On the March 2, 2021, the Institute for Clinical and Economic Review (ICER) released its final evidence report on three emerging treatments for high cholesterol patients: inclisiran (Novartis), bempedoic acid and bempedoic acid/ezetimibe (Esperion Therapeutics). Not surprisingly, the report made several unsupported recommendations with regard to pricing and product access.

Most notably, the report uses a modeled simulation of the high cholesterol patient population to conclude that any quality adjusted life years (QALYs) gained by switching to these new therapies would be minimal. Specifically, the report assigns these treatments the following QALY gains versus comparable existing treatments:

  • 0.44 discounted QALYs – or 5.28 months — for inclisiran from Novartis
  • 0.17 discounted QALYs – or 2.04 months – for bempodic acid from Esperion Therapeutics

Using its assumption-driven simulations, ICER claims to have determined the health benefit price benchmark (HBPB) for these treatments. According to ICER’s website, the HBPB is: “the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.”

In other words, ICER claims that its models, which once again include no data collected from actual patients, can accurately determine the appropriate price for new treatments and their overall value to the health care system. For the treatments in this report, ICER assigned the following HBPB ranges for the eligible patient populations:

  • $1,600 to $2,600 for bempedoic acid/ezetimibe
  • $3,600 to $6,000 for inclisiran

There are numerous problems with both the QALY and HBPB estimates in the report.

First, neither of these conclusions are based on measured differences in benefits among actual patients. Instead, they are centered around a generic utility score evaluating the disease progression of a group of hypothetical patients.

More specifically, the QALY conclusions are based on scoring measurements that are not only scientifically flawed, but mathematically impossible. From Dr. Paul Langley, of the University of Minnesota College of Pharmacy:

It should be noted that the QALYs utilized in this report and the earlier ICER final evidence report on PCSK9 inhibitors are not created from multi-attribute utility instruments such as the EQ-5D-3L. Rather, they are ‘created’ from disability weight estimates from the Global Burden of Disease Study where 0 = perfect health (no disability noted) to 1 = death (or close to it). The disability weights, which are on an entirely different conceptual basis from multi-attribute utilities (where 0 = perfect health and 0 = death) ICER was asked how they justified the use of disability weights. In response the claim was that a QALY = 1 – DALY (i.e., you reverse the DALY estimate). This is quite misleading. What they should have said was that a utility = 1 – disability weight (by assumption). This is unacceptable given the different conceptual basis for these measures. Further, the disability weight suffers from the same fatal flaw as a utility: it is an ordinal score. It is impossible to subtract one ordinal score from another (unless you ignore the axioms of fundamental measurement). You cannot subtract a DALY estimate from 12 months and create an ‘ersatz’ QALY as the DALY is mathematically meaningless, although 12 months are on a ratio scale. The same objection applies to the ‘ersatz’ QALYs used in the previous ICER report on PCSK9 inhibitors for high cholesterol which rely on disability weights.

With the HBPB estimates, ICER claims to have determined – with startling precision – the proper amount to “reward” drug companies for their innovation on these high cholesterol treatments. However, on top of the impossible math used to reach these calculations, ICER’s pricing determination includes little, if any, information on the drugs’ value for real, flesh-and-blood patients. That is strange for a model that supposedly measures a drug’s impact on patients’ quality of life.

ICER is undoubtedly aware of the existence of mathematical instruments that can better measure and evaluate quality of life and the fulfillment of patient needs. Many of them are disease specific. And, while these tools may not always provide a complete account of a drug’s impact, they can provide a far more meaningful estimate of the value of new therapies for patients.

Further, ICER’s estimated price ranges give no apparent consideration as to what pricing levels would encourage future investments and innovation in this class of therapeutics. In addition, the report measures the new treatments’ values against the prices of two existing PCSK9 inhibitors — Repatha (Amgen) and Praluent (Regeneron). Yet, the set prices for both these drugs reflect substantial discounts, largely driven by previous ICER recommendations. This makes them less reliable as price reference points for newly developed treatments.

All these considerations – and several others – would factor heavily into everyday pricing negotiations between drug companies, insurers, and providers. Yet, ICER purports to have determined the proper price range for these new treatments without them.

Given the questionable ethics and the likelihood of discrimination against chronically ill, disabled, or elderly patients, any pricing or value inferences based on QALY-centric models are inherently suspect. And, as we have documented many times in this space, ICER’s QALY models virtually always fail to meet even the most basic thresholds for credible scientific inquiry or analysis.

The latest evidence report on these new high-cholesterol treatments is another prime example of these failings in ICER’s methodology and approach. As a result, no one making any pricing or coverage decisions regarding these drugs should take the report at face value.