Hiltrud Liedgens

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

BackgroundAssessments 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.MethodsPooled 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.ResultsThe 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.ConclusionsThis 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.

The impact of pain on labor force participation, absenteeism and presenteeism in the European Union

Abstract Objectives: The aims of this paper are to generate estimates of the association between the experience and burden of pain, by severity and frequency, with (1) labor force participation and workforce status in five EU countries (the UK, France, Spain, Germany and Italy) and (2) patterns of absenteeism and presenteeism for the employed workforce. Methods: Data are from the internet-based 2008 National Health and Wellness Survey (NHWS). This survey covers both those who report experiencing pain in the last month as well as the no pain population. A series of regression models are developed with the no pain group as the reference category. The impact of pain, categorized by severity and frequency reported, is assessed within a labor supply framework for (1) labor force participation and (2) absenteeism and presenteeism. In the former case both binomial and multinomial logistic models are estimated; in the latter case ordered logit models are estimated. Results: The results demonstrate that, in the context of health status, the experience of frequent severe and moderate pain has a dominant, independent and negative association with labor force participation and employment status as well as absenteeism and presenteeism. The presence of severe daily pain is associated with a 20-point reduction in the probability of being employed full-time; with moderate daily pain associated with a 10-point reduction. The impact of pain is far greater than the potential impact of other health status measures (e.g., chronic comorbidities and BMI). The experience of pain, notably severe and frequent pain, also outstrips the impact of other health status factors in absenteeism and presenteeism. Conclusions: The experience of pain, in particular severe daily pain, has a substantial negative association with labor force participation in these five European countries as well as reported absenteeism and presenteeism. As a measure of health status, it clearly outweighs other health status measures. Whether or not pain is considered as a disease in its own right, the experience of chronic pain, as defined here, presents policy makers with a major challenge. Programs to relieve the burden of pain in the community clearly have the potential for substantial benefits from societal, individual and employer perspectives.

The societal impact of pain in the European Union: health-related quality of life and healthcare resource utilization

Abstract Objectives: This paper reports on the results of a series of quantitative assessments of the association of severe and frequent pain with health-related quality of life and healthcare resource utilization in five European countries. Methods: The analysis contrasts the contribution of the increasing severity and frequency of pain reported against respondents reporting no pain in the previous month. The data are taken from the 2008 National Health and Wellness Survey. Single-equation generalized linear regression models are used to evaluate the association of pain with the physical and mental component scores of the SF-12 questionnaire as well as health utilities generated from the SF-6D. In addition, the role of pain is assessed in its association with healthcare provider visits, emergency room visits and hospitalizations. Results: The results indicate that the experience of pain, notably severe and frequent pain, is substantial and is significantly associated with the SF-12 physical component scores, health utilities and all aspects of healthcare resource utilization, which far outweighs the role of demographic and socioeconomic variables, health risk factors (in particular body mass index) and the presence of comorbidities. In the case of severe daily pain, the marginal contribution of the SF-12 physical component score is a deficit of −17.86 compared to those reporting no pain (population average score 46.49), while persons who are morbidly obese report a deficit of only −6.63 compared to those who are normal weight. The corresponding association with health utilities is equally dramatic with a severe daily pain deficit of −0.19 compared to those reporting no pain (average population utility 0.71). Conclusions: For the five largest EU countries, the societal burden of pain is considerable. The experience of pain far outweighs the contribution of more traditional explanations of HRQoL deficits as well as being the primary factor associated with increased provider visits, emergency room visits and hospitalizations.

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

AbstractObjective: 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 €911, compared with €728 for gabapentin, €875 for pregabalin 300 mg/day and €977 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 €3453/QALY gained and €137 per additional month without adverse effects or symptoms relative to gabapentin and €766/QALY and €35 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 €20 000/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.

Cost-effectiveness of tapentadol prolonged release compared with oxycodone controlled release in the UK in patients with severe non-malignant chronic pain who failed 1st line treatment with morphine

Abstract Objectives: The aim of this analysis was to assess the cost-effectiveness of tapentadol PR (prolonged release) compared with oxycodone CR (controlled release) in severe non-malignant chronic pain patients in whom controlled release morphine was ineffective or not tolerated. Methods: A Markov model was developed to assess costs and benefits over a 1-year time horizon from the National Health Service perspective in the UK. Patients could either continue on 2nd line therapy or switch to 3rd line opioid due to lack of efficacy or poor tolerability. Patients failing also 3rd line therapy entered the final absorbing health state (4th line). Data on tolerability, efficacy, and utilities for tapentadol and oxycodone were obtained from the three comparative phase III clinical trials. Costs of resource consumption associated with opioid treatment were derived from a retrospective database analysis of anonymized patient records. Results: The model results predicted that initiating 2nd line therapy with tapentadol leads to higher effectiveness and lower costs vs oxycodone. For the overall population included in the clinical trials, mean annual costs per patient when treated with tapentadol and oxycodone were £3543 and £3656, respectively. Treatment with tapentadol, while cheaper than oxycodone, was more effective (0.6371 vs 0.6237 quality-adjusted life years (QALYs) for tapentadol and oxycodone, respectively), meaning that tapentadol dominated oxycodone. For the sub-group of opioid-experienced patients with severe pain at baseline the ranking in terms of costs and QALYs remained unchanged. Extensive sensitivity analyses showed that conclusions about the cost-effectiveness are consistent. Conclusions: The cost-effectiveness study suggested that initiating 2nd line treatment in patients with severe non-malignant chronic pain in the UK with tapentadol instead of oxycodone improves patients’ quality-of-life and is less costly. Key limitations when interpreting the results are the use of different sources to populate the model and restricted generalizability due to data extrapolation.

Cost-Effectiveness of Tapentadol in Severe Chronic Pain in Spain: A Cost Analysis of Data From RCTs

BACKGROUND Chronic pain is known to be a significant and common health problem. Tapentadol, a recently developed centrally active, oral analgesic agent is used to treat adults with severe chronic pain that can be adequately managed only with opioid analgesics. Tapentadol has been reported to provide an improved adverse-events (AE) profile compared with other potent opioid analgesics at similar levels of analgesia. OBJECTIVES The aim of this study was to compare the cost-effectiveness of tapentadol to that of opioids commonly used as first-line treatment of severe, chronic, nonmalignant pain from the perspective of the health care payer in Spain. METHODS A Markov state-transition model was developed to compare the cost-effectiveness of first-line treatment with tapentadol to that of oxycodone, morphine, and transdermal fentanyl (TDF) over a 1-year time horizon. Four health states were defined: (1) treatment discontinuation due to a severe AE; (2) treatment discontinuation due to a lack of efficacy; (3) occurrence of an AE that required medical treatment; and (4) no discontinuation and no AE. If a patient discontinued a treatment, he or she was switched to an alternative, second-line opioid. Data regarding efficacy, tolerability, and utility values (EQ-5D) were derived from randomized clinical trials. Clinical experts estimated the rates of switching to other opioids and the health care resource utilization associated with the treatment of severe chronic pain. Unit costs were derived from public price lists/tariff works and were calculated from the perspective of the National Spanish Health System. The robustness of the model results was tested in extensive sensitivity analyses in which event probabilities, costs, utilities, and treatment-switching rates were altered. RESULTS Data from 3 studies (1981 patients) were included in the model. Overall, the model predicted that initiating first-line treatment with tapentadol in patients with severe, chronic, nonmalignant pain was associated with lower costs and greater efficacy versus first-line treatment with oxycodone. Compared with morphine and TDF, tapentadol yielded incremental cost-effectiveness ratios of €2656 and €2069 per quality-adjusted life-year gained, respectively. On extensive 1-way and scenario analyses, findings on the cost-effectiveness of tapentadol were consistent. The probability that tapentadol would be cost-effective compared with each comparator at the willingness-to-pay threshold of €20,000 to €30,000/QALY gained exceeded 90%. CONCLUSIONS Based on the findings from the present model, tapentadol is likely to be a cost-effective first-line treatment in patients with severe, chronic, nonmalignant pain in Spain according to the commonly accepted willingness-to-pay thresholds. Compared with morphine and TDF, the incremental cost-effectiveness ratios were low; compared with oxycodone, tapentadol dominated, showing better quality-of-life outcomes at lower costs.

Cost Effectiveness of a Lidocaine 5% Medicated Plaster Compared with Pregabalin for the Treatment of Postherpetic Neuralgia in the UK: A Markov Model Analysis

AbstractBackground: 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 £980 per patient treated, compared with £784 for pregabalin (year of costing 2009). Costs for 1 month without pain and intolerable adverse events (AEs) (modified TWIST analysis) were £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 £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 £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 £35000 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.

A burden of illness study for neuropathic pain in Europe

Purpose Neuropathic pain (NP) is often severe and represents a major humanistic and economic burden. This study aimed at providing insight on this burden across France, Germany, Italy, Spain, and the UK, considering direct and indirect costs, productivity loss, and humanistic impact on patients and their families. Methods Physician questionnaires provided data on patients presenting with NP covering demographics, sick leave and retirement, number of consultations, drug treatments, and surgical procedures. Patients provided further demographic and disease-related data and completed the Work Productivity and Activity Impairment (WPAI), the EuroQol 5-Dimension (EQ-5D), and the Brief Pain Inventory (BPI) questionnaires. All health-related direct unitary costs were collected from relevant country-specific sources and adjusted to 2012 prices (€) where necessary. A subgroup analysis of costs based on diabetic peripheral neuropathy (n=894), fibromyalgia (n=300), and low back pain (n=963) was performed. Findings About 413 physicians completed a total of 3,956 patient records forms. Total annual direct health-care costs per patient ranged from €1,939 (Italy) to €3,131 (Spain). Annual professional caregiver costs ranged from €393 (France) to €1,242 (UK), but this only represented a small proportion of total care because much care is provided by family or friends. Sick leave costs ranged from €5,492 (UK) to €7,098 (France), with 10%–32% patients prevented from working at some point by NP. Total cost (including direct and indirect costs) of NP per patient was €10,313 in France (69% of the total cost), €14,446 in Germany (78%), €9,305 in Italy (69%), €10,597 in Spain (67%), and €9,685 in the UK (57%). Indirect costs (ie, sick leave) constituted the majority of costs in all five countries: €7,098 in France, €11,232 in Germany, €6,382 in Italy, €7,066 in Spain, and €5,492 in the UK. In the subgroup analysis, total annual direct costs per patient were highest for neuropathic back pain and radiculopathy, and lowest for fibromyalgia. Mean WPAI score range was 34.4–56.1; BPI interference was 4.1–4.8; and EQ-5D was 0.57–0.74. The results suggest that a significant proportion of the patient’s work time in the previous week was affected by NP, and these are relatively high compared with other diseases such as diabetes, respiratory conditions, and arthritis. Implications Despite differences in practice between countries, these findings suggest a high opportunity cost for society in terms of lost work and productivity due to NP. The wider costs appear significantly higher to patients, carers/families, and society as a whole than to the health system alone.

Time since diagnosis, treatment pathways and current pain status: a retrospective assessment in a back pain population

Abstract Objectives: The purpose of this study is to report on long-term treatment patterns in a back pain population and to consider whether these may be considered as reflective of under-treatment of pain or poor pain control. Methods: Data are from a commissioned recontact SELECT survey of persons who had previously reported experiencing pain in the 2010 National Health and Wellness Survey. The analysis covers five countries: the UK, France, Spain, Germany and Italy. It is restricted to patients who reported moderate or severe pain in the last 3 months and who were judged to be experiencing back pain from the pain conditions reported. A total of 1018 subjects met the back pain criteria. Of these, 738 had their back pain initially diagnosed by a physician. It is this latter group that is the focus for the analysis. Subjects were further allocated to categories to assess potential pain chronicity and the intensity and self-limiting aspects of pain experience. Results: Irrespective of the pain classification used, 56.10% of subjects in this back pain population report their first physician diagnosis of pain as occurring at least 6 years ago. At the same time 36.81% report experiencing severe pain in the last 3 months and 63.69% moderate pain. Overall, 53.11% of respondents are assessed as experiencing probable chronic pain and 24.12% as possible chronic pain. Among those experiencing probable chronic pain, 61.48% were diagnosed with back pain more than 6 years ago. In addition, 43.22% of respondents found the impact of pain on daily activities to be severely limiting and 22.63% found it to be moderately limiting. The majority of subjects, whether they were diagnosed and treated initially by primary care or another physician specialty, apparently experience no change in their treatment regimen. The absence of treatment change is 69.03% in the case of those experiencing severe pain and 84.89% in the case of those with moderate pain (p < 0.05). Limitations: The NHWS is an internet survey, as a self-report there is no separate validation of pain experience reported; as subjects are asked to recall pain and treatment experience there is the possibility of recall error and bias. Conclusions: Two features of this analysis stand out: (i) time since first diagnosis of pain for those currently experiencing severe or moderate back pain and (ii) the ‘inertia’ that appears to characterize long-term treatment decisions. Irrespective of current pain status, 70% or more of those experiencing current severe or moderate pain report no change from their initial treating physician or no change in prescription once referred to a pain specialist. This occurs over an extended time frame. Whether this should be interpreted as a failure in pain management is a moot point. The fact remains, however, that despite time since first diagnosis subjects not only currently experience severe or moderate pain but a substantial proportion may be expected to continue.

Health economic evidence of 5% lidocaine medicated plaster in post-herpetic neuralgia

Background Post-herpetic neuralgia (PHN) is the most common and most debilitating complication of herpes zoster, and involves considerable associated costs. Objective This paper presents results from nine health economic studies undertaken in eight European countries that compared lidocaine medicated plaster with gabapentin and/or pregabalin in PHN. It aims to support the increasing need for published cost-effectiveness data for health care decision-making processes in Europe. Methods All studies were based on a similar core Markov model with data derived from clinical trials, local Delphi panels, and official national price and tariff lists. The main outcome measure was cost per quality-adjusted life year gained; time without pain or intolerable adverse events was also included as a secondary outcome measure. All studies focused on an elderly population of patients with PHN who had insufficient pain relief with standard analgesics and could not tolerate or had contraindications to tricyclic antidepressants. Results Despite considerable differences in many of the variables used, the results showed remarkable similarity and suggested that use of lidocaine medicated plaster offered cost-savings in many of the countries studied, where it proved a highly cost-effective alternative to both gabapentin and pregabalin. Conclusion Lidocaine medicated plaster is a cost-effective alternative to gabapentin and pregabalin in the treatment of PHN. These savings are largely the result of the superior safety profile of the lidocaine medicated plaster.