Abstract
This paper presents a practical approach to analyzing incomplete quality of life (QOL) data that contains non-ignorable dropouts in patients with advanced non-small-cell lung cancer (NSCLC). QOL scores for the physical domain at baseline and at the end of the first and second courses of chemotherapy were compared between two treatment groups in a phase III trial. One hundred and 103 eligible patients were randomized to receive cisplatin and irinotecan (CPT-P) or cisplatin and vindesine, respectively; of those two groups, 83 and 85, respectively, completed a QOL questionnaire at least at baseline. A multiple imputation incorporating auxiliary QOL variables was implemented as one of alternatives of sensitivity analyses; these were complete case, available case, and pattern mixture analyses. Although larger sensitivity to missing data was found for CPT-P treatment, none of the alternative analyses demonstrated a significant difference in estimated slopes over time between the groups. This study presents an analytical approach for dealing with the complex problem of missing QOL data. It must be noted, however, that the validity of the multiple imputation method we present is not certain unless we can specify sufficiently informative auxiliary variables to ensure the conversion of non-ignorable missingness to ignorable.
Similar content being viewed by others
Abbreviations
- ABB:
-
approximate Bayesian bootstrap
- CPT-P:
-
cisplatin + irinotecan
- ECOG:
-
Eastern Cooperative Oncology Group
- MAR:
-
missing at random
- MCAR:
-
missing completely at random
- MI:
-
multiple imputation
- MNAR:
-
missing not at random
- NSCLC:
-
non-small-cell lung cancer
- PM:
-
pattern mixture
- PS:
-
performance status
- QOL:
-
quality of life
- QOL-ACD:
-
Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs
- VDS-P:
-
cisplatin + vindesine
References
A Bottomley F Efficace R Thomas V Vanvoorden SH. Ahmedzai (2003) ArticleTitleHealth-related quality of life in non-small-cell lung cancer: Methodologic issues in randomized controlled trials J Clin Oncol. 21 2982–2992 Occurrence Handle10.1200/JCO.2003.01.203 Occurrence Handle12885819
C Gridelli F Perrone F Nelli S Ramponi F. De Marinis (2001) ArticleTitleQuality of life in lung cancer patients Ann Oncol. 12 IssueIDSuppl 3 S21–S25 Occurrence Handle10.1023/A:1013034729575
J Klastersky M. Paesmans (2001) ArticleTitleResponse to chemotherapy, quality of life benefits and survival in advanced non-small cell lung cancer: review of literature results Lung Cancer. 34 IssueIDSuppl 4 S95–S101 Occurrence Handle10.1016/S0169-5002(01)00383-X
M Ranson N Davidson M Nicolson et al. (2000) ArticleTitleRandomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer J Natl Cancer Inst. 92 1074–1080 Occurrence Handle10.1093/jnci/92.13.1074 Occurrence Handle1:CAS:528:DC%2BD3cXlsVChurc%3D Occurrence Handle10880550
K Kelly J Crowley PA Bunn SuffixJr et al. (2001) ArticleTitleRandomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non–small-cell lung cancer: A Southwest Oncology Group trial J Clin Oncol. 19 3210–32118 Occurrence Handle1:CAS:528:DC%2BD3MXltlShtb4%3D Occurrence Handle11432888
CM Moinpour J Sawyers Triplett B McKnight et al. (2000) ArticleTitleChallenges posed by non-random missing quality of life data in an advanced-stage colorectal cancer clinical trial Psychooncology. 9 340–354 Occurrence Handle10.1002/1099-1611(200007/08)9:4<340::AID-PON466>3.3.CO;2-6 Occurrence Handle1:STN:280:DC%2BD3cvjsValtg%3D%3D Occurrence Handle10960931
T Conroy H Bleiberg B. Glimelius (2003) ArticleTitleQuality of life in patients with advanced colorectal cancer: What has been learnt? Eur J Cancer. 39 287–294 Occurrence Handle10.1016/S0959-8049(02)00664-0 Occurrence Handle1:STN:280:DC%2BD3s%2Fls1SgsA%3D%3D Occurrence Handle12565979
DL Fairclough DD Gagnon MJ Zagari N Marschner M. Dicato (2003) ArticleTitleEpoetin Alfa Study Group Evaluation of quality of life in a clinical trial with nonrandom dropout: The effect of epoetin alfa in anemic cancer patients. Qual Life Res. 12 1013–1027 Occurrence Handle10.1023/A:1026116426494 Occurrence Handle1:STN:280:DC%2BD3srmtlOntg%3D%3D Occurrence Handle14651419
CM Moinpour B Lyons PK Grevstad et al. (2002) ArticleTitleQuality of life in advanced non-small-cell lung cancer: Results of a Southwest Oncology Group randomized trial Qual Life Res. 11 115–126 Occurrence Handle10.1023/A:1015048908822 Occurrence Handle1:STN:280:DC%2BD383nvVWhsw%3D%3D Occurrence Handle12018735
J Bernhard DF Cella AS Coates et al. (1998) ArticleTitleMissing quality of life data in cancer clinical trials: Serious problems and challenges Stat Med. 17 517–532 Occurrence Handle10.1002/(SICI)1097-0258(19980315/15)17:5/7<517::AID-SIM799>3.3.CO;2-J Occurrence Handle1:STN:280:DyaK1c3htV2ksg%3D%3D Occurrence Handle9549801
RJ Simes V Greatorex VJ. Gebski (1998) ArticleTitlePractical approaches to minimize problems with missing quality of life data Stat Med. 17 725–737 Occurrence Handle10.1002/(SICI)1097-0258(19980315/15)17:5/7<725::AID-SIM817>3.3.CO;2-T Occurrence Handle1:STN:280:DyaK1c3htV2rug%3D%3D Occurrence Handle9549819
RA Little DB. Rubin (2002) Statistical Analysis with Missing Data, Second edn Wiley New York. 3–23
DL. Fairclough (2002) Design and Analysis of Quality of Life Studies in Clinical Trials Chapman & Hall/CRC New York 41–181
DL Fairclough HF Peterson D Cella P. Bonomi (1998) ArticleTitleComparison of several model-based methods for analysing incomplete quality of life data in cancer clinical trials Stat Med. 17 781–796 Occurrence Handle10.1002/(SICI)1097-0258(19980315/15)17:5/7<781::AID-SIM821>3.3.CO;2-F Occurrence Handle1:STN:280:DyaK1c3htV2qsA%3D%3D Occurrence Handle9549823
DK Pauler S McCoy C. Moinpour (2003) ArticleTitlePattern mixture models for longitudinal quality of life studies in advanced stage disease Stat Med. 22 795–809 Occurrence Handle10.1002/sim.1397 Occurrence Handle12587106
Y. Matsuyama (2003) ArticleTitleSensitivity analysis for the estimation of rates of change with non-ignorable drop-out: An application to a randomized clinical trial of the vitamin D3 Stat Med. 22 811–827 Occurrence Handle10.1002/sim.1367 Occurrence Handle12587107
DB. Rubin (1987) Multiple Imputation for Nonresponse in Surveys Wiley New York.
PW Lavori R Dawson D. Shera (1995) ArticleTitleA multiple imputation strategy for clinical trials with truncation of patient data Stat Med. 14 1913–1925 Occurrence Handle1:STN:280:BymD1M%2Fntlw%3D Occurrence Handle8532984
J Barnard XL. Meng (1999) ArticleTitleApplications of multiple imputation in medical studies: From AIDS to NHANES Stat Meth Med Res. 8 17–36 Occurrence Handle10.1191/096228099666230705 Occurrence Handle1:STN:280:DyaK1M3nslajtA%3D%3D
JL. Schafer (1999) ArticleTitleMultiple imputation: A primer Stat Meth Med Res. 8 3–15 Occurrence Handle1:STN:280:DyaK1M3nslajtw%3D%3D
DL. Fairclough (2002) Multiple imputation for non-random missing data in longitudinal studies of health-related quality of life M Mesbah BF Cole MLT. Lee (Eds) Statistical Methods for Quality of Life Studies. Kluwer Academic Publishers Boston 323–337
M Kurihara H Shimizu K Tsuboi et al. (1999) ArticleTitleDevelopment of quality of life questionnaire in Japan: Quality of life assessment of cancer patients receiving chemotherapy Psycho-Oncology. 8 355–363 Occurrence Handle1:STN:280:DyaK1MvgsVWjsw%3D%3D Occurrence Handle10474853
T Matsumoto Y Ohashi S Morita et al. (2002) ArticleTitleQOL questionnaire for cancer patients treated with anticancer drugs (QOL-ACD): Validity and reliability in Japanese patients with advanced non-small-cell lung cancer Qual Life Res. 11 483–493 Occurrence Handle1:STN:280:DC%2BD38zmvVyksg%3D%3D Occurrence Handle12113395
NM Laird JH. Ware (1982) ArticleTitleRandom-effects models for longitudinal data Biometrics. 38 963–974 Occurrence Handle1:STN:280:BiyC2sbhs1Q%3D Occurrence Handle7168798
PR Rosenbaum DB. Rubin (1983) ArticleTitleThe central role of the propensity score in observational studies for causal effects Biometrika. 70 41–55
NK Aaronson S Ahmedzai B Bergman et al. (1993) ArticleTitleThe European Organization for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology J Natl Cancer Inst. 85 365–376 Occurrence Handle1:STN:280:ByyC28vivVc%3D Occurrence Handle8433390
JE Herndon SuffixII S Fleishman MP Kosty MR. Green (1997) ArticleTitleA longitudinal study of quality of life in advanced non-small cell lung cancer: Cancer and Leukemia Group B (CALGB) 8931 Control Clin Trials. 18 286–300 Occurrence Handle1:CAS:528:DyaK2sXmtFGqtL4%3D Occurrence Handle9257067
K Kobayashi F Takeda S Teramukai et al. (1998) ArticleTitleA cross-validation of the European organization for research and treatment of cancer QLQ-C30 (EORTC QLQ-C30) for Japanese with lung cancer Eur J Cancer. 34 810–815 Occurrence Handle1:STN:280:DyaK1M%2FhsVChtg%3D%3D Occurrence Handle9797690
S Morita K Kobayashi K Eguchi et al. (2003) ArticleTitleInfluence of clinical parameters on quality of life during chemotherapy in patients with advanced non-small cell lung cancer: application of a general linear model Jpn J Clin Oncol. 33 470–476 Occurrence Handle14594941
I Kopp W Lorenz M Rothmund M. Koller (2003) ArticleTitleRelation between severe illness and non-completion of quality-of-life questionnaires by patients with rectal cancer J R Soc Med. 96 442–428 Occurrence Handle12949200
JM. Lachin (2000) ArticleTitleStatistical considerations in the intent-to-treat principle Control Clin Trials. 21 167–189 Occurrence Handle1:STN:280:DC%2BD3c3otlCqtA%3D%3D Occurrence Handle10822117
B.F Cole K.L. Kilbridge (2002) Quality-adjusted survival analysis in cancer clinical trials M Mesbah BF Cole MLT. Lee (Eds) Statistical Methods for Quality of Life Studies. Kluwer Academic Publishers Boston 287–300
DB. Rubin (1998) ArticleTitleMore powerful randomization-based p-values in double-blind trials with non-compliance Stat Med. 17 371–385 Occurrence Handle1:STN:280:DyaK1c7lsVeisw%3D%3D Occurrence Handle9493260
CE Frangakis DB. Rubin (2002) ArticleTitlePrincipal stratification in causal inference Biometrics. 58 21–29 Occurrence Handle11890317 Occurrence HandleMR1891039
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Morita, S., Kobayashi, K., Eguchi, K. et al. Analysis of incomplete quality of life data in advanced stage cancer: A practical application of multiple imputation. Qual Life Res 14, 1533–1544 (2005). https://doi.org/10.1007/s11136-004-7708-x
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11136-004-7708-x