Budget impact and pharmacy costs with targeted use of oliceridine for postsurgical pain in patients at high risk of opioid-related adverse events

Figures & data

Table 1. Summary of efficacy outcomes, rescue analgesic, and rescue antiemetic medication use in the health economic analysis [8]

Input parameter	Treatment allocation	Value
Efficacy (% Responder)
	Oliceridine 0.35 mg demand dose initial responders	66.1%
	Oliceridine 0.5 mg demand dose incremental proportion of responders	19.4%
	Morphine 1 mg demand dose	73.6%
Rescue analgesic medication Use (%)
	Oliceridine 0.35 mg demand dose	17.0%
	Oliceridine 0.5 mg demand dose	14.5%
	Morphine 1 mg demand dose	12.0%
Rescue antiemetic medication Use (%)
	Oliceridine 0.35 mg demand dose	45.3%
	Oliceridine 0.5 mg demand dose	51.1%
	Morphine 1 mg demand dose	62.9%

The data shown here are obtained from the two randomized placebo- and morphine-controlled Phase 3 studies (pivotal) in patients with moderate to severe acute pain following either orthopedic surgery–bunionectomy (APOLLO-1, Study 1) [9], or plastic surgery–abdominoplasty (APOLLO-2, Study 2) [10]. The pre-specified primary clinical efficacy outcome in the pivotal Phase 3 studies was the categorical outcome of response defined as patients who met the following criteria: 1) at least a 30% improvement in final time-weighted sum of the pain intensity differences (SPID) from baseline at 48 hours (SPID-48) for orthopedic surgery–bunionectomy or at 24 hours (SPID-24) for plastic surgery–abdominoplasty; 2) without use of rescue pain medication during the randomized treatment period; 3) without early discontinuation of study medication for any reason; and 4) without reaching the study medication volume-based dosing limit. Prophylactic antiemetics were not allowed and patients enrolled had a high risk of postoperative nausea and vomiting (PONV), based on their Apfel scores at baseline (≥3) [9,10].

Table 2. Adverse event incidence and risk-ratio computation from pooled pivotal randomized controlled Phase 3 RCTs (orthopedic surgery–bunionectomy study and plastic surgery–abdominoplasty study) [Modified from 8]

Adverse Event	Treatment Allocation
	Oliceridine 0.35 mg demand dose	Oliceridine 0.5 mg demand dose	Morphine 1 mg demand dose
Low O2 Saturation
Value (%)	14.6	17.0	22.2
Risk-ratio applied	1.52	1.16	–
Vomiting
Value (%)	30.3	41.5	51.9
Risk-ratio applied	1.71	1.37	–
Somnolence/Sedation
Value (%)	19.0	15.1	23.5
Risk-ratio applied	1.24	0.8	–

The incidence rates of the 3 opioid-related adverse events (ORAEs): O₂ saturation <90%, vomiting and somnolence (and sedation) shown here are derived from the pooled APOLLO–1 & −2 studies. Risk ratios for oliceridine compared to morphine were then calculated.

RCTs = randomized controlled trials.

Table 3. Estimation of expected adverse event incidence in real-world conditions derived from Phase 3 open-label safety study data [8]

Adverse Event	Treatment Allocation
	Oliceridine 0.35 mg demand dose	Oliceridine 0.5 mg demand dose	Morphine 1 mg demand dose
Low O2 Saturation
Value (%)	13.7%	15.9%	24.2%
Vomiting
Value (%)	10.1%	13.8%	23.7%
Somnolence/Sedation
Value (%)	1.9%	1.5%	2.4%

Data shown for all treatment groups are derived from the pivotal randomized Phase 3 studies (APOLLO-1 and −2 as shown in Table 2) [9,10] and then applied to the AE rates observed in the large multisite Phase 3 open-label safety study (Study 3) [9,10]. This large study was an open-label safety study of oliceridine conducted in 768 patients following a wide range of surgical procedures or non-surgical medical conditions. All patients in the study had at least one medical comorbidity. Almost half of all patients (46%) were obese with a BMI ≥30 kg/m² and 32% were aged 65 years or older. For the model, the ORAE risk ratios were applied to the high-risk patients defined as elderly and obese.

AE = adverse event; BMI = body mass index; ORAE = opioid-related adverse event.

Figure 1. Overview of the economic model methodology [Modified from 8].

The model focused on specific AEs: 1) oxygen desaturation defined as measured oxygen saturation with an SpO₂ <90%; 2) vomiting as a reported MedDRA-coded AE; and 3) somnolence, as a reported MedDRA-coded AE directly measured in the Phase 3 studies. Estimates of the risks (risk ratios) of these AE outcomes were derived directly from the safety data measures reported in the Phase 3 orthopedic surgery–bunionectomy (APOLLO-1) [9,10] and plastic surgery plastic surgery–abdominoplasty abdominoplasty (APOLLO-2) [9,10] studies. The risk ratios were then applied to AE rates observed in high-risk patients (age ≥65 years a BMI ≥30 kg/m²) from the Phase 3 open-label safety study of oliceridine [9,10] to estimate the rates of AEs reported among a medically complex, real-world patient sample. Other model parameters are derived from the published literature and observational costs data.AE = adverse event; BMI = body mass index; MedRA = Medical Dictionary for Regulatory Activities; SpO₂ = peripheral oxygen saturation.

Figure 2. Analysis framework for budget impact model. The Budget Impact Model assumes that only high-risk patients (age ≥65 years who have a BMI ≥30 kg/m²) will receive oliceridine and that the balance of lower risk patients in that allocated group will be treated with morphine. Based on the population demographics directly observed in the ATHENA study population [9,10], this subset of higher risk patients is estimated to represent 16.6% of the overall population studied. The Budget Impact Model also assumes a total annual sample of 1,132 eligible surgeries per year, with a distribution of surgical cases as observed on average for hospitals in Florida in 2017 [18]. The Budget Impact Model estimated the total cost for pain medication, the total number of adverse outcomes, and the total number of adverse outcomes averted by using oliceridine for the high-risk patients and morphine for all others, compared to having used only morphine for all patients. A return on investment (ROI) is calculated as the ratio of the total cost of AEs averted divided by the total additional cost of pain medications.AE = adverse event; BMI = body mass index; CABG = coronary artery bypass graft.

Figure 3. Summary of the analytic framework and methodology used to design the oliceridine health economic model [8]. The analytic framework for the overall economic model was structured as a decision tree with two major branches representing treatment with oliceridine or morphine over a 24-hour time period. Treatment response parameters were derived from pooled data from the Phase 3 orthopedic surgery–bunionectomy and Phase 3 plastic surgery–abdominoplasty studies. Risk ratios for oliceridine versus morphine adverse events (AEs) were derived from these pivotal randomized Phase 3 studies and applied to the mean AE rates observed in the ATHENA observational study. This approach was used to prevent the model from using the excessively high rates observed for both treatments in the pivotal Phase 3 trials due to protocol specifications that did not permit the use of multimodal analgesia. Failure of oliceridine 0.35 mg dosing was assumed to lead to escalation of dosing to oliceridine 0.5 mg, and to use of rescue analgesic medication if patients failed this higher dose. Failure of the morphine medication was assumed to lead directly to use of rescue analgesic medication, as used in the trials. Costs of pain medication, rescue therapy and antiemetic drugs were tabulated based on rates observed in the pivotal Phase 3 studies. The decision tree was ‘rolled back’ and population numbers for each condition were calculated. Standard cost weights for AEs were estimated for each arm of the decision tree.ROI = return on investment; RR = risk ratio.

Table 4. High-risk model: inputs and estimates for the comparative cost of care for 1,000 surgical patients treated on-demand with either oliceridine or morphine

	Oliceridine [0.35 mg with escalation to 0.5 mg for nonresponse] (N = 1,000)	Morphine 1 mg (N = 1,000)	Difference (Oliceridine – morphine)
Cost of pain medication for 24 hours/patient	$108.14	$15.00	($93.14)
Response rate (%)	66.1%	73.6%	(7.5%)
% Escalated to 0.5 mg	19.4%	N/A	N/A
Total number of AEs	309	509	(200)
Respiratory depression (Low O2 saturation)	157	242	(85)
Vomiting	128	237	(109)
Somnolence	24	30	(6)
Cost of pain medication	$127,181	$30,558	$96,623
Cost of AEs	$778,764	$1,238,259	($459,495)
Total Cost	$907,115	$1,271,059	($363,944)

The model results shown here are based on an assumed average daily cost of oliceridine of $100.

The total cost also includes the cost of antiemetics: $1,170 in the oliceridine arm and $2,242 in the morphine arm.

AE = adverse event.

Table 5. Budget impact model: inputs and estimates for the comparative cost of care among 1,132 surgical patients treated on-demand with Policy B (blended use of oliceridine and morphine) compared to Policy A (use of morphine only)

	Treatment Policy A [Use of Morphine Only] (N = 1,132)	Treatment Policy B [Blended Use of Oliceridine and Morphine] (N = 1,132)	Difference* (Policy A – Policy B)
% Population at higher risk of adverse outcomes	16.6%	16.6%	NA
Adverse outcomes
Vomiting	269	237	31
O2 desaturation	166	140	26
Somnolence	27	24	3
Total number of adverse outcomes	461	401	60
Total cost of pain medication	$34,591	$52,748	$18,157
Total cost of adverse outcomes	$964,950	$824,699	($140,251)
Total Cost of Care	$1,002,079	$879,784	($122,296)
Return on Investment			7.7

Policy B utilized blended use of oliceridine for higher-risk patients and morphine for all other low-risk patients.

For results shown here, the cost of oliceridine was set at $100 per day and morphine at $15 per day. The total cost also includes the cost of antiemetics: $1,170 in the oliceridine arm and $2,242 in the morphine arm.

*Any sum differences are due to rounding.

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