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Gepubliceerd in: Quality of Life Research 1/2008

01-02-2008

Handling missing quality of life data in HIV clinical trials: what is practical?

Auteurs: Diane L. Fairclough, Herbert Thijs, I-Chan Huang, Henrik W. Finnern, Albert W. Wu

Gepubliceerd in: Quality of Life Research | Uitgave 1/2008

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Abstract

Aims

Missing health-related quality of life (HRQOL) data in clinical trials can impact conclusions but the effect has not been thoroughly studied in HIV clinical trials. Despite repeated recommendations to avoid complete case (CC) analysis and last observation carried forward (LOCF), these approaches are commonly used to handle missing data. The goal of this investigation is to describe the use of different analytic methods under assumptions of missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR) using HIV as an empirical example.

Methods

Medical Outcomes Study HIV (MOS-HIV) Health Survey data were combined from two large open-label multinational HIV clinical trials comparing treatments A and B over 48 weeks. Inclusion in the HRQOL analysis required completion of the MOS-HIV at baseline and at least one follow-up visit (weeks 8, 16, 24, 40, 48). Primary outcomes for the analysis were change from week 0 to 48 in mental health summary (MHS), physical health summary (PHS), pain and health distress scores analyzed using CC, LOCF, generalized estimating equations (GEE), direct likelihood and sensitivity analyses using joint mixed-effects model, and Markov chain Monte Carlo (MCMC) multiple imputation. Time and treatment were included in all models. Baseline and longitudinal variables (adverse event and reason for discontinuation) were only used in the imputation model.

Results

A total of 511 patients randomized to treatment A and 473 to treatment B completed the MOS-HIV at baseline and at least one follow-up visit. At week 48, 71% of patients on treatment A and 31% on treatment B completed the MOS-HIV survey. Examining changes within each treatment group, CC and MCMC generally produced the largest or most positive changes. The joint model was most conservative; direct likelihood and GEE produced intermediate results; LOCF showed no consistent trend. There was greater spread for within-group changes than between-group differences (within MHS scores for treatment A: −0.1 to 1.6, treatment B: 0.4 to 2.0; between groups: −0.7 to 0.4; within PHS scores for treatment A: −1.5 to 0.4, treatment B: −1.7 to −0.2; between groups: 0.1 to 1.1). The size of within-group changes and between-group differences was of similar magnitude for the pain and health distress scores. In all cases, the range of estimates was small <0.2 SD (less than 2 points for the summary scores and 5 points for the subscale scores).

Conclusions

Use of the recommended likelihood-based models that do not require assumptions of MCAR was very feasible. Sensitivity analyses using auxiliary information can help to investigate the potential effect that missing data have on results but require planning to ensure that relevant data are prospectively collected.
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Literatuur
1.
go back to reference Walensky, R. P., Paltiel, A. D., Losina, E., Mercincavage, L. M., Schackman, B. R., Sax, P. E., Weinstein, M. C., & Freedberg, K. A. (2006) The survival benefits of AIDS treatment in the United States. The Journal of Infectious Diseases, 194(1), 11–19.PubMedCrossRef Walensky, R. P., Paltiel, A. D., Losina, E., Mercincavage, L. M., Schackman, B. R., Sax, P. E., Weinstein, M. C., & Freedberg, K. A. (2006) The survival benefits of AIDS treatment in the United States. The Journal of Infectious Diseases, 194(1), 11–19.PubMedCrossRef
2.
go back to reference Sax, P. E., Gathe, J. C. Jr. (2005). Beyond efficacy: The impact of combination antiretroviral therapy on quality of life. AIDS Patient Care STDS, 19(9), 563–576.PubMedCrossRef Sax, P. E., Gathe, J. C. Jr. (2005). Beyond efficacy: The impact of combination antiretroviral therapy on quality of life. AIDS Patient Care STDS, 19(9), 563–576.PubMedCrossRef
3.
go back to reference Cohen, C., Revicki, D. A., Nabulsi, A., Sarocco, P. W., & Jiang, P. (1998). A randomized trial of the effect of ritonavir in maintaining quality of life in advanced HIV disease. Advanced HIV Disease Ritonavir Study Group. AIDS, 12(12), 1495–1502.PubMedCrossRef Cohen, C., Revicki, D. A., Nabulsi, A., Sarocco, P. W., & Jiang, P. (1998). A randomized trial of the effect of ritonavir in maintaining quality of life in advanced HIV disease. Advanced HIV Disease Ritonavir Study Group. AIDS, 12(12), 1495–1502.PubMedCrossRef
4.
go back to reference Little, R. J. A., & Rubin, D. B. (1987). Statistical analysis with missing data. New York: John Wiley & Sons. Little, R. J. A., & Rubin, D. B. (1987). Statistical analysis with missing data. New York: John Wiley & Sons.
5.
go back to reference Donaldson, G. W., & Moinpour, C. M. (2005). Learning to live with missing quality-of-life data in advanced-stage disease trials. Journal of Clinical Oncology, 22(1), 1–5. Donaldson, G. W., & Moinpour, C. M. (2005). Learning to live with missing quality-of-life data in advanced-stage disease trials. Journal of Clinical Oncology, 22(1), 1–5.
6.
go back to reference Fairclough, D. L. et al. (1998). Comparison of several model-based methods for analysing incomplete quality of life data in cancer clinical trials. Statistics in Medicine, 17, 781–96.PubMedCrossRef Fairclough, D. L. et al. (1998). Comparison of several model-based methods for analysing incomplete quality of life data in cancer clinical trials. Statistics in Medicine, 17, 781–96.PubMedCrossRef
7.
go back to reference Fairclough, D. L. (2002). Design and analysis of quality of life studies in clinical trials. Boca Raton, Florida: Chapman & Hall/CRC. Fairclough, D. L. (2002). Design and analysis of quality of life studies in clinical trials. Boca Raton, Florida: Chapman & Hall/CRC.
8.
go back to reference Fairclough, D. L. (2004). Patient reported outcomes as endpoints in medical research. Statistical Methods in Medical Research, 13, 115–138.PubMedCrossRef Fairclough, D. L. (2004). Patient reported outcomes as endpoints in medical research. Statistical Methods in Medical Research, 13, 115–138.PubMedCrossRef
9.
go back to reference FDA. (2006). Draft guidance for industry on patient-reported outcome measures: use in medicinal product development to support labeling claims. Federal Register, 71, 5862–5863. FDA. (2006). Draft guidance for industry on patient-reported outcome measures: use in medicinal product development to support labeling claims. Federal Register, 71, 5862–5863.
10.
go back to reference Mallinckrodt, C. H., Christopher, J. Kaiser, C. J., Watkin, J. G., Detke, M. J., Molenberghs, G., & Carroll, R. J. (2004). Type I error rates from likelihood-based repeated measures analyses of incomplete longitudinal data. Pharmaceutical Statistics, 3, 171–186. Mallinckrodt, C. H., Christopher, J. Kaiser, C. J., Watkin, J. G., Detke, M. J., Molenberghs, G., & Carroll, R. J. (2004). Type I error rates from likelihood-based repeated measures analyses of incomplete longitudinal data. Pharmaceutical Statistics, 3, 171–186.
11.
go back to reference Schafer, J. L., & Graham, J. W. (2002). Missing data: our view of the state of the art. Psychological Methods, 7(2), 147–177.PubMedCrossRef Schafer, J. L., & Graham, J. W. (2002). Missing data: our view of the state of the art. Psychological Methods, 7(2), 147–177.PubMedCrossRef
12.
go back to reference Cohen, C. J., Clumeck, N., Molina, J. M., Thompson, M., Patel, K., Wintfeld, N., & Green, J. (2004). Health-related quality of life with enfuvirtide (ENF; T-20) in combination with an optimized background regimen. Journal of Acquired Immune Deficiency Syndromes, 37(1), 1140–1146.PubMedCrossRef Cohen, C. J., Clumeck, N., Molina, J. M., Thompson, M., Patel, K., Wintfeld, N., & Green, J. (2004). Health-related quality of life with enfuvirtide (ENF; T-20) in combination with an optimized background regimen. Journal of Acquired Immune Deficiency Syndromes, 37(1), 1140–1146.PubMedCrossRef
13.
go back to reference Revicki, D. A., Swartz, C., Wu, A. W., Haubrich, R., & Collier, A. C. (1999). Quality of life outcomes of saquinavir, zalcitabine and combination saquinavir plus zalcitabine therapy for adults with advanced HIV infection with CD4 counts between 50 and 300 cells/mm3. Antiviral Therapy, 4(1), 35–44.PubMed Revicki, D. A., Swartz, C., Wu, A. W., Haubrich, R., & Collier, A. C. (1999). Quality of life outcomes of saquinavir, zalcitabine and combination saquinavir plus zalcitabine therapy for adults with advanced HIV infection with CD4 counts between 50 and 300 cells/mm3. Antiviral Therapy, 4(1), 35–44.PubMed
14.
go back to reference van Leth, F., Conway, B., Laplume, H., Martin, D., Fisher, M., Jelaska, A., Wit, F. W., Lange, J. M. & 2NN study group. (2004). Quality of life in patients treated with first-line antiretroviral therapy containing nevirapine and/or efavirenz. Antiviral Therapy, 9(5), 721–728. van Leth, F., Conway, B., Laplume, H., Martin, D., Fisher, M., Jelaska, A., Wit, F. W., Lange, J. M. & 2NN study group. (2004). Quality of life in patients treated with first-line antiretroviral therapy containing nevirapine and/or efavirenz. Antiviral Therapy, 9(5), 721–728.
15.
go back to reference Casado, A., Badia, X., Consiglio, E., Ferrer, E., Gonzalez, A., Pedrol, E., Gatell, J. M., Azuaje, C., Llibre, J. M., Aranda, M., Barrufet, P., Martinez-Lacasa, J., Podzamczer, D., & COMBINE Study Team. (2004). Health-related quality of life in HIV-infected naive patients treated with nelfinavir or nevirapine associated with ZDV/3TC (the COMBINE-QoL substudy). HIV Clinical Trials, 5(3), 132–139. Casado, A., Badia, X., Consiglio, E., Ferrer, E., Gonzalez, A., Pedrol, E., Gatell, J. M., Azuaje, C., Llibre, J. M., Aranda, M., Barrufet, P., Martinez-Lacasa, J., Podzamczer, D., & COMBINE Study Team. (2004). Health-related quality of life in HIV-infected naive patients treated with nelfinavir or nevirapine associated with ZDV/3TC (the COMBINE-QoL substudy). HIV Clinical Trials, 5(3), 132–139.
16.
go back to reference Badia, X., Podzamczer, D., Moral, I., Roset, M., Arnaiz, J. A., Lonca, M., Casiro, A., Roson, B., Gatell, J. M., & BestQol Study Group. (2004). Health-related quality of life in HIV patients switching to twice-daily indinavir/ritonavir regimen or continuing with three-times-daily indinavir-based therapy. Antiviral Therapy, 9(6), 979–985. Badia, X., Podzamczer, D., Moral, I., Roset, M., Arnaiz, J. A., Lonca, M., Casiro, A., Roson, B., Gatell, J. M., & BestQol Study Group. (2004). Health-related quality of life in HIV patients switching to twice-daily indinavir/ritonavir regimen or continuing with three-times-daily indinavir-based therapy. Antiviral Therapy, 9(6), 979–985.
17.
go back to reference Hicks, C. B., Cahn, P., Cooper, D. A. et al. (2006). Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the randomized evaluation of strategic intervention in multi-drug reSistant patients with tipranavir (RESIST) studies: An analysis of combined data from two randomised open-label trials. Lancet, 36, 466–475.CrossRef Hicks, C. B., Cahn, P., Cooper, D. A. et al. (2006). Durable efficacy of tipranavir-ritonavir in combination with an optimised background regimen of antiretroviral drugs for treatment-experienced HIV-1-infected patients at 48 weeks in the randomized evaluation of strategic intervention in multi-drug reSistant patients with tipranavir (RESIST) studies: An analysis of combined data from two randomised open-label trials. Lancet, 36, 466–475.CrossRef
18.
go back to reference Revicki, D. A., Sorensen, S., & Wu, A. W. (1998). Reliability and validity of physical and mental health summary scores from the Medical Outcomes Study HIV Health Survey. Medical Care, 38, 126–137.CrossRef Revicki, D. A., Sorensen, S., & Wu, A. W. (1998). Reliability and validity of physical and mental health summary scores from the Medical Outcomes Study HIV Health Survey. Medical Care, 38, 126–137.CrossRef
19.
go back to reference Wu, A. W., Revicki, D. A., Jacobson, D., & Malitz, F. E. (1997). Evidence for reliability, validity and usefulness of the Medical Outcomes Study HIV Health Survey (MOS-HIV). Quality of Life Research, 6, 481–493.PubMedCrossRef Wu, A. W., Revicki, D. A., Jacobson, D., & Malitz, F. E. (1997). Evidence for reliability, validity and usefulness of the Medical Outcomes Study HIV Health Survey (MOS-HIV). Quality of Life Research, 6, 481–493.PubMedCrossRef
20.
go back to reference Heyting, A., Tolboom, J., & Essers, J. (1992). Statistical handling of dropouts in longitudinal clinical trials. Statistics in Medicine, 11, 2043–2061.PubMedCrossRef Heyting, A., Tolboom, J., & Essers, J. (1992). Statistical handling of dropouts in longitudinal clinical trials. Statistics in Medicine, 11, 2043–2061.PubMedCrossRef
21.
go back to reference Lavori, P. W., Dawson, R., & Shera, D. (1995). A multiple imputation strategy for clinical trials with truncation of patient data. Statistics in Medicine, 14, 1913–1925.PubMedCrossRef Lavori, P. W., Dawson, R., & Shera, D. (1995). A multiple imputation strategy for clinical trials with truncation of patient data. Statistics in Medicine, 14, 1913–1925.PubMedCrossRef
22.
go back to reference Mallinckrodt, C. H., Clairk, W. S., Carroll, R. J., & Molenberghs, G. (2003a). Assessing response profiles from incomplete longitudinal clinical trial data under regulatory considerations. Journal of Biopharmaceutical Statistics, 13, 179–190.PubMedCrossRef Mallinckrodt, C. H., Clairk, W. S., Carroll, R. J., & Molenberghs, G. (2003a). Assessing response profiles from incomplete longitudinal clinical trial data under regulatory considerations. Journal of Biopharmaceutical Statistics, 13, 179–190.PubMedCrossRef
23.
go back to reference Mallinckrodt, C. H., Sanger, T. M., Dube, S., Debrota, D. J., Molenberghs, G., Carroll, R. J., Zeigler Potter, W. M., & Tollefson, G. D. (2003b). Assessing and interpreting treatment effects in longitudinal clinical trials with missing data. Biological Psychiatry, 53, 754–760.PubMedCrossRef Mallinckrodt, C. H., Sanger, T. M., Dube, S., Debrota, D. J., Molenberghs, G., Carroll, R. J., Zeigler Potter, W. M., & Tollefson, G. D. (2003b). Assessing and interpreting treatment effects in longitudinal clinical trials with missing data. Biological Psychiatry, 53, 754–760.PubMedCrossRef
24.
go back to reference Siddiqui, O., & Ali, M. W. (1998). A comparison of the random-effects pattern mixture model with last observation carried forward (LOCF) analysis in longitudinal clinical trials with dropouts, Journal of Biopharmaceutical Statistics, 8, 545–563.PubMedCrossRef Siddiqui, O., & Ali, M. W. (1998). A comparison of the random-effects pattern mixture model with last observation carried forward (LOCF) analysis in longitudinal clinical trials with dropouts, Journal of Biopharmaceutical Statistics, 8, 545–563.PubMedCrossRef
25.
go back to reference Laird, N. M., & Ware, J. H. (1982). Random effects models for longitudinal data. Biometrics, 38, 963–974.PubMedCrossRef Laird, N. M., & Ware, J. H. (1982). Random effects models for longitudinal data. Biometrics, 38, 963–974.PubMedCrossRef
26.
go back to reference Schluchter, M. D. (1992). Methods for the analysis of informatively censored longitudinal data. Statistics in Medicine, 11, 1861–1870.PubMedCrossRef Schluchter, M. D. (1992). Methods for the analysis of informatively censored longitudinal data. Statistics in Medicine, 11, 1861–1870.PubMedCrossRef
27.
go back to reference DeGruttola, V., & Tu, X. M. (1994). Modeling progression of CD4-lymphocyte count and its relationship to survival time. Biometrics, 50(4), 1003–1014.CrossRef DeGruttola, V., & Tu, X. M. (1994). Modeling progression of CD4-lymphocyte count and its relationship to survival time. Biometrics, 50(4), 1003–1014.CrossRef
28.
go back to reference Rubin, D. B. (1976). Inference and missing data. Biometrika, 63, 581–592.CrossRef Rubin, D. B. (1976). Inference and missing data. Biometrika, 63, 581–592.CrossRef
29.
go back to reference Rubin, D. B., & Schenker, N. (1986). Multiple imputation for interval estimation from simple random samples with ignorable nonresponse. Journal of the American Statistical Association, 81, 366–374.CrossRef Rubin, D. B., & Schenker, N. (1986). Multiple imputation for interval estimation from simple random samples with ignorable nonresponse. Journal of the American Statistical Association, 81, 366–374.CrossRef
30.
go back to reference Schafer, J. L. (1997). Analysis of incomplete multivariate data. Chapman and Hall, London. Schafer, J. L. (1997). Analysis of incomplete multivariate data. Chapman and Hall, London.
31.
go back to reference Tanner, M. A., & Wong, W. H. (1987). The calculation of posterior distributions by data augmentation (with discussion). Journal of the American Statistical Association, 82, 528–550.CrossRef Tanner, M. A., & Wong, W. H. (1987). The calculation of posterior distributions by data augmentation (with discussion). Journal of the American Statistical Association, 82, 528–550.CrossRef
32.
go back to reference Thijs, H., Molenberghs, G., Michiels, B., Verbeke, G., & Curran, D. (2002). Strategies to fit pattern-mixture models, Biostatistics, 3, 245–265.PubMedCrossRef Thijs, H., Molenberghs, G., Michiels, B., Verbeke, G., & Curran, D. (2002). Strategies to fit pattern-mixture models, Biostatistics, 3, 245–265.PubMedCrossRef
33.
go back to reference Dempster, A. P., & Rubin, D. B. (1983). Overview. In W. G. Madow, I. Olkin, & D. B. Rubin (Eds.), Incomplete data in sample surveys (Vol. II). Theory and annotated bibliography. New York: Academic Press (pp. 3–10). Dempster, A. P., & Rubin, D. B. (1983). Overview. In W. G. Madow, I. Olkin, & D. B. Rubin (Eds.), Incomplete data in sample surveys (Vol. II). Theory and annotated bibliography. New York: Academic Press (pp. 3–10).
34.
go back to reference Vonesh, E. F., Green, T., & Schluchter, M. D. (2006) Shared parameter models for the joint analysis of longitudinal data and event times. Statistics in Medicine, 25, 143–163.PubMedCrossRef Vonesh, E. F., Green, T., & Schluchter, M. D. (2006) Shared parameter models for the joint analysis of longitudinal data and event times. Statistics in Medicine, 25, 143–163.PubMedCrossRef
35.
go back to reference Guo, X., Carlin, B. P. (2004). Separate and joint modeling of longitudinal and event time data using standard computer packages. The American Statistician, 58, 16–24.CrossRef Guo, X., Carlin, B. P. (2004). Separate and joint modeling of longitudinal and event time data using standard computer packages. The American Statistician, 58, 16–24.CrossRef
Metagegevens
Titel
Handling missing quality of life data in HIV clinical trials: what is practical?
Auteurs
Diane L. Fairclough
Herbert Thijs
I-Chan Huang
Henrik W. Finnern
Albert W. Wu
Publicatiedatum
01-02-2008
Uitgeverij
Springer Netherlands
Gepubliceerd in
Quality of Life Research / Uitgave 1/2008
Print ISSN: 0962-9343
Elektronisch ISSN: 1573-2649
DOI
https://doi.org/10.1007/s11136-007-9284-3

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