Extrapolation of Survival Curves from Cancer Trials Using External Information.
Estimates of life expectancy are a key input to cost-effectiveness analysis (CEA) models for cancer treatments. Due to the limited follow-up in Randomized Controlled Trials (RCTs), parametric models are frequently used to extrapolate survival outcomes beyond the RCT period. However, different parametric models that fit the RCT data equally well may generate highly divergent predictions of treatment-related gain in life expectancy. Here, we investigate the use of information external to the RCT data to inform model choice and estimation of life expectancy.



We used Bayesian multi-parameter evidence synthesis to combine the RCT data with external information on general population survival, conditional survival from cancer registry databases, and expert opinion. We illustrate with a 5-year follow-up RCT of cetuximab plus radiotherapy v. radiotherapy alone for head and neck cancer.



Standard survival time distributions were insufficiently flexible to simultaneously fit both the RCT data and external data on general population survival. Using spline models, we were able to estimate a model that was consistent with the trial data and all external data. A model integrating all sources achieved an adequate fit and predicted a 4.7-month (95% CrL: 0.4; 9.1) gain in life expectancy due to cetuximab.



Long-term extrapolation using parametric models based on RCT data alone is highly unreliable and these models are unlikely to be consistent with external data. External data can be integrated with RCT data using spline models to enable long-term extrapolation. Conditional survival data could be used for many cancers and general population survival may have a role in other conditions. The use of external data should be guided by knowledge of natural history and treatment mechanisms.
School of Social and Community Medicine, University of Bristol, Bristol, UK (PG, AED, NJW).|Mapi, Houten, the Netherlands (PG).
Patricia
P
Guyot
School of Social and Community Medicine, University of Bristol, Bristol, UK (PG, AED, NJW).
Anthony E
AE
Ades
Bristol Haematology and Oncology Centre, Bristol, UK (MB).
Matthew
M
Beasley
Gustave Roussy, Université Paris-Saclay, Service de biostatistique et d'épidémiologie / Ligue Nationale Contre le Cancer meta-analysis plateform, F-94805 Villejuif, France (BL, JP).|Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, F-94085 Villejuif, France (BL, JP).
Béranger
B
Lueza
Gustave Roussy, Université Paris-Saclay, Service de biostatistique et d'épidémiologie / Ligue Nationale Contre le Cancer meta-analysis plateform, F-94805 Villejuif, France (BL, JP).|Université Paris-Saclay, Univ. Paris-Sud, UVSQ, CESP, INSERM, F-94085 Villejuif, France (BL, JP).
Jean-Pierre
JP
Pignon
School of Social and Community Medicine, University of Bristol, Bristol, UK (PG, AED, NJW).
Nicky J
NJ
Welton
D000367:Age Factors; D001499:Bayes Theorem; D003362:Cost-Benefit Analysis / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000628:therapy; D006801:Humans; D015233:Models, Statistical; D009369:Neoplasms / Q000401:mortality* / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D018426:SEER Program; D012737:Sex Factors; D016019:Survival Analysis
cost-effectiveness analysis; external data; extrapolation; restricted cubic splines; survival analysis
Ann Oncol. 2007 Aug;18(8):1408-13
17693654
Med Decis Making. 2013 Aug;33(6):740-2
23864435
Eur J Cancer. 2001 Sep;37 Suppl 4:S16-22
11597400
Radiother Oncol. 2011 Jul;100(1):33-40
21684027
J Natl Cancer Inst. 2007 May 16;99(10):777-89
17505073
Health Technol Assess. 2009 Jun;13 Suppl 1:49-54
19567214
Health Technol Assess. 2010 May;14(24):1-162
20492762
Health Technol Assess. 2010 May;14 Suppl 1:17-21
20507799
Cancer. 2007 Apr 1;109(7):1331-43
17326199
J Clin Oncol. 2010 May 20;28(15):2520-8
20406936
Stat Med. 2006 Jun 15;25(11):1960-75
16220511
BMC Med Res Methodol. 2011 May 06;11:61
21548941
Stat Methods Med Res. 2015 Apr;24(2):287-301
21937472
BMC Med Res Methodol. 2012 Feb 01;12:9
22297116
Int J Biostat. 2010;6(1):Article 34
21969987
Health Technol Assess. 2009 Jun;13 Suppl 1:23-8
19567210
Eur J Cancer. 2004 Feb;40(3):326-35
14746849
Health Technol Assess. 2007 Jan;11(1):1-90
17181984
J R Stat Soc Ser C Appl Stat. 2010 Mar;59(2):233-253
20383261
Stat Med. 2007 Dec 30;26(30):5486-98
17893893
Oncologist. 2003;8(6):541-52
14657533
Head Neck. 2010 Dec;32(12):1613-8
20310043
Health Technol Assess. 2004 Sep;8(37):iii, ix-xi, 1-82
15361313
Head Neck. 1998 May;20(3):250-65
9570632
Multivariate Behav Res. 2011 May;46(3):399-424
21818162
Stat Med. 2002 Aug 15;21(15):2175-97
12210632
BMJ Open. 2012 May 04;2(3):
22561354
Br J Cancer. 2003 Jul 21;89(2):232-8
12865907
Health Technol Assess. 2009 Jun;13 Suppl 1:29-33
19567211
Pharmacoeconomics. 2015 May;33(5):457-66
25616671
Value Health. 2011 Jul-Aug;14(5):640-6
21839400
Med Decis Making. 2013 Aug;33(6):743-54
23341049
Lancet. 2000 Mar 18;355(9208):949-55
10768432
N Engl J Med. 2006 Feb 9;354(6):567-78
16467544
Radiother Oncol. 2009 Jul;92(1):4-14
19446902
Stat Med. 1999 Feb 28;18(4):441-54
10070685
Oncologist. 2010;15(8):873-82
20647391