Abstract

Background Pain after traumatic injury is common, yet few patients receive adequate pain relief. NHS paramedics have a limited formulary to treat severe pain.

Objectives To estimate the cost-effectiveness of ketamine versus morphine for severe pain in acute traumatic injury.

Methods A cost-utility analysis was conducted based on data from a pragmatic, multicentre, randomised controlled trial (PACKMAN). The base-case analysis took the form of an intention-to-treat analysis conducted from a UK National Health Service (NHS) and personal social services (PSS) perspective and separately from a societal perspective. Costs (£ 2021–2022 prices) were collected prospectively over a 6-month follow-up period. A bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted to estimate the incremental cost per QALY gained and the incremental net monetary benefit (INMB) of ketamine in comparison to morphine. Sensitivity and pre-specified subgroup analyses explored uncertainty and heterogeneity in cost-effectiveness estimates.

Results Participants (n=416) were randomised to ketamine (n=206) or morphine (n=210) amongst whom complete data for the economic evaluation was available for 189 (45.4%) participants. Mean (standard deviation [SD]) observed NHS and PSS costs over 6 months were £5,191 (£3,155) in the ketamine arm versus £5,143 (£3,897) in the morphine arm (mean difference [MD]: £47, p=0.926). Mean (SD) observed QALY estimates were 0.309 (0.10) versus 0.293 (0.010), respectively (MD: 0.016, p=0.273).

The base case (imputed) analysis generated an incremental cost of −£117 (95%CI: −£849 to £597) and incremental QALYs of 0.025 (95%CI: 0.010 to 0.041), indicating a 92%-96% probability of cost-effectiveness at cost-effectiveness thresholds of £20,000 and £30,000 per QALY. A sensitivity analysis, using observed data only (without imputation) generated an incremental cost of £233 (95%CI: −£783 to £1216) and incremental QALYs of 0.016 (95%CI: −0.013 to 0.044), indicating a lower 54%-62% probability of cost-effectiveness. The base-cost cost-effectiveness results remained robust to other sensitivity analyses.

Conclusions This economic evaluation found that ketamine administered by paramedics to adults with severe pain following traumatic injuries is cost-effective compared to morphine. However, our results are subject to high levels of missing data, which were handled through recommended multiple imputation techniques.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

ISRCTN14124474

Funding Statement

The PACKMaN trial was funded by the National Institute for Health and Care Research Health Technology Assessment Programme (HTA NIHR128086).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics approval for the PACKMAN trial was given by West of Scotland Research Ethics Committee (REC number 16/LO/0349) on 01/09/2020.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

List of abbreviationsCCPsCritical care paramedicsCIConfidence intervalsCNSCentral nervous systemFMIFraction of missing informationGSEMGeneralized structural equation modellingHRQoLHealth-related quality of lifeICERIncremental cost-effectiveness ratioIMPInvestigational medicinal productINMBIncremental net monetary benefitIOIntraosseousIVIntravenousMARMissing at randomMCMCMarkov chain Monte CarloMDMean differenceMNARMissing not-at-randomNHSNational health serviceNHSBSANational Health Service Business Service AuthorityNHSCIINHS Cost Inflation IndexNICENational Institute for Health and Care ExcellenceNRSNumeric rating scaleOROdd ratioPACKMANParamedic Analgesia Comparing Ketamine and MorphiNePCAPrescription Cost AnalysisPSSPersonal social servicesPSSRUPersonal social services research unitPTSDPost-traumatic stress disorderQALYQuality-adjusted life-yearRCTRandomised controlled trialSDStandard deviationSPIDSum of Pain Intensity DifferenceSURSeemingly unrelated regressionWMASWest midland ambulance serviceYASYorkshire ambulance service