HTA: Models, Costs & Benefits.

Transcription

1 HTA: Models, Costs & Benefits

2 Explicit evaluation of costs and benefits Advantages Potential for more consistent decision making Potential for more transparent decision making Facilitates increasing the benefit obtained from scarce resources Difficult (if not impossible) to capture everything that might be relevant to a particular decision Availability of alternative treatments, innovative nature of technology Ultimately an act of faith Cannot prove that explicit consideration of costs and benefits leads to better decisions (cannot observe the counterfactual)

3 Incremental Cost-Effectiveness Ratio ICER = COST new - COST old QALY new - QALY old QALYs (Quality-adjusted life-years) are estimated by weighting the time individuals spend in different health states, using health state utility values as weights.

4 Pharmacological success story & decision making challenge HCV identified in 1989, Interferon (approved 1991), Ribavirin+IFN (approved 1998), Pegylated IFN (approved 2001) Telaprevir & Boceprevir (approved 2011) Sofosbuvir & Simeprevir (approved 2013) More than 30 direct acting antiviral agents in clinical trials, e.g. sofosbuvir + ledipasvir paritaprevir + ritonavir + ombitasvir + dasabuvir asunaprevir + daclatasvir +/- non-nucleoside polymerase inhibitor

5 Hepatitis C virus infection A slowly progressive disease of the liver Effects range from asymptomatic or mild disease (80%) to liver failure or primary liver cancer Hepatitis C virus has at least 6 genotypes with many subtypes Genotype pattern varies across countries e.g. England GT1 (46%) GT2 (~5%) GT3 (43%) GT4, 5 & 6 combined (~5%) Main aim of treatment to achieve Sustained Virological Response (SVR) e.g. SVR12 undectable HCV RNA in serum 12 weeks after treatment

6 Current UK clinical practice GT1 Telaprevir+PegIFN+ribavirin (24-48 wks, response-guided) Boceprevir+PegIFN+ribavirin (24-48 wks, response-guided) PegIFN+ribavirin (24 or 48 wks, response-guided) GT4 PegIFN+ribavirin (24 or 48 wks, response-guided) HIV co-infection (any GT) PegIFN+ribavirin (48 wks) Telaprevir+PegIFN+ribavirin (for GT1) Boceprevir+PegIFN+ribavirin (for GT1)

7 Decision problem Population Intervention Comparators Outcomes Adults with chronic hepatitis C Sofosbuvir + pegifn alfa + ribavirin Sofosbuvir + ribavirin PegIFN + ribavirin Telaprevir + pegifn alfa + ribavirin (GT1 only) Boceprevir + pegifn alfa + ribavirin (GT1 only) Best supportive care sustained virological response mortality adverse effects of treatment health-related quality of life

8 Incremental Cost-Effectiveness Ratio ICER = COST SPR - COST PR QALY SPR - QALY PR QALYs (Quality-adjusted life-years) are estimated by weighting the time individuals spend in different health states, using health state utility values as weights. COST is estimated from a combination the cost of treatment and healthcare costs associated with time spent in different health states.

9 Economic model SVR cirrhosis SVR noncirrhotic Noncirrhotic Compensated cirrhosis Hepatocellular carcinoma Decompensated cirrhosis Excess mortality Liver transplant Post-liver transplant

10 Transition Probabilities SVR from sofosbuvir trials and historical controls: NEUTRINO sof+pr (12w) single arm, open label N=327 FISSION sof+r (12w) vs. PR (24w) N=499 FUSION sof+r (12w) vs. sof+r (16w) N=201 POSITRON sof+r vs. placebo N=278 VALENCE sof+r single arm, open label N = 334 Transition probabilities (from literature): non-cirrhotic compensated cirrhosis compensated cirrhosis decompensated cirrhosis decompensated cirrhosis hepatocellular carcinoma decompensated cirrhosis liver transplant etc.

11 Drug costs per treatment regimen Treatment regimen (wks) Protease Inhibitor cost ( ) PegIFN cost ( ) Ribavirin cost ( ) Total drugs cost ( ) Sofosbuvir12+PR12 34,938 1, ,379 Sofosbuvir12+R12 34, ,813 Sofosbuvir24+R24 69,966 1,751 71,717 Tel12+PR48 22,398 6,266 3,503 32,166 Boc24+PR28 16,800 3,655 2,043 22,498 PR24 3,133 1,751 4,884 PR48 6,266 3,503 9,769 Note telaprevir & boceprevir costs may vary as a result of Response Guided Therapy 11

12 Health state costs SVR F0-F3 343 SVR F4 753 F0-F2 183 F3 949 F4 1,506 Decompensated Cirrhosis Hepatocellular carcinoma 12,069 10,755 Liver transplant 48,685 Post liver transplant 1,833 Wright et al Longworth et al Literature based health state costs widely used in HTAs of HepC treatments 12

13 Health State Utility Values Non-cirrhotic HCV 0.77 Mild Hep C trial (n=185) + Observational study A (n=71) Compensated cirrhosis 0.55 Observational study A (n=40) Treatment for mild HCV xxx SF-6D utility decrement from Sofosbuvir trials &EQ- Treatment for moderate HCV xxx 5D decrements from literature for other treatments SVR (non-cirrhotic) 0.79 Based on mild Hep C trial (n=24) SVR (cirrhotic) 0.60 Observational study A (n=21) Decompensated Cirrhosis Hepatocellular carcinoma Liver transplant 0.45 Observational liver transplant study Patients who were listed for transplant were a mix of DC and HCC (n=64). Post liver transplant 0.67 Observational liver transplant study. Three months after transplant (n=147) not all Hep C patients. 13

14 Estimated cost per QALY gained GT1 GT2 GT3 GT456 IFN elegible IFN unsuitable TN 15,000 49,000 TE 13,000 TN 46,000 8,000 TE 10,000 9,000 TN 21,000 w/o cirrhosis cirrhosis 21,000 w/o cirrhosis cirrhosis TE 9,000 29,000 w/o cirrhosis cirrhosis TN 27,000 TE Not Recommended Recommended

15 Conclusions This example is towards the more complex end of the spectrum because of the many genotypes & whether someone is treatment naïve or experienced Data drawn from a wide range of sources (with implications for how relevant information is identified & assessed) The apparently very high cost of the new treatment is seen in the context of healthcare costs over the patient s lifetime Note how the HTA in this case provides a basis for decision making across subgroups Depending on how the decision making process is organised there is the potential for considerable transparency regarding the decisions to recommend or not recommend treatment, and potential for decisions to be contested