Appendix E: PSA Parameters

Variable / Mean Value / SE / Parameterisation / Distribution used
ACR response rates / Individual treatment response rate / n/a / Use N*100=alpha of the one parameter Gamma distribution for each ACR category / Dirichlet
HAQ score adjustments (initial improvement) / Non-responder / 0.14 / 0.02 / Taken from post-hoc analysis of OPTION, LITHE and TOWARD [3-5] (see Appendix A) / Normal
ACR20 responder / 0.46 / 0.02
ACR50 responder / 0.68 / 0.03
ACR70 responder / 0.9 / 0.03
Long term changes: HAQ progression / bDMARD / 0 / 0.0057 / Assume 0.0225 (sDMARD value) is the upper limit of CI and 0 is the mean value in the acceptable range / Normal
sDMARD / 0.0225 / 0.0019 / Assume 0.03 (palliative care) is the upper limit of CI and 0.0225 is the mean value in the acceptable range
Palliative care / 0.03 / n/a / Linked to sDMARD value / Use lognormal on the difference with sDMARD HAQ progression: 1.33
Rebound effect / 1 / n/a / Assumption +/-20% / Uniform [0.8, 1.2]
VAS pain score / Baseline / 75.00 / 1.26 / Alpha and beta parameters calculated using mean value and SE reported in Hyrich 2009 [1] / Beta
(Generated probabilistic value is multiplied by 100)
Non-responder / 4.02 / 0.79 / Alpha and beta parameters calculated using mean value and SE taken from OPTION, LITHE and TOWARD [3-5] (see Appendix A)
ACR20 responder / 23.97 / 0.86
ACR50 responder / 36 / 0.95
ACR70 responder / 45.96 / 1.26
Palliative care / 55 / 1.2755 / Results of clinician survey Assume the CI is between 50-60
Mortality / Mortality risk / 1.33 / 0.1304 / Wolfe et al. 1994 [2] / Lognormal
Cost / Outpatient visit (first attendance) / 214 / 5.91 / Based on NHS reference costs [7] / Normal
Outpatient visit (subsequent), GP visit, Full blood count, ESR, LFT, U&E , Chest X-ray tests / n/a / n/a / Values not sampled independently but linked to outpatient visit sample / n/a
Inpatient cost / 240 / 48.00 / CIs are derived by assuming lower and upper limits are ±20% of the mean value / Lognormal
Infusion administration / 171 / 34.27
Home visit / 27 / 5.40
Proportion of patients that require a nurse visit for subcutaneous injection / 0.1 / 0.02 / Beta
Average annual income of the population (indirect cost) / 26989 / 2698.90 / CIs are derived by assuming lower and upper limits are ±10% of the mean value / Lognormal
AE (pneumonia) / 2047 / 37.26 / Based on NHS reference costs [7] / Normal
AE (palliative care) / 314.17 / 62.83 / CIs are derived by assuming lower and upper limits are ±20% of the mean value / Lognormal
AE disutility / bDMARDs / 0.986 / 0.0036 / Assumes upper limit of CI=1 (no disutility), and the respective mean is used to create an acceptable range. / Beta
sDMARDs / 0.970032841 / 0.0076
Palliative care / 0.970032841 / 0.0076
AE event probabilities / Certolizumab pegol / 0.113 / 0.0742 / Singh et al. 2012 [6] / Beta
bDMARD (excluding certolizumab pegol) / 0.035 / 0.0048
Treatment Discontinuation / Discontinuation (Loglogistic model) / 0 / 1 / Based on the variance covariance derived from treatment discontinuation analysis (Appendix B) / Multinomial Normal

ACR, American College of Rheumatology; AE, adverse event; American College of Rheumatology, ACR; bDMARDs, biologic disease modifying anti-rheumatic drug; CI, confidence interval; ESR, erythrocyte sedimentation rate; GP, general practitioner; HAQ, Health Assessment Questionnaire; LFT, liver function test; N, sample size; n/a, not applicable; sDMARD, synthetic disease modifying anti-rheumatic drug; U&E , urea and electrolytes; VAS, visual analogue scale

References

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2 Wolfe F. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994;37(4):481-94.

3 Fleischmann RM, Halland AM, Brzosko M, et al. Tocilizumab inhibits structural joint damage and improves physical function in patients with rheumatoid arthritis and inadequate responses to methotrexate: LITHE study 2-year results. J Rheumatol. 2013 Feb;40(2):113-26.

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5 Smolen JS, Beaulieu A, Rubbert-Roth A et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008 Mar 22;371(9617):987-97.

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7 NHS reference costs 2010/2011. Department of Health. (2011, January 13). Publications policy and guidance. Retrieved March 1, 2012, from Department of Health: