and close relationship with the client to develop a global submission strategy.
The client’s regulatory submission to NICE was accepted following its consultation, avoiding months-long revisions and negotiations. As a result, the client’s drug gained rapid market access in the UK and across the globe.
Respiratory: modelling survival after the clinical trials have ended
Progressive fibrotic interstitial lung disease (PF-ILD) was clinically defined relatively recently, and the benefit of treatment for survival has only been studied over 12 months. We knew that a deeper understanding of survival, especially in the long term, would be needed to demonstrate a treatment’s value fully.
Our deep experience with idiopathic pulmonary fibrosis (IPF) and our thorough literature analysis pointed to the hypothesis that the survival of patients with PFI-ILD was likely similar to that of patients with IPF.
We used propensity score matching and combined long term evidence from an IPF cohort with a clinical trial of PF-ILD, using Bayesian survival analysis. This method is highly innovative and exploratory. It was well-received by reviewers and reimbursement agencies, which acknowledged that we were trying to reduce uncertainty in the survival estimates of patients with PF-ILD.
Our survival data remain the most comprehensive estimate of medium- and long-term survival of patients with PF-ILD. It will play a pivotal role in future cost-effectiveness modelling in this disease area.