Dermatology: overcoming the short-term bias in clinical evidence to compare long-term efficacy of psoriasis treatments

The challenge
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).

The approach
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.

The outcome
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 

The challenge
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). We 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.

The approach
We 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.

The outcome
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 clients with a 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 1000 times since 2020.

Oncology: overcoming limited evidence to gain reimbursement for a blockbuster oncology drug

The challenge
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.

The approach
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.

The outcome
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.