Conflicting results Vertos II versus Sham studies What to do next P LOhle

Transcript

1. Conflicting results: Vertos II versus Sham studies What to do next? Paul N.M. Lohle St. Elisabeth Hospital, Tilburg, The Netherlands Paris 2011 10 min.
2. Recent RCTs provide conflicting results • Two Sham studies showed no benefit of PV • Vertos II study found effective pain relief after PV at acceptable costs. Kallmes DF, Comstock BA, Heagerty PJ et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009; 361(6):569-579. Buchbinder R, Osborne RH, Ebeling PR et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med 2009; 361(6):557-568 Klazen CA, Lohle PN, et al. Lancet. 2010 Sep 25;376(9746):1085-92.
3. • two “ blinded ” studies; comparing 2 groups PV Sham • neelde + cement ↔ neelde + longacting local anesthetic - PMMA - bupivacaina - marcaïne Concluded: - There is no statistically significant difference between patients treated with PV or the Sham procedure. - It is therefore inappropriate to offer this treatment in routine care. 2 Sham studies New Engl J Med
4. 2 Sham studies (New Engl J Med) I believe; • mixed “apples with pears” • statistical en methodologic flaws – included mix subacute + chronic fractures – no control group without intervention – absence of bone edema on MRI as a consistent inclusion criterium , which makes these 2 studies difficult to interpret clinically
5. Vertos II Randomised Controlled Trial • 6 hospitals participating • referred by the general practitioner for back pain • all patients completed a clinical questionnaire • all patients underwent a physical examination • patients randomised to PV or conservative therapy
6. Vertos II: strict inclusion criteria • VCF on spine X-ray • local back pain ≤ 6 weeks • local back pain VAS score ≥ 5 • VCF with bone edema on MRI • osteoporosis • age ≥ 50 years
7. Vertos II patients 202 101 101 Percutaneous Vertebroplasty Conservative Therapy
8. Baseline No differences between groups
9. Endpoints 1. Primary endpoint – VAS-score 1 month and 1 year 2. Secondary endpoint – cost effectiveness 1 month and 1 year – secondary VCFs during 1 year follow up 3. Third endpoint – quality of life (QUALEFFO)
10. 1. Primary endpoint: pain relief
11. Results VAS-score 1 month (significant VAS score difference 2.6) 1 year (significant VAS score difference 2.0)
12. Results Kaplan-Meier curve • Kaplan-Meier shows significant pain relief (decrease in VAS score >3) achieved earlier and in more patients after PV compared to conservative therapy chronic pain 1 year follow up
13. 2a. Secondary endpoint: cost-effectiveness
14. Cost-effectiveness • Although PV is more expensive than CT with a difference in total costs - at 1 month € 2,474 - at 1 year € 2,450 • However, significant difference in QALYs gained in favor of PV • This results in, cost-effectiveness ratio at 1 year of €22,685 per QALY gained → very much acceptable in the “Western world”
15. 2B. Secondary endpoint: secondary VCFs after PV
16. Secondary VCFs (height loss > 20% or ≥ 4 mm) • There is no significant difference between groups at 1 year follow-up. • If any, there were fewer fractures after PV; – 16% secondary # after PV – 25% secondary # with conservative therapy PV conservative therapy p -value 1 year 14/91 pt 16 % 20/85 pt 25% 0.28
17. Already existing fractures • Significant further height loss of the treated VCF in the conservative group. PV Conservative therapy P-value 1 year 11/91 pts 12% 35/85 pts 41% ≤ 0.001 PV protects against further height loss of treated vertebral bodies, PV protects stature, pumonary function and clinical outcome on long term
18. 3a+b. Third endpoints: - quality of life - function
19. Quality of life: QUALEFFO Quicker and better quality of life after PV (p<0.001)
20. Physical function: Roland Morris Disability score Quicker and better physical function after PV (p<0.001)
21. Vertos II concludes: • In a selected subgroup of patients with an acute osteoporotic VCF and ungoing pain, PV is effective and safe. • Pain relief after PV is immediate, sustained during one year and significant better compared to conservative therapy, at acceptable costs.
22. Vertos II versus Sham • Vertos II, is a much more pragmatic study provides the clinician with directly applicable information on how to best treat the patient. • 2 Sham studies, lacked a control group without intervention and the best treatment option remains unclear for the clinician.
23. The battle continues • Sham studies, New Engl J Med → harm and damage • Vertos II, The Lancet → showed the power of PV • but it is not enough, since – Evidence Based Medicine demands high level of evidence – Health Insurance Companies know how to abuse it… • There is a difference in Level of Evidence between – two Sham studies = 1a level of evidence – Vertos II = 1b level of evidence we have to act again…
24. Help, all hands on deck • physicians contacted the health insurances to convince them to continue to reimburse PV • authors submitted letters to the editor and commentaries about the Sham studies and Vertos II – Gangi + Clark – Anselmetti – Murphy – Waldlaw + Van Meirhaeghe – Toms ,……………..critical views and comments. • but I believe, the only real solution to the problem is… to obtain Level of Evidence : 1a
25. Level of Evidence 1a !! new study: – Sham study (study by Kallmes) – Vertos II strict inclusion criteria (study by Klazen, Vertos IV) Kallmes Klazen
26. Level of Evidence 1a !! new study: – Sham study (study by Kallmes) – Vertos II strict inclusion criteria (study by Klazen, Vertos IV) MIX Kallmes Klazen
27. Level of Evidence 1a !! new study: – Sham study (study by Kallmes) – Vertos II strict inclusion criteria (study by Klazen, Vertos IV) MIX Vertos IV Kallmes Klazen
28. Vertos IV Objective • to compare pain relief after PV versus the Sham intervention in selected patients with an acute osteoporotic VCF using the strict inclusion criteria as in Vertos II. • osteoporotic VCF, VAS score > 5 • local back pain < 6 weeks • bone edema on MRI Vertos IV ! randomized for PV or Sham intervention
29. provide Level of Evidence 1a • Randomised sham controlled multicenter study + strict inclusion criteria – Australia (1) – The Netherlands (4) • Financial support come from Dutch government + Company • The sample size calculated (using G-Power) – 142 patients are required for this study – we assume a withdrawal rate of 20% – 180 patients will be enrolled, 90 in each group. – conform Kallmes we expect a 1.5 point difference in pain relief, measured by VAS score. Vertos IV
30. Vertos IV • already approved by the METC • start March 2011 • expect enrollment 180 patients in 1 year (5 centers) • believe first publication in 2-3 years I hope to share with you our preliminary results much sooner, next year, here at this symposium in Paris! more information on Vertos IV in Trial registration http://www.clinicaltrials.gov September 2010 Vertos IV
31. Vertos IV • already approved by the METC • start March 2011 • expect enrollment 180 patients in 1 year (5 centers) • believe first publication in 2-3 years I hope to share with you our preliminary results much sooner, next year, here at this symposium in Paris! more information on Vertos IV in Trial registration http://www.clinicaltrials.gov September 2010 Thank you for your attention Vertos IV