Translating Evidence into Practice The case of Neuroreflexotherapy in the

1. Translating Evidence into Practice The case of Neuroreflexotherapy in the Spanish National Health Service Francisco Kovacs, MD, PhD Spanish Back Pain Research Network kovacs@kovacs.org

2. Neuroreflexotherapy Intervention (NRT) • Implantation of surgical material into the skin, to deactivate the neurons involved in Pain, Muscle Contracture and Neurogenic Inflammation • Without anesthesia, on an outpatient basis • Surgical single use, sterile material: • Dermic burins, fall out alone ≈ 10 days • Surgical staples, extracted at 90 days

3. The Process: Implementing a Health Technology … in an “ideal world” scenario RCT(s) vs. Placebo / “Sham”: Efficacy + Safety From Evidence RCT(s) vs. Existing Treatments: Effectiveness + Efficiency + Safety Review of Evidence Planning: Application Conditions + Surveillance Mechanisms To Practice Pilot: Feasibility + Safety Generalization + Surveillance: Results + Optimization + Safety

4. The Implementation Process which NRT followed • MedClin (Barc) 1993; 101: 570-5, Spine1997;22:786-97 RCT(s) vs. Placebo / “Sham”: Efficacy + Safety • Spine 2002;27: 1149-1159 RCT(s) vs. Existing Treatments: Effectiveness + Efficiency + Safety • Cochrane Database of Systematic Reviews 2004;2:CD003009, • Spine 2005;30:E148–53, • Agencies for HTA: ISCIII; AATRM, Avalia-t 1996-2002 • Scientific societies 1996-2002 Review of Evidence Planning: Application Conditions + Surveillance Mechanisms • INSALUD 2002 • Ib-Salut 2004, SESPA 2005, SMS 2007 • SERMAS 2008 CatSalut 2006-2010 Pilot: Feasibility + Safety • Gaceta Sanitaria 2004;18:275–86 • HealthPolicy 2006; 79:345-357 (Feasiblity + Results + Safety + Satisfaction) • Spine 2007;32:1621-1628 • (prognosticfactors for refinment of indicationcriteria) Generalization + Surveillance: Results + Optimization + Safety

5. RCTs and Review of Evidence The Cochrane Systematic Review:

6. RCTs and Review of Evidence The Cochrane Systematic Review: • “The main finding of this review is that NRT appears to be a safe and effective intervention for the short-term treatment of chronic nonspecific LBP” • Cochrane Database of Systematic Reviews 2004;2:CD003009

7. Planning Application conditions in the Spanish NHS • Application conditions consistent with those used in the RCTs: • Indication criteria = neck or back pain: • ≥ 3 VAS points • ≥ 14 days • Not caused by fracture, systemic diseases or neurogenic claudication due to lumbar spinal stenosis • Interventions performed: • By certified physicians • In Certified Units which incorporate: • Mechanisms for quality control (% of missing data, time spent with patients, anonimous patients’ satisfaction survey, etc.) • Standardized mechanisms for post-implementation surveillance • Standardized referral protocol from primary care

8. Pilot Study & Post-Implementation Surveillance The process • Application conditions, consistent with those in RCTs • All methods, previously validated and pilot tested Independent analysis Referral Intervention Discharge • Gac Sanitaria 2004;18:275–86 Health Policy 2006; 79:345-357 Spine 2007;32:1621-1628

9. Pilot Study & Post-Implementation Surveillance The process • Application conditions, consistent with those in RCTs • All methods, previously validated and pilot tested Independent analysis Referral Intervention Discharge • Age, gender • Duration of the episode and time elapsed since first diagnosis • Previous diagnostic tests and findings • Previous treatments • Pain (VAS) • Referred pain (VAS) • Disability (RMQ, NDI) • Results of physical examination • Appropriate-ness of referral • Waiting time • Technical characteristics of NRT intervention • Skin sensitivity tests • Immediate adverse events • Tolerance to pain from implantation of the material • Diagnostic tests • Other treatments • Number of NRT interventions • Pain (VAS) • Referred pain (VAS) • Disability (RMQ, NDI) • Adverse events • Process duration • Diagnostic tests • Physical examination • Treatments • Pain (VAS) • Referred pain (EVA) • Disability (RMQ, NDI) • Patients’ satisfaction (anonymous patient satisfaction survey, 11 items) • Rates (appropriate referral, refusal, re-intervention, etc.) • Clinical evolution • Prognostic factors • Satisfaction: • Referring physicians • Patient telephone survey (random sample) • Gac Sanitaria 2004;18:275–86 Health Policy 2006; 79:345-357 Spine 2007;32:1621-1628

10. Post-implementation Surveillance Analysis conducted by Health Authorities

11. Post-implementation Surveillance Main results in the routine practice of the Spanish NHS • Results consistent with those from previous RCTs and the Pilot Study • Effectiveness: Safety: • Skinirritation / infection: 3.3% Earlyextraction: 0.2% • Contact dermatitis: 1 case out of 162.678 patients Satisfaction: would recommend NRT to a relative: • Referring physicians: 92.5% Patients: 95.8% Organizational and economic results: • Appropriate referral from primary care: 95.5% • Significant reduction in the use of other Health Resources: Net savings • 3 € for each euro invested • 3 Million per year / 1 Million inhabitants (constant 2007 €) • Gac Sanit 2004;18:275–86 , Health Policy 2006; 79:345-357, IX Intnal Forum on LBP Research 2007, Spine 2007;32:1621-1628

12. The Evidence: • Clinical and ethical aspects: • Very few treatments have proven to be effective and safe for subacute and chronic low back pain • NRT improves effectiveness of usual treatment (by between 289% and 636%) • Economic reasons: • NRT improves cost/effectiveness (by between 1,385% and 2,180%) • NRT saves 3 € for each euro invested, every year • Estimated savings in Spain: 130 M €, every year • Feasibility: • NRT has been successfully implemented in routine practice, in the application conditions in which it was assessed • Consistent satisfactory results, across the Health Services where it has been implemented • Evidence suggests NRT should be generalized across the Spanish NHS

13. The Reality: • NRT iscurrentlyimplemented in onlythreeregionswithintheSpanishNationalHealthService • The Balearic Islands • Asturias • Catalonia

14. Key Obstacles: Review of Evidence Incongruities and double standards (1/2) • Isn’t this common to all interventional procedures? “NRT is only performed by a few highly trained practitioners in Spain” • Would it be better if performed by untrained individuals? • What is wrong with Spain? • Were these data requested for any other interventional procedures (surgery, CBT, injections, etc.)? “No data are available on the ease and timeframe needed to achieve the required level of expertise” • In fact, education and training standards set by the corresponding Society are publicly available (www.AEMEN.es) • Consistent results across: RCTs and routine clinical practice, different practitioners, Primary Care and Hospital settings, different geographical locations and Health Services “Doubts remain on reproducibility of results...” • … Is this still a “Spain issue”? “Doubts remain on reproducibility of results outside Spain” • Disability may be influenced by cultural factors, but differences in pain perception are mainly genetic. Are we suggesting that Spanish patients are genetically different from the French, Portuguese, Italians, etc.? • Were similar doubts raised when psychological treatments for disability were assessed in Northern Europe (CBT, graded activity, etc.)?

15. Key Obstacles: Review of Evidence Incongruities and double standards (2/2): • Would it have been preferable if no trained practitioner had participated in the design or conduction of the RCTs? “The principal investigator (who is also a leading NRT practitioner) was involved in all of the published RCTs (albeit with different research teams)” • All mechanisms to prevent the “principal investigator” from influencing results were put into practice: • Conduction of RCTs, monitored by independent researchers from governmental agency • Audit of tape recorded conversations with patients • He did not have access to recruitment, treatment allocation, data or statistical analysis • Consistent results across RCTs, despite different practitioners, different research teams, and different settings “Lack of clarity regarding scarring from staples” • Not requested for other procedures (e.g., surgery)

16. Key Obstacles: Review of Evidence Lets put this comment into perspective… … What do we mean by “Scarring”? NRT SURGERY

17. Key Obstacles: The Red Tape How should NRT be generalized across the Spanish NHS? • Two mechanisms are possible: • Option I.At the regional level: one region at a time • The decision is made in each region, and rolled out gradually across the 17 regions, one region at a time. • Option II. At the National level: all regions simultaneously • The decision is made in centrally, and rolled out across all 17 regions simultaneously

18. Key Obstacles: The Red Tape The process at the regional level: • Each regional government • Decides which health technologies it will cover • May (or may not) request a report from its own “Agency for Health Technology Assessment” or equivalent regional Department • If it requests a report, may (or may not) take recommendations on board • The process must be repeated 17 times

19. Key Obstacles: The Red Tape The process at the National level: • For non-pharmacological technologies (diagnostic or therapeutic), decisions on coverage must be approved by the National Health Board • National Health Board • Minister of Health • Regional Ministers of Health (17) • Senior officials of the Ministry (political appointments)

20. Key Obstacles: The Red Tape The process at the National level: • For non-pharmacological technologies (diagnostic or therapeutic), decisions on coverage must be approved by the National Health Board • National Health Board • Minister of Health • Regional Ministers of Health (17) • Senior officials of the Ministry (political appointments) • Committee for Coverage of Health Technologies • Politically appointed members (56, from national and regional health ministries) • Members can send subordinate (attendees vary) • Meeting agenda and docs provided 48 hrs. before meeting

21. Key Obstacles: The Red Tape The process at the National level: • For non-pharmacological technologies (diagnostic or therapeutic), decisions on coverage must be approved by the National Health Board • National Health Board • Minister of Health • Regional Ministers of Health (17) • Senior officials of the Ministry (political appointments) • Committee for Coverage of Health Technologies • Politically appointed members (56, from national and regional health ministries) • Members can send subordinate (attendees vary) • Meeting agenda and docs provided 48 hrs. before meeting • Health Technology AssessmentAgencies • Five HTA agencies in Spain • + Several regions with additional “micro”-versions (“Assessment services”) • + One Directoriate in each of the 17 regions • ?

22. Key Obstacles: The Red Tape The process at the National level: • For non-pharmacological technologies (diagnostic or therapeutic), decisions on coverage must be approved by the National Health Board • Reports from HTA Agencies may or may not be requested by political entities • National Health Board • Minister of Health • Regional Ministers of Health (17) • Senior officials of the Ministry (political appointments) • Conclusions may or may not be taken on board • Most reports, of poor quality (not peer-reviewed, not published) • Committee for Coverage of Health Technologies • Politically appointed members (56, from national and regional health ministries) • Members can send subordinate (attendees vary) • Meeting agenda and docs provided 48 hrs. before meeting • Reports remain confidential (undisclosed) • Technical reports … or post hoc alibis for non-evidence based decisions? • Health Technology AssessmentAgencies • Five HTA agencies in Spain • + Several regions with additional “micro”-versions (“Assessment services”) • + One Directoriate in each of the 17 regions • ?

23. Key Obstacles: The Red Tape Examples of rationale offered in some regions for delaying NRT: • “If NRT reduces the need for • surgery, it could vex orthopedic surgeons” • (satisfaction among physicians: 92.5% • -Gac Sanit 2004;18:275-86-) • “We cant implement this technology: it would reveal that the process we used for implementing the rest, is inadequate” “We should repeat the RCTs here, before applying this technology in our region” • “Never innovate in times of crisis” • “We can’t • afford this technology” • (it costs 30% of the net savings it generates –Spine 2002;27:1149-1159-) • “The evidence is robust, but none of the private providers in this community would benefit from implementing this technology” (net saving per inhabitant per year: 3€ –Spine 2002;27:1149-1159-) ”Have a think about whether we can set up a franchise for this technology together, in the public hospitals of this region” • “The evidence is clearly in favor, so we will implement this technology … once someone else does it first”

24. Key Obstacles: The Red Tape Examples of rationale offered in some regions for delaying NRT: • “If NRT reduces the need for • surgery, it could vex orthopedic surgeons” • (satisfaction among physicians: 92.5% • -Gac Sanit 2004;18:275-86-) • “We cant implement this technology: it would reveal that the process we used for implementing the rest, is inadequate” “We should repeat the RCTs here, before applying this technology in our region” • “Never innovate in times of crisis” • “We can’t • afford this technology” • (it costs 30% of the net savings it generates –Spine 2002;27:1149-1159-) • “The evidence is robust, but none of the private providers in this community would benefit from implementing this technology” (net saving per inhabitant per year: 3€ –Spine 2002;27:1149-1159-) ”Have a think about whether we can set up a franchise for this technology together, in the public hospitals of this region” • “The evidence is clearly in favor, so we will implement this technology … once someone else does it first”

25. Key Obstacles: The Red Tape Examples of rationale offered in some regions for delaying NRT: • “If NRT reduces the need for • surgery, it could vex orthopedic surgeons” • (satisfaction among physicians: 92.5% • -Gac Sanit 2004;18:275-86-) • “We cant implement this technology: it would reveal that the process we used for implementing the rest, is inadequate” “We should repeat the RCTs here, before applying this technology in our region” • “Never innovate in times of crisis” • “We can’t • afford this technology” • (it costs 30% of the net savings it generates –Spine 2002;27:1149-1159-) • “The evidence is robust, but none of the private providers in this community would benefit from implementing this technology” (net saving per inhabitant per year: 3€ –Spine 2002;27:1149-1159-) ”Have a think about whether we can set up a franchise for this technology together, in the public hospitals of this region” • “The evidence is clearly in favor, so we will implement this technology … once someone else does it first”

26. Key Obstacles: The Red Tape Rationale offered at the National level for delaying NRT: • “Authorization to use surgical staples on open wounds exists, but no authorization has been issued for use of staples on healthy skin” • Spanish Ministry of Health, 2011 • Evidence on safety and effectiveness: • Med Clin (Barc) 1993; 101: 570-5, Spine 1997;22:786-97 Spine 2002;27: 1149-1159, Cochrane Database of Systematic Reviews 2004;2: CD003009, Eur Spine J 2006;15:S192-299, Gac Sanit 2004;18:275–86 , Health Policy 2006; 79:345-357, IX Intnal Forum on LBP Research 2007, Spine 2007;32:1621-1628

27. Lessons learned from the NRT case: Assessing and implementing Health Technologies • It is feasible for a non-pharmacological tecnology to be: • Rigorously assessed (step-by-step process) But, in practice, all of the above is useless if… The law is irrational or disregards patients’ and taxpayers’ interests Decision-makers lack the skills needed to make decisions • Implemented successfully in clinical routine practice, as long as: • Application conditions are consistent with those in which it was assessed • Post-implementation surveillance is implemented from the start • Feasibility is test-piloted before implementation in routine practice • Following this process leads to positive (health and economic) results in clinical practice

28. Improving the translation of research into practice Aspects on which researchers can act • RCTs: Reject RCTs if they are clinically useless or misleading e.g.: • Low quality • Focusing on inappropriate comparisons (e.g., comparative effectiveness of procedures when neither has shown to be better than sham) • SRs: • Prioritize clinical usefulness over academic interest or personal CV: • Bring on board clinical wisdom (unbiased clinicians without vested interests) • It is normal that future research will nuance or change conclusions: • “Nuances” to be addressed by further research, should not be used as an excuse for holding back evidence-based, applicable conclusions Applicable conclusions based on the “best evidence which is available now”, is better than waiting for “perfect evidence” in an utopian world • Improve organizational efficiency (e.g. 3 years for reviewing 3 RCTs) • Be consistent, avoid double standards (e.g. scarring, practitioners’ training)

29. Thank you! Dr. D. Francisco M. Kovacs Red Española de Investigadores en Dolencias de la Espalda (REIDE) Fundación Kovacs www.REIDE.org www.kovacs.org