Pharmaceutical companies need to replace dose reduction measures with direct toxicity measurement in health-economic models
Dose reduction overlooks the hidden healthcare costs of steroid-toxicity. For HEOR (health economics and outcomes research) evidence teams developing steroid-sparing narratives, this measurement gap undermines cost analyses and weakens payer value propositions. A retrospective analysis of myasthenia gravis demonstrates why direct toxicity measurement through GTI-MD is becoming the new standard for HEOR.
From intuition to evidence
Albert Whangbo, PhD, who leads the global Evidence Generation practice at ZS Associates, captures the transformation underway in pharmaceutical HEOR:
"Using the GTI-MD, we could turn what clinicians intuitively know about steroid-toxicity into quantifiable evidence – and we did it with data that were already sitting in EHRs."
The challenge Whangbo describes is one every pharmaceutical HEOR team developing steroid-sparing therapies confronts: everyone knows steroids cause harm, yet quantifying that harm for economic modeling has remained elusive. Dose serves as a poor surrogate. Individual susceptibility varies. Attribution becomes murky in poly-treated populations. Health-economic models built on dose reduction assumptions miss the actual complications driving costs.
This measurement gap creates three liabilities for pharmaceutical development teams: weak differentiation in crowded therapeutic markets, incomplete benefit-risk profiles that entangle disease burden with treatment burden, and fragile payer positioning that asserts value indirectly through dose metrics rather than demonstrating it directly through measured harm.
The proof of concept
The retrospective analysis of myasthenia gravis (MG) patients published at ISPOR 2024 provides the validation pharmaceutical HEOR teams need. Using the Optum® Market Clarity EHR database, the analysis examined 682 adult MG patients: 377 steroid initiators matched with 305 steroid-naïve controls.
The GTI-MD quantified toxicity across four metabolic domains, captured directly from routine clinical data: BMI, blood pressure, glucose tolerance, and lipid metabolism. Results revealed significantly elevated toxicity scores in steroid initiators, with BMI showing the greatest differential worsening. A greater proportion of steroid initiators exceeded minimal clinically important difference thresholds, demonstrating clinically meaningful toxicity burden attributable to glucocorticoid exposure rather than disease progression.
The methodology's advantages are substantial. Results delivered in months rather than years. Large, diverse patient populations accessed across real-world practice settings. Cost at a fraction of conventional observational study investment. No patient assessment burden.
Whangbo emphasizes the practical implications:
"The GTI-MD allowed us to take what many already know about steroid harms, often anecdotally, and translate that into sensitive, quantitative insights using widely available clinical data. Even with a reduced set of domains, we were able to detect meaningful toxicity changes over relatively short timeframes."
Why pharmaceutical HEOR teams are adopting direct toxicity measurement
Glenn Philips, PhD, Vice President of Health Economics and Outcomes Research at Argenx, explains the strategic imperative driving this shift:
"We're using the same tools that demonstrate the benefit of our drugs to show that the long-term cost of steroids has been vastly underestimated."
The problem Philips identifies extends beyond measurement methodology. It's a market access challenge. Payers perceive steroids as essentially free. Short-term efficacy is established. Upfront costs of novel steroid-sparing therapies create hurdles. Without validated toxicity measurement, cost-effectiveness narratives collapse into dose-reduction claims that fail to quantify actual avoided complications.
Philips describes Argenx's response:
"Getting a handle on the negative costs of steroids has been so hard that, at Argenx, we decided patients couldn't wait for payers and regulators and that we needed to do this for them ourselves."
The insight is strategic: pharmaceutical companies cannot wait for systemic change. HEOR teams must build the evidence themselves. Direct toxicity measurement provides that capability.
Whangbo acknowledges the payer challenge remains:
"Steroids are cheap and effective in the short term. Convincing payers that steroid-sparing therapies are worth the upfront cost is still a practical challenge."
Yet he sees the path forward:
"The GTI-MD is a bridge that gets us part of the way. Decision-makers still want the link to hard outcomes: future costs, hospitalizations, quality-of-life."
Applications across the pharmaceutical development cycle
Direct toxicity measurement through GTI-MD enables specific applications across development stages:
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Target Product Profile Definition: Define measurable steroid-toxicity outcomes for health-economic value propositions aligned with payer priorities. Replace dose reduction targets with validated toxicity burden thresholds.
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Clinical Trial Integration: Add GTI-MD as a structured endpoint to complement traditional efficacy measures. Enable prospective toxicity measurement to support cost-effectiveness modeling. Support patient stratification and enrichment approaches that incorporate baseline toxicity burden.
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Post-Approval HEOR: Execute retrospective EHR analyses to demonstrate real-world toxicity reduction and economic impact. Enable population health management insights for formulary and market access strategies. Build longitudinal evidence linking toxicity prevention to avoided complications and utilization.
The analytical infrastructure already exists
Whangbo emphasizes a critical point:
"There's an enormous opportunity to keep building the bridge from toxicity metrics to patient outcomes and economic consequences. The data exists. The analytical tools are here. What's needed now is collective will and storytelling."
The GTI-MD leverages data routinely captured in EHRs. No novel data collection infrastructure required. Existing real-world data partnerships enable rapid evidence generation. The methodology is validated and disease-agnostic, enabling consistent measurement across therapeutic areas and mechanisms of action.
For pharmaceutical HEOR teams, this represents a strategic advantage: differentiation through standardized toxicity measurement, cost-effectiveness demonstrated with validated clinical endpoints, and payer value propositions supported by direct evidence of harm prevention rather than dose-reduction surrogates.
What this means for pharmaceutical development strategy
The shift from dose reduction to direct toxicity measurement reflects a broader evolution in pharmaceutical HEOR. As steroid-sparing therapies proliferate across therapeutic areas, differentiation requires more than exposure reduction claims. Payers demand evidence linking therapeutic interventions to avoided complications and reduced utilization.
Pharmaceutical HEOR teams equipped with the GTI-MD now have the tools and methodologies to build that evidence at scale, with speed, and at a fraction of the cost of conventional approaches.
The question is no longer whether direct toxicity measurement is feasible. The myasthenia gravis analysis settles that question. The question is which pharmaceutical development teams will adopt this approach to strengthen their health-economic narratives before their competitors do.
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