Responsiveness of multiple patient-reported outcome measures for acute postsurgical pain: primary results from the international multi-centre PROMPT NIT-1 study.

BACKGROUND: Postsurgical outcome measures are crucial to define the efficacy of perioperative pain management; however, it is unclear which are most appropriate. We conducted a prospective study aiming to assess sensitivity-to-change of patient-reported outcome measures assessing the core outcome set of domains pain intensity (at rest/during activity), physical function, adverse events, and self-efficacy. METHODS: Patient-reported outcome measures were assessed preoperatively, on day 1 (d1), d3, and d7 after four surgical procedures (total knee replacement, breast surgery, endometriosis-related surgery, and sternotomy). Primary outcomes were sensitivity-to-change of patient-reported outcome measures analysed by correlating their changes (d1-d3) with patients' global impression of change and patients' specific impression of change items as anchor criteria. Secondary outcomes included identification of baseline and patient characteristic variables explaining variance in change for each of the scales and descriptive analysis of various patient-reported outcome measures from different domains and after different surgeries. RESULTS: Of 3322 patients included (18 hospitals, 10 countries), data from 2661 patients were analysed. All patient-reported outcome measures improved on average over time; the median calculated sensitivity-to-change for all patient-reported outcome measures (overall surgeries) was 0.22 (range: 0.07-0.31, scale: 0-10); all changes were independent of baseline data or patient characteristics and similar between different procedures. CONCLUSIONS: Pain-related patient-reported outcome measures have low to moderate sensitivity-to-change; those showing higher sensitivity-to-change from the same domain should be considered for inclusion in a core outcome set of patient-reported outcome measures to assess the effectiveness and efficacy of perioperative pain management.

Assessment of Patient-Reported Outcome Instruments to Assess Chronic Low Back Pain.

Objective: To identify patient-reported outcome (PRO) instruments that assess chronic low back pain (cLBP) symptoms (specifically pain qualities) and/or impacts for potential use in cLBP clinical trials to demonstrate treatment benefit and support labeling claims. Design: Literature review of existing PRO measures. Methods: Publications detailing existing PRO measures for cLBP were identified, reviewed, and summarized. As recommended by the US Food & Drug Administration (FDA) PRO development guidance, standard measurement characteristics were reviewed, including development history, psychometric properties (validity and reliability), ability to detect change, and interpretation of observed changes. Results: Thirteen instruments were selected and reviewed: Low Back Pain Bothersomeness Scale, Neuropathic Pain Symptom Inventory, PainDETECT, Pain Quality Assessment Scale Revised, Revised Short Form McGill Pain Questionnaire, Low Back Pain Impact Questionnaire, Oswestry Disability Index, Pain Disability Index, Roland-Morris Disability Questionnaire, Brief Pain Inventory and Brief Pain Inventory Short Form, Musculoskeletal Outcomes Data Evaluation and Management System Spine Module, Orebro Musculoskeletal Pain Questionnaire, and the West Haven-Yale Multidimensional Pain Inventory Interference Scale. The instruments varied in the aspects of pain and/or impacts that they assessed, and none of the instruments fulfilled all criteria for use in clinical trials to support labeling claims based on recommendations outlined in the FDA PRO guidance. Conclusions: There is an unmet need for a validated PRO instrument to evaluate cLBP-related symptoms and impacts for use in clinical trials.

Epidemiology and treatment of pain associated with osteoarthritis of the knee in Germany: A retrospective health claims data analysis.

Objective: Osteoarthritis of the knee (knee OA) is a serious joint disease leading to pain and reduced quality of life. Pharmacological treatments include anti-inflammatories, analgesics, intraarticular hyaluronic acid, and intraarticular corticosteroids while for severe knee OA, knee replacement is an option. This study examined the incidence, prevalence, patient characteristics, and uptake of medical and surgical treatments in knee OA patients in Germany. Design: A non-interventional, retrospective health claims data analysis with anonymized data from the InGef database was performed. Patients ≥18 years were analyzed cross-sectionally for each year 2015-2020. Newly diagnosed patients in 2015 were also longitudinally analyzed until end of 2020. Results: Annual knee OA prevalence increased from 7.07 â€‹% in 2015 to 7.39 â€‹% in 2020. Annual incidence proportions ranged from 1.71 â€‹% in 2015 to 1.46 â€‹% in 2020. Knee replacement was the most common surgery, with rising patient numbers (e.g., 7918 patients in 2015 and 8975 patients in 2019). Approximately 62 â€‹% of patients newly diagnosed in 2015 received prescription pharmacological pain treatment during follow-up. Most (96.95 â€‹%) received non-opioid analgesics, followed by weak opioids (8.14 â€‹%) and strong opioids (3.00 â€‹%) as first-line treatment (combinations possible). Knee surgery was performed in 16.6 â€‹% of patients during follow-up. Median time from first diagnosis until surgery was 346 days for any knee surgery and 564 days for knee replacement. Conclusions: The number of patients with knee OA in Germany is steadily rising, along with an increasing number of surgical interventions, especially knee replacement. Time until first surgery and knee replacement is relatively short, even for newly diagnosed patients.

Validity and responsiveness of EuroQol-5 dimension (EQ-5D) versus Short Form-6 dimension (SF-6D) questionnaire in chronic pain.

BACKGROUND: Assessments of health-related quality of life and particularly utility values are important components of health economic analyses. Several instruments have been developed to measure utilities. However no consensus has emerged regarding the most appropriate instrument within a therapeutic area such as chronic pain. The study compared two instruments - EQ-5D and SF-6D - for their performance and validity in patients with chronic pain. METHODS: Pooled data from three randomised, controlled clinical trials with two active treatment groups were used. The included patients suffered from osteoarthritis knee pain or low back pain. Differences between the utility measures were compared in terms of mean values at baseline and endpoint, Bland-Altman analysis, correlation between the dimensions, construct validity, and responsiveness. RESULTS: The analysis included 1977 patients, most with severe pain on the Numeric Rating Scale. The EQ-5D showed a greater mean change from baseline to endpoint compared with the SF-6D (0.43 to 0.58 versus 0.59 to 0.64). Bland-Altman analysis suggested the difference between two measures depended on the health status of a patient. Spearmans rank correlation showed moderate correlation between EQ-5D and SF-6D dimensions. Construct validity showed both instruments could differentiate between patient subgroups with different severities of adverse events and analgesic efficacies but larger differences were detected with the EQ-5D. Similarly, when anchoring the measures to a disease-specific questionnaire - Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) - both questionnaires could differentiate between WOMAC severity levels but the EQ-5D showed greater differences. Responsiveness was also higher with the EQ-5D and for the subgroups in which improvements in health status were expected or when WOMAC severity level was reduced the improvements with EQ-5D were higher than with SF-6D. CONCLUSIONS: This analysis showed that the mean EQ-5D scores were lower than mean SF-6D scores in patients with chronic pain. EQ-5D seemed to have higher construct validity and responsiveness in these patients.

Patient Reported Outcome Measures in Chronic Neuropathic Pain Clinical Trials - A Systematic Literature Review.

In neuropathic pain clinical trials, the patient's perspective is often insufficiently reflected focusing mainly on pain intensity. Comparability of outcome assessment is limited due to heterogenous patient reported outcome measures (PROMs). The MEDLINE, CENTRAL, and Embase databases and reference lists of published meta-analyses were searched. Randomized controlled studies assessing treatment efficacy of drugs for chronic neuropathic pain were included. PROMs were assigned to recommended IMMPACT/NeuPSIG domains: pain intensity, pain other aspects, physical functioning, emotional functioning, global improvement and satisfaction, adverse events, participant disposition. Domains and PROMs were compared regarding the publication year and methodological quality of the studies. Within the 251 included studies 200 PROMs were used with 27 being recommended by IMMPACT/NeuPSIG. The number of domains was higher in high/moderate quality studies. The (sub-) domains 'physical functioning', 'global improvement and satisfaction', and 'neuropathic pain quality' were assessed more frequently in high/moderate quality studies and those published after 2011. Recent studies and those of better quality more often used the recommended PROMs. Although neuropathic assessment via PROMs has improved, there is still a high heterogeneity. A standardized core set of outcome domains and should be defined to improve neuropathic pain treatment and to achieve better comparability of clinical trials. Perspective: This systematic literature review assesses the use of patient reported outcome measures (PROMs) in chronic neuropathic pain. The results show that there is still a high heterogeneity, highlighting the need for a standardized core set of outcome domains and PROMs to improve comparability of clinical trials and neuropathic pain treatment.

Developing consensus on core outcome sets of domains for acute, the transition from acute to chronic, recurrent/episodic, and chronic pain: results of the INTEGRATE-pain Delphi process.

Background: Pain is the leading cause of disability worldwide among adults and effective treatment options remain elusive. Data harmonization efforts, such as through core outcome sets (COS), could improve care by highlighting cross-cutting pain mechanisms and treatments. Existing pain-related COS often focus on specific conditions, which can hamper data harmonization across various pain states. Methods: Our objective was to develop four overarching COS of domains/subdomains (i.e., what to measure) that transcend pain conditions within different pain categories. We hosted a meeting to assess the need for these four COS in pain research and clinical practice. Potential COS domains/subdomains were identified via a systematic literature review (SLR), meeting attendees, and Delphi participants. We conducted an online, three step Delphi process to reach a consensus on domains to be included in the four final COS. Survey respondents were identified from the SLR and pain-related social networks, including multidisciplinary health care professionals, researchers, and people with lived experience (PWLE) of pain. Advisory boards consisting of COS experts and PWLE provided advice throughout the process. Findings: Domains in final COS were generally related to aspects of pain, quality of life, and physical function/activity limitations, with some differences among pain categories. This effort was the first to generate four separate, overarching COS to encourage international data harmonization within and across different pain categories. Interpretation: The adoption of the COS in research and clinical practice will facilitate comparisons and data integration around the world and across pain studies to optimize resources, expedite therapeutic discovery, and improve pain care. Funding: Innovative Medicines Initiative 2 Join Undertaking; European Union Horizon 2020 research innovation program, European Federation of Pharmaceutical Industries and Associations (EFPIA) provided funding for IMI-PainCare. RDT acknowledges grants from Esteve and TEVA.

Stated preferences of physicians and chronic pain sufferers in the use of classic strong opioids.

We conducted a two-stage study in France, Germany, Italy, Spain, Sweden, and the United Kingdom of the stated preferences of chronic pain sufferers treated with classic strong opioids and of physicians treating such patients. The qualitative stage identified attributes perceived important through focus groups with 84 pain sufferers and semistructured interviews with 11 physicians. The quantitative stage included online, discrete choice experiments (DCEs) in which respondents chose between hypothetical profiles or an opt-out in 15 choice tasks. The profile descriptions were based on the attributes elicited in the qualitative stage. DCEs were conducted for pain sufferers (N = 242) and physicians (N = 270) who passed a rationality test. Main-effects models were estimated by hierarchical Bayesian regression. Sufferers ranked nausea, pain impact, energy, alertness, and constipation; physicians ranked pain response, central nervous system (CNS) effects, nausea, dose form, and constipation in descending order of importance. Sufferers were unwilling to incur severe side effects to decrease pain and chose the opt-out in approximately one half of the choice tasks, whereas physicians were willing to trade between profiles. The models predicted physicians' choices better than those of pain sufferers. No age, sex, or country effects were seen, but stronger preferences were found among physicians treating noncancer (n = 40) than cancer pain and among the 55% of sufferers who had never discontinued long-term pain medication use. Sufferers' mean pain scores on an 11-point Likert scale were 4.0, 5.7, and 8.6 on their best, average, and worst days, respectively.

Bone fractures in patients using tapentadol or oxycodone: an exploratory US claims database study.

Aim: To explore fracture outcomes with tapentadol or oxycodone, two opioids with differing mechanisms of action. Materials & methods: Retrospective cohort pilot study, using MarketScan® Commercial and Medicare Supplemental claims databases, on patients with postoperative pain, back pain, or osteoarthritis and ≥1 claim for tapentadol (n = 16,457), oxycodone (n = 1,356,920), or both (n = 15,893) between June 2009 and December 2015. Results: During 266,826 and 9,007,889 days of tapentadol and oxycodone treatment, patients evidenced 1080 and 72,275 fractures, respectively. Fracture rates per treatment-year were 1.512 for tapentadol and 3.013 for oxycodone. Conclusion: Examination of administrative claims has inherent limitations, but this exploratory analysis indicates a lower fracture rate with tapentadol than oxycodone in the analyzed dataset, which needs confirmation by further clinical trials.

Developing consensus on core outcome domains for assessing effectiveness in perioperative pain management: results of the PROMPT/IMI-PainCare Delphi Meeting.

ABSTRACT: Postoperative pain management is still insufficient, leading to major deficits, including patient suffering, impaired surgical recovery, long-term opioid intake, and postsurgical chronic pain. Yet, identifying the best treatment options refers to a heterogeneous outcome assessment in clinical trials, not always reflecting relevant pain-related aspects after surgery and therefore hamper evidence synthesis. Establishing a core outcome set for perioperative pain management of acute pain after surgery may overcome such limitations. An international, stepwise consensus process on outcome domains ("what to measure") for pain management after surgery, eg, after total knee arthroplasty, sternotomy, breast surgery, and surgery related to endometriosis, was performed. The process, guided by a steering committee, involved 9 international stakeholder groups and patient representatives. The face-to-face meeting was prepared by systematic literature searches identifying common outcome domains for each of the 4 surgical procedures and included breakout group sessions, world-café formats, plenary panel discussions, and final voting. The panel finally suggested an overall core outcome set for perioperative pain management with 5 core outcome domains: physical function (for a condition-specific measurement), pain intensity at rest, pain intensity during activity, adverse events, and self-efficacy. Innovative aspects of this work were inclusion of the psychological domain self-efficacy, as well as the specific assessment of pain intensity during activity and physical function recommended to be assessed in a condition-specific manner. The IMI-PROMPT core outcome set seeks to improve assessing efficacy and effectiveness of perioperative pain management in any clinical and observational studies as well as in clinical practice.

Quality of life and functional outcomes with tapentadol prolonged release in chronic musculoskeletal pain: post hoc analysis.

Aims: To investigate quality of life (QOL) and functionality changes in chronic pain during tapentadol prolonged release (PR) treatment. Patients & methods: Post hoc analysis of data from three Phase III trials in patients with osteoarthritis knee pain or low back pain. QOL and functionality changes were assessed by SF-36 scores. Results: All SF-36 subdomain scores improved progressively to week 3 of tapentadol titration and were sustained during 12-week maintenance treatment. Improvements in SF-36 scores were similar between tapentadol dose groups (e.g., 200 to <300 mg vs ≥500 mg), with no greater effect from higher doses. QOL and functionality improvements were consistently greater with tapentadol PR than oxycodone controlled release. Conclusion: Tapentadol PR provides consistent, clinically relevant improvements in QOL and functionality in chronic pain.

Assessing outcome in postoperative pain trials: are we missing the point? A systematic review of pain-related outcome domains reported in studies early after total knee arthroplasty.

ABSTRACT: The management of acute postoperative pain remains suboptimal. Systematic reviews and Cochrane analysis can assist with collating evidence about treatment efficacy, but the results are limited in part by heterogeneity of endpoints in clinical trials. In addition, the chosen endpoints may not be entirely clinically relevant. To investigate the endpoints assessed in perioperative pain trials, we performed a systematic literature review on outcome domains assessing effectiveness of acute pain interventions in trials after total knee arthroplasty. We followed the Cochrane recommendations for systematic reviews, searching PubMed, Cochrane, and Embase, resulting in the screening of 1590 potentially eligible studies. After final inclusion of 295 studies, we identified 11 outcome domains and 45 subdomains/descriptors with the domain "pain"/"pain intensity" most commonly assessed (98.3%), followed by "analgesic consumption" (88.8%) and "side effects" (75.3%). By contrast, "physical function" (53.5%), "satisfaction" (28.8%), and "psychological function" (11.9%) were given much less consideration. The combinations of outcome domains were inhomogeneous throughout the studies, regardless of the type of pain management investigated. In conclusion, we found that there was high variability in outcome domains and inhomogeneous combinations, as well as inconsistent subdomain descriptions and utilization in trials comparing for effectiveness of pain interventions after total knee arthroplasty. This points towards the need for harmonizing outcome domains, eg, by consenting on a core outcome set of domains which are relevant for both stakeholders and patients. Such a core outcome set should include at least 3 domains from 3 different health core areas such as pain intensity, physical function, and one psychological domain.

Cost effectiveness of a lidocaine 5% medicated plaster compared with pregabalin for the treatment of postherpetic neuralgia in the UK: a Markov model analysis.

BACKGROUND: Published analyses have demonstrated that the lidocaine (lignocaine) plaster is a cost-effective treatment for postherpetic neuralgia (PHN) relative to gabapentin or pregabalin. However, these analyses have been based on indirect comparisons from placebo-controlled trials, and there is evidence of a discrepancy between the outcomes of direct and indirect analyses. Fortunately, recent publication of the results of a head-to-head trial comparing the lidocaine plaster and pregabalin in patients with PHN or diabetic polyneuropathy allows customization of the existing model to more accurately reflect the relative cost effectiveness of these two products. OBJECTIVE: To assess the cost-effectiveness of the lidocaine 5% medicated plaster compared with pregabalin for the treatment of PHN in the UK primary-care setting. METHODS: A Markov model has been developed to assess the costs and benefits of the lidocaine plaster and pregabalin over a 6-month time horizon for the treatment of patients with PHN who are intolerant to tricyclic antidepressants and in whom analgesics are ineffective or contraindicated. The model structure allows for differences in costs, utilities (derived from published data and from the head-to-head trial) and transition probabilities between the initial 30-day run-in period and maintenance therapy, and also takes account of add-in medication and drugs received by patients discontinuing therapy. The calculation was based on data from the recent head-to-head trial described above. Additional data sources included published literature, discussions with a Delphi panel, official price/tariff lists and national population statistics. The study was conducted from the perspective of the UK National Health Service (NHS). RESULTS: The base-case analysis (1.71 lidocaine plasters per day used in the head-to-head trial for the PHN population) indicated that the total cost of treating PHN patients for 6 months with the lidocaine plaster was pound 980 per patient treated, compared with pound 784 for pregabalin (year of costing 2009). Costs for 1 month without pain and intolerable adverse events (AEs) (modified TWIST analysis) were pound 126 for the lidocaine plaster relative to pregabalin. The average patient treated with the lidocaine plaster experienced 0.321 quality-adjusted life-years (QALYs) over the 6-month period modelled compared with 0.254 QALYs for pregabalin. Quality-of-life benefits were attributed to the favourable AE profile of the lidocaine plaster. Subsequently, the lidocaine plaster cost pound 2925 per QALY gained relative to pregabalin. However, patient level longitudinal data have shown that the actual clinical usage of the lidocaine plaster is 1.1 plasters per day. If this more realistic assumption is used in the model, the total cost for a 6-month treatment period was pound 756 for the lidocaine plaster, which dominated treatment with pregabalin. Scenario analyses and sensitivity analyses had minimal impact on the results, confirming the robustness of the study. The incremental cost-effectiveness ratios for the lidocaine plaster remained well below pound 35,000 per QALY gained in all analyses. CONCLUSION: This analysis showed that the lidocaine 5% medicated plaster is a cost-effective method for obtaining sustained relief of localized neuropathic pain associated with PHN compared with pregabalin in a UK setting, in terms of both the cost per QALY gained and the cost per additional month without symptoms, when used for patients who do not experience sufficient pain relief from standard analgesics.

Developing consensus on core outcome domains and measurement instruments for assessing effectiveness in perioperative pain management after sternotomy, breast cancer surgery, total knee arthroplasty, and surgery related to endometriosis : The IMI-PainCare PROMPT protocol for achieving a consensus on core outcome domains.

INTRODUCTION: Evidence synthesis of clinical trials requires consistent outcome assessment. For pain management after surgery, inconsistency of effectiveness assessment is still observed. A subproject of IMI-PainCare (Innovative Medicine Initiatives, www.imi-paincare.eu ) aims for identifying core outcome domains and measurement instruments for postoperative pain in four surgical fields (sternotomy, breast cancer surgery, total knee arthroplasty, and surgery related to endometriosis) in order to harmonize outcome assessment for perioperative pain management. METHODS: A multifaceted process will be performed according to existing guidelines (Core Outcome Measures in Effectiveness Trials (COMET), COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN)). In a first step, outcome domains will be identified via systematic literature review and consented on during a 1-day consensus meeting by 10 stakeholder groups, including patient representatives, forming an IMI PROMPT consensus panel. In a second step, outcome measurement instruments regarding the beforehand consented core outcome domains and their psychometric properties will be searched for via systematic literature review and approved by COSMIN checklist for study quality and scale quality separately. In a three-step online survey, the IMI PROMPT consensus panel will vote for most suitable measurement instruments. The process is planned to be conducted between 11/2017 (systematic literature review on common outcome domains) and 3/2022 (final voting on core outcome measurement).

Pain assessment for chronic lower back pain: performance of the PAL-S and PAL-I patient-reported measures for symptoms and impacts.

Objective: The Patient Assessment for Low Back Pain-Symptoms (PAL-S) and the Patient Assessment for Low Back Pain-Impacts (PAL-I) were developed to incorporate patient perspective of treatment benefit in chronic low back pain (cLBP) trials. This study documents psychometric measurement properties of the PAL-S and PAL-I.Methods: In this multicenter, observational study, eligible participants clinically diagnosed with cLBP provided sociodemographic information and completed PAL measures and other patient-reported outcome measures of pain and/or disability. Confirmatory factor analyses (CFA), construct validity, and reliability were assessed.Results: The 104 participants were 61% female, 89% white, and mean age of 55 years; mean cLBP duration was 11.4 (range 0-47) years. Using painDETECT scores, 36.5% reported small likelihood of neuropathic pain, 30.8% reported unclear likelihood, and 32.7% reported definite likelihood. Persistent pain with pain attacks was reported by 38.5% of participants. CFA confirmed single components with adequate fit indices. Cronbach's alpha was 0.83 (PAL-S) and 0.87 (PAL-I), indicating reliable scales. Intraclass correlation coefficients (test-retest reproducibility, n = 44) were 0.81 (PAL-S) and 0.85 (PAL-I). PAL-S score correlation was 0.49 with Roland-Morris Disability Questionnaire (RMDQ) and 0.77 with Neuropathic Pain Symptom Inventory (NPSI). PAL-I correlated at 0.73 with RMDQ and -0.60 with Medical Outcomes Study (MOS)-36 Bodily Pain. Both measures significantly differentiated between pain intensity levels (based on numeric response scale) and painDETECT groups.Conclusion: The PAL-S and PAL-I generated highly reliable scores with substantial evidence of construct validity. Routine use of these measures in treatment trials will enhance comparability of LBP-related symptom and impact results, including patient perspective of treatment benefit.

Systematic review and network meta-analysis of the efficacy and safety of lidocaine 700 mg medicated plaster vs. pregabalin.

Objective: Neuropathic pain prevalence is estimated between 7% and 10% of the population. International guidelines recommend a variety of drugs at different therapy lines for pain relief. However, side effect profiles, for example, prompted the UK government recently to classify pregabalin and gabapentin as class C drugs. Lidocaine 700 mg medicated plaster (LMP) might be a safer alternative. A systematic review assessed how LMP and pregabalin compared in terms of efficacy and safety. The review focused on pain reduction, quality of life and adverse events in peripheral neuropathic pain (PNP) i.e. post-herpetic neuralgia, diabetic peripheral neuropathy, post-surgical/trauma, or other PNP conditions.Methods: Electronic databases were searched as well as a number of other sources up to November 2018. Sensitive strategies were used, with no restriction by language or publication status. Two independent reviewers screened records and extracted data with consensus determining final decisions. Risk of bias was assessed using the Cochrane Collaboration 2011 checklist for RCTs. Full network meta-analysis was conducted to compare LMP to pregabalin 300/600 mg in terms of pain reduction, quality of life, as well as serious adverse events and selected adverse events. Trials with enriched enrolment design were excluded.Results: Searches retrieved 7,104 records. In total 111 references pertaining to 43 RCTs were included for data extraction. Bayesian network meta-analysis of several pain outcomes showed no clear difference in efficacy between treatments However, LMP was clearly advantageous in terms of dizziness and any adverse event vs. pregabalin 600 mg/day and discontinuations vs. pregabalin 300 mg/day or 600 mg/day, as well as being associated with improved quality of life (albeit in this case based on weak evidence).Conclusions: LMP was found to be similar to pregabalin in reducing pain in all populations but had a better adverse events profile.

Cost-effectiveness of strong opioids focussing on the long-term effects of opioid-related fractures: a model approach.

Opioid analgesics are known to impact on the central nervous system (CNS). These CNS side effects, such as dizziness and confusion, have been shown to lead to an increased risk of falling with subsequent fractures in elderly patients being treated with opioids. The risk of experiencing fractures has been shown to be dependent on the substance administered. Therefore, a health economic model was developed to investigate the cost-effectiveness of the most commonly used strong opioids in Germany, focussing on opioid-related fractures. By means of a Markov model, the consequences of hip, spine and forearm fractures due to the prior administration of transdermal (TD) buprenorphine, TD fentanyl, oral oxycodone as well as oral morphine were assessed from the perspectives of the German statutory health insurance (SHI) and the German social security (GSS) system over a time horizon of 6 years. The most frequently prescribed strength/package-size combinations of these opioids were taken into consideration, including generics where available. The results of the present analysis predict that TD buprenorphine is dominant compared to TD fentanyl and oxycodone by showing better effects [life years gained/quality adjusted life years (QALY) gained] at lower cost. From the SHI perspective, the incremental cost-effectiveness ratio (ICER) compared to morphine is 6,801.61 per life year gained, and 7,766.11 per QALY gained. From the GSS perspective, the ICER is 2,496.77 per life year gained and 2,850.83 per QALY gained. The model is robust regarding probabilistic variations of all parameters in the sensitivity analyses. Focussing on fractures due to the prior administration of strong opioids, TD buprenorphine is less costly and more effective than TD fentanyl and oxycodone and represents a cost-effective treatment option versus morphine in patients with chronic pain from both the SHI and GSS perspective in Germany.

Cost-effectiveness analysis of a lidocaine 5% medicated plaster compared with gabapentin and pregabalin for treating postherpetic neuralgia: a german perspective.

OBJECTIVE: This study set out to assess the cost effectiveness of using a 5% lidocaine (lignocaine) medicated plaster for the treatment of postherpetic neuralgia (PHN) compared with gabapentin, pregabalin 300 mg/day or 600 mg/day in German primary care. The analysis took the perspective of the Statutory Health Insurance scheme (GKV). METHODS: A Markov model was used to calculate the costs (2007) and benefits of the lidocaine plaster, gabapentin 1800 mg/day and pregabalin 300 or 600 mg/day over a 6-month time horizon in elderly patients with PHN who experienced insufficient pain relief with standard analgesics and could not tolerate or had contraindications to tricyclic antidepressants. The model calculated the cost per quality-adjusted life-year (QALY) gained and the cost per additional month without symptoms or intolerable adverse effects. The majority of transition probabilities were obtained from randomized controlled trials identified from a systematic literature review. Further model inputs, including resource use, concomitant medication and long-term efficacy/adherence data, were obtained from a Delphi panel. Utility values were taken from a previous study and age adjusted. Cost data were obtained from official price tariffs. Mortality, indirect costs and costs associated with inpatient treatment were not considered in the present analysis due to the perspective and time horizon employed. RESULTS: Over the 6-month period modelled, the mean total therapy cost per patient treated with the lidocaine plaster was euro911, compared with euro728 for gabapentin, euro875 for pregabalin 300 mg/day and euro977 for pregabalin 600 mg/day. Treatment with the lidocaine plaster was related to greater numbers of QALYs and more months without symptoms or intolerable adverse effects (mean 0.300 QALYs and 4.06 months per patient) than with gabapentin (mean 0.247 QALYs and 2.72 months), pregabalin 300 mg/day (mean 0.253 QALYs and 3.02 months) or pregabalin 600 mg/day (mean 0.256 QALYs and 3.22 months). The lidocaine plaster cost euro3453/QALY gained and euro137 per additional month without adverse effects or symptoms relative to gabapentin and euro766/QALY and euro35 per month without adverse effects or symptoms relative to pregabalin 300 mg/day. The lidocaine plaster dominated pregabalin 600 mg/day, being less costly and more effective. Probabilistic sensitivity analysis indicated that there is a 99.36% chance that the lidocaine plaster is the most clinically effective treatment considered in the analysis and a 99.09% chance that the lidocaine plaster is the most cost-effective treatment of the four therapies considered in the analysis if the GKV is willing to pay at least euro20 000/QALY gained. Extensive deterministic sensitivity analyses demonstrated that the findings are robust. CONCLUSIONS: The 5% lidocaine-medicated plaster is a cost-effective treatment option for the management of PHN in Germany compared with gabapentin and both 300 and 600 mg/day of pregabalin.

Mixed-methods development of a new patient-reported outcome instrument for chronic low back pain: part 2-The Patient Assessment for Low Back Pain-Impacts (PAL-I).

We describe qualitative and quantitative development and preliminary validation of the Patient Assessment for Low Back Pain-Impacts (PAL-I), a patient-reported outcome measure for use in chronic low back pain (cLBP) clinical trials. Concept elicitation and cognitive interviews (qualitative methods) were used to identify and refine symptom concepts. Classical test theory and Rasch measurement theory (quantitative methods) were used to evaluate item-level and scale-level performance of the PAL-I using an iterative approach between qualitative and quantitative methods. Patients with cLBP participated in concept elicitation interviews (N = 43), cognitive interviews (N = 38), and assessment of paper-to-electronic format equivalence (N = 8). A web-based sample of self-reported patients with cLBP participated in quantitative studies to evaluate preliminary (N = 598) and revised (n = 401) drafts and patients with physician-diagnosed cLBP (N = 45) participated in preliminary validation of the PAL-I. The instrument contained 9 items describing cLBP impacts (walking, sitting, standing, lifting, sleep, social activities, travelling, climbing, and body movements). Item-level performance, scale structure, and scoring seemed to be appropriate. One-week test-retest reproducibility was acceptable (intraclass correlation coefficient 0.88 [95% confidence interval, 0.78-0.94]). Convergent validity was demonstrated with PAL-I total score and Roland-Morris Disability Questionnaire (Pearson correlation 0.82), MOS-36 Physical Functioning (-0.71), and MOS-36 Bodily Pain (-0.71). Individual item scores and total score discriminated between numeric rating scale tertile groups and painDETECT categories. Interpretation of paper and electronic administration modes was equivalent. The PAL-I demonstrated content validity and is potentially useful to assess treatment benefit in clinical trials of cLBP therapies.