The potential price and access implications of the cost-utility and budget impact methodologies applied by NICE in England and ICER in the US for a novel gene therapy in Parkinson’s disease

Figures & data

Table 1. Examples of value-based assessment tools available in the USA.

Value framework	Description
American College of Cardiology (ACC) and the American Heart Association (AHA) [14]	Year of introduction/publication: 2014ACC and AHA are now assessing value for money by CUA (i.e. cost per Quality-Adjusted Life Year [QALY]) in their clinical guidelines to complement their recommendations The threshold values used by ACC/AHA for determining what is an acceptable cost per additional QALY are informed by the World Health Organization’s (WHO) benchmark of three times the Gross Domestic Product (GDP): <$50k = high value; $50k-$150k = intermediate value; >$150k = low value
Premera Blue Cross (private health insurance in Washington state and Alaska) [15]	Year of introduction/publication: 2010 Uses a CUA with cost per QALY thresholds similar to the ACC/AHA to allocate drugs to formulary tiers (<$10k = tier 1; <$50k = tier 2; $50k-$150k = tier 3; >$150k = tier 4)
Drug Abacus [13,65]	Year of introduction/publication: 2015 An interactive online tool, developed specifically for cancer treatments, to help patients and providers compare the value for money of different cancer therapies based on their own customised preferences and value definitions The tool allows users to define the values for a year of life, discount for toxicities, multiplier for novel mechanism of action or rarity of disease, unmet need and more, and compares different cancer drugs’ performance according to these user-defined metrics
American Society of Clinical Oncology (ASCO) value framework [65,66]	Year of introduction/publication: 2015 Assesses the value of new cancer therapies based on clinical benefit, side effects, and improvements in patient symptoms or quality of life in (termed the Net Health Benefit) in the context of costs incurred by the patient (e.g. patient co-payments) It includes no threshold values for cost vs. benefit, and it is up to the patient to decide what constitutes higher or lower value
National Comprehensive Cancer Network’s (NCCN) Evidence Blocks [12,65]	Year of introduction/publication: 2015Assesses efficacy, safety, affordability, quality and consistency of evidence from 1 (least favourable) to 5 (most favourable) Does not have any threshold values for higher/lower value, and uses only the one-to-five scale to signify level of cost (rather than actual costs in dollars)
The Institute for Clinical and Economic Review (ICER) [19]	Year of introduction/publication: 2015Assesses long-term value and short-term affordability, including cost-effectiveness and budget impact to support evidence-based decisions Uses a CUA with cost per QALY thresholds similar to the WHO-definition: <$50k = high value; $50k-$175k = intermediate value; >$175k = lower value (in ultra-rare indications, a cost/QALY of >$175k can be accepted) Also assesses affordability through budget impact analyses

Table 2. ‘Contextual considerations’ and ‘Other Benefits or Disadvantages’ as considered in ICER’s value assessment framework.

Contextual Considerations	Other Benefits or Disadvantages
The intervention is intended for the care of individuals with a condition of particularly high severity in terms of impact on length of life and/or quality of life	The intervention provides significant direct patient health benefits that are not adequately captured by the QALY
The intervention is intended for the care of individuals with a condition that represents a particularly high lifetime burden of illness	The intervention offers reduced complexity that will significantly improve patient outcomes
The intervention is the first to offer any improvement for patients with this condition	The intervention will reduce important health disparities across racial, ethnic, gender, socioeconomic, or regional categories
There is significant uncertainty about the long-term risk of serious side effects of this intervention*	The intervention will significantly reduce caregiver or broader family burden
There is significant uncertainty about the magnitude or durability of the long-term benefits of this intervention*	The intervention offers a novel mechanism of action or approach that will allow successful treatment of many patients who have failed other available treatments
There are additional contextual considerations that should have an important role in judgments of the value of this intervention (not specified in the above)	The intervention will have a significant impact on improving return to work and/or overall productivity
	There are other important benefits or disadvantages that should have an important role in judgments of the value of this intervention (not specified above)

* When compared to the comparator therapy

Figure 1. Threshold values used for cost per incremental QALY in ICER’s value assessment framework.

Table 3. Key features of the Markov model used.

Model feature	Detail
Cycle length	Six months
Time horizon	Lifetime
Discount rate	3.5% for both costs and QALYs
Perspective	Healthcare system

Figure 2. Health states and transitions in the health economic model.

‘OFF’1: 0–25% of waking hours spent in ‘off’ state‘OFF’2: 25–50% of waking hours spent in ‘off’ state‘OFF’3: 50–75% of waking hours spent in ‘off’ state‘OFF’4: > 75% of waking hours spent in ‘off’ state

Table 4. Patient baseline and efficacy scenarios.

Baseline			Efficacy scenarios
H&Y score	‘Off’ state	Age	Symptomatic effect (partial response)	Disease-modifying effect (optimal response)
3	> 75% ‘off’ time	63*	H&Y score 3 < 25% ‘off’ time	H&Y score 2 < 25% ‘off’ time

* Informed by Zhao et al. (2010) [67]

Figure 3. Graphical illustration of the (UK) costs and disutilities associated with the health states in the model (except death²).

Figure 4. Comparison of estimated maximum cost-effective prices for the gene therapy in the US and England, for patients with H&Y3 and > 75% ‘OFF’ time at baseline (assuming five years duration of effect).

* English results are adjusted for the average £-to-$ exchange rate for 2017 (1.29) [68] to allow the comparison (original results shown in GBP in parentheses)

Figure 5. Maximum number of English patients eligible for treatment in year one according to the max prices identified* for patients with H&Y3/’OFF’4 at baseline and the £20-million budget impact threshold.

* £198,556 per patient for partial response; £250,264 per patient for optimal response** £39,711 per patient (£198,556/5 years) for partial response; £50,053 per patient (£250,264/5 years) for optimal response*** Over five years^ Maximum number of patients in years one through five (as the annuity payments are split over five years)

Figure 6. Maximum number of US patients eligible for treatment in year one according to the max prices identified* for patients with H&Y3/’OFF’4 at baseline and the $457.5-million budget impact threshold.

* $448,662 per patient for partial response; $591,662 per patient for optimal response** $ 89,732 per patient ($448,662/5 years) for partial response; $118,332 per patient ($591,662/5 years) for optimal response*** Over five years^ Maximum number of patients in years one through five (as annuity payments are split over five years)

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