Original Title: Efectividad, seguridad y coste-efectividad de la adhesiolisis epidural para el tratamiento del síndrome de cirugía fallida de espalda

Authors' objectives: • To systematically review the available scientific literature on the efficacy, effectiveness, safety and efficiency of epidural adhesiolysis in patients with chronic pain refractory to pharmacologic treatment due to FBSS. • To estimate the cost-effectiveness of the epidural adhesiolysis for the treatment of FBSS from the perspective of the Spanish Health National Service.

Authors' results and conclusions: RESULTS: SYSTEMATIC REVIEW: A total number of 31 articles was included in this review: 14 secondary studies and 17 articles related to primary studies which included 4 randomized controlled trials (reported in 6 articles), a retrospective comparative study, and 10 other observational studies informing on safety issues. We did not identify any full economic evaluation. Main results are the following: Methodological quality of the clinical trials was acceptable if we take into account that the treatments compared are all interventional, and therefore some biases are just impossible to control. However, most studies present an important number of dropouts, especially in the control group and in the medium term. Three out of four trials included were carried out by the same research group from the USA, led by Dr. Manchikanti in a private practice, with no external funding. The remaining trial was conducted in China. All trials compared epidural adhesiolysis with epidural steroid injections. The interventions differed among studies regarding the number of procedures, route of approach, or the concentration of the saline solution. Also, the type of patients differed from one study to the other. Two studies included a mix of patients with chronic pain due to FBSS or other causes, while the other two studies included 100% FBSS patients. The studies conducted by Manchikanti et al. found significant differences between the intervention and the control group at 3 and 6 months for the two primary outcome measures, pain and functional status. The Chinese study and the retrospective comparative study included in the review found similar results consistent with those from Manchikanti et al. We observed a significant improvement in pain and functional status at 3 months in three trials comparing percutaneous adhesiolysis, including steroids and normal or hypertonic saline, with steroid injections in a sample of mainly FBSS patients. Another trial also found differences favorable to percutaneous adhesiolysis with hypertonic saline versus steroid injections at 6 months in FBSS patients. Only one study assessed endoscopic adhesiolysis with favorable results at 3 months. Meta-analysis results are favorable to adhesiolysis for pain and functional status when compared to the control group at 3 and 6 months. Nevertheless, the indirectness of evidence and the risk of serious or very serious bias make the quality of evidence for adhesiolysis effectiveness as low or very low at 6 and 12 months for pain and functional status. The existence of risk of bias comes from the high rate of dropouts in the control group during the follow-up period. The risk of bias regarding the measure of opioid intake is very serious, mainly because in one of the studies the groups are very different at baseline regarding this variable. Moreover, none of the studies assessed the health-related quality of life. For the review on treatment safety, we included 4 trials and 10 observational studies. The methodological quality of the latter studies is low. All studies define the assessment of safety and adverse effects as one of their research goals. A trial with 120 participants (60 in each arm) reported 7 adverse events in the adhesiolysis group, while two other trials reported only one event in each interventional group. In the observational studies, a study specifically designed for research on the complications associated with the procedure stands out. Complications were generally infrequent but some could be serious. Besides, the endoscopic version of the technique seems to have more adverse events than the percutaneous one. ECONOMIC EVALUATION: According to the base case, the most effective and costly strategy is epidural adhesiolysis. The ICER is 11,024 €/QALY. For a cost-effectiveness threshold of 30,000 €/QALY, adhesiolysis is a cost-effective alternative. According to the deterministic sensitivity analysis, the parameters with higher impact on the ICER are the probabilities of pain relief after adhesiolysis, the number of adhesiolysis procedures in one year and its cost, and utilities for both considered states. However, the ICER values never exceed the 30,000 €/QALY threshold. Scenario analysis shows that even in the most favorable scenario for epidural adhesiolysis, it never saves resources although the ICER value is very low. For the scenario that represents clinical practice in Spain, the ICER is 15,003 €/QALY, again below the 30,000 €/QALY threshold. The probabilistic sensitivity analysis shows that for some simulations, adhesiolysis could be more costly and also less effective. 80% of simulations are below the 30,000 €/QALY threshold. In the case of much higher thresholds (even as high as 100,000 €/QALY), the probability of adhesiolysis being cost-effective is not able to reach a 90% level. CONCLUSIONS: • Percutaneous epidural adhesiolysis is more effective than epidural injections of steroids for the reduction of pain and functional disability at 3 months in patients with FBSS. • Percutaneous epidural adhesiolysis could be more effective than epidural injections of steroids for the reduction of pain and functional disability at 6 months in patients with FBSS. • The low quality of the available evidence does not allow for conclusive statements about the effectiveness of percutaneous epidural adhesiolysis at 6 and 12 months. • Only one study assessed the effectiveness of endoscopic adhesiolysis. According to this study the endoscopic adhesiolysis is more effective than epidural injections of steroids for the reduction of pain and functional disability at 3 months in patients with FBSS. • High methodological quality studies are needed in which pain, functional status and other outcomes like those related to health related quality of life are measured in the long term. It is especially necessary the evaluation of endoscopic adhesiolysis and the comparison with the percutaneous technic. • Epidural adhesiolysis may involve complications, some of them quite serious (sensory deficits, organic dysfunctions, infections related to the procedure). An appropriate way to tackle the chances of complications could be to establish detailed guidelines in order to diminish variabilities and to assure that practitioners are well trained and experienced. • From the perspective of the Spanish National Health Service and for a cost-effectiveness threshold of 30000 €/QALY, the probability of percutaneous epidural adhesiolysis to be a cost-effective alternative when compared to epidural steroids injections for the treatment of FBSS is 80%.

Authors' recommendations: We suggest including the epidural adhesiolysis in National Health Service for the treatment of chronic low back pain secondary to failed back surgery syndrome (strength of recommendation: weak). Other recommendations: The implementation of epidural adhesiolysis in the National Health Service should follow guidelines developed with scientific rigour and agreed by experts. These protocols should involve the collection of use of resources and health outcomes data in order to allow the assessment of the technic. Patients should be informed of epidural adhesiolysis risks and benefits, enabling a proper shared and informed decision making.

Authors' methods: SYSTEMATIC REVIEW: We conducted a systematic search for articles in the electronic databases The Cochrane Library Plus (CENTRAL, Cochrane Systematic Reviews Database), MEDLINE, PREMEDLINE, NHS CRD (DARE, HTA, NHS-EED), SCOPUS, Science Citation Index, EMBASE, and PEDRO, up to March 2015. We also hand-searched the references of the included articles and identified systematic reviews. We searched clinicaltrials.gov and contacted the authors of the studies when needed. Studies were eligible for inclusion if they met these criteria: a) Participants: adults of any gender and ethnic origin suffering from low back chronic pain secondary to FBSS and refractory to other treatment alternatives, and eligible for adhesiolysis; b) Interventions: percutaneous or endoscopic adhesiolysis including a wide range of possible comparators; c) Design and outcomes: comparative studies assessing, at least, pain or functional status (review on adhesiolysis effectiveness), including also observational studies for the review on safety, and full economic evaluations for the review on cost-effectiveness. Two independent reviewers selected the studies. Data extraction of the included studies was carried out by one reviewer and verified by a second one. Both reviewers discussed their decisions and in the event of any differences, they were resolved through discussion with a third member of the team until consensus was reached. We collected the data in electronic forms designed ad hoc. Methodological quality of the studies was assessed using different tools depending on the design. Quality of the evidence and strength of recommendations was assessed using the GRADE approach. The information gathered was summarized through a narrative synthesis and the results were shown in tables. We conducted a meta-analysis of studies for the two primary outcomes. ECONOMIC EVALUATION: We performed a cost-effectiveness analysis comparing costs and quality-adjusted life years (QALY) of two therapeutic procedures for chronic back pain treatment secondary to FBSS: percutaneous epidural adhesiolysis and injections of epidural steroids. A decision tree was depicted to represent the therapeutic process for one year. For the analysis, we used the perspective of the National Health Service, therefore we only included direct medical costs related to the compared procedures, that is, cost of interventions, costs of severe complications, and cost of analgesics. Unit costs are taken from different sources and were expressed in EUROS 2015. The values for probabilities used in the base case were estimated from both the figures of one randomized clinical trial and some assumptions based on the available literature. The interventions can result in significant pain relief, that is, 50% or more reduction on a scale such as the visual analogue scale. In the case of utilities related to the two possible health states, with or without pain relief higher than 50%, values from previous economic evaluations were used. Estimated results of the therapeutic options' costs and effectiveness were combined by means of the incremental cost-effectiveness ratio (ICER). We conducted deterministic sensitivity analyses on the parameters carrying some uncertainty and also probabilistic sensitivity analysis including the acceptability curve.

Project Status: Completed

Year Published: 2015

URL for published report: https://sescs.es/efectividad-de-la-adhesiolisis-epidural-para-el-tratamiento-del-sindrome-de-cirugia-fallida-de-espalda/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Canary Health Service

Contact Address: Dirección del Servicio. Servicio Canario de la Salud, Camino Candelaria 44, 1ª planta, 38109 El Rosario, Santa Cruz de Tenerife

Contact Name: sescs@sescs.es

Contact Email: sescs@sescs.es