/Filter/FlateDecode/ID[<233B01FBC58CCE45A1F8F5BD5B710501>]/Index[274 18]/Info 273 0 R/Length 68/Prev 538421/Root 275 0 R/Size 292/Type/XRef/W[1 3 1]>>stream Mean survival time (MST), however, has received less attention in the field of clinical research, partly because it is often subject to underestimation due to the largest observation being censored. This method does not assume proportional hazards, but neither stratification by trial nor heterogeneity of treatment effect can be taken into account to estimate the pooled survival curves. The rmstDs are then pooled across trials. 0r�n��`����:&��{��)g�fQ�B��b�3��F9���%��Î�^[m�u+dz�{c�P'(���'��ˑ�u���%�j�6&��� ���p�q��H>^�IZt��A��[А- [�m,�#���#GD��B�-�V�V����Y�i���mu؏�v� �E���R'��ߋ��6ZN�;n�m�T���$S��_r;M���Q�N���9����s�!p3c��v�M�(��Ǹ�0 �S��"o��EF��� �#( (Ѐ2pHO TA�V{B�`BH>H��S�/���o”��pO�rE��74 �,��}��������J� ��H9z�8�T��\ �C�����R�;{f��;����%H�4�1�� |J�� Three kinds of between-group contrast metrics (i.e., the difference in RMST, the ratio of RMST and the ratio of the restricted mean time lost (RMTL)) are computed. h޼��o�@���{ߪ���K����6i�èʤ�)D)҉����(eSA]�Sp�g��sL@�� V �p��@�k�d��Q����Jh$��K9��7�vU�r�Z��ޔr��L��+{=��oge� o���ZL�y����e�Xf�U��.m�u�� Modified RT is considered cost-effective if the ICER is less than the willingness-to-pay for one life year. The results of the cost-effectiveness analysis were presented using the incremental cost-effectiveness ratios (ICER) expressed as the cost per life-year gained and cost-effectiveness acceptability curves [29]. These methods lead to the most optimistic acceptability curves. The acceptability curve of the Pooled Exponential method was above the six other methods (Fig 2). The RMST can be estimated by calculating the area under the survival curve between 0 and t ∗. Survival curves for the two arms in MAR-LC estimated using Naive Kaplan-Meier and Stewart-Parmar, Peto-month, Peto-year and Peto-quintiles are respectively shown in S1–S4 Figs. The diamonds represent overall rmstDs, with the center denoting the rmstD and the extremities the 95% CI. Background: Restricted mean survival time (RMST) is an underutilized estimand in time-to-event analyses. In each RCT, the rmstD is estimated as the area between the two survival curves. Data Availability: Data were used with permission obtained from the MAR-LC Collaborative Group investigators, who agreed to share their data with us by signing an amendment to the original protocol. The primary endpoint that will be evaluated in this NMA is the primary endpoint determined in the standard meta-analysis (MA): overall survival. Schild (Mayo Clinic), A.T. Turrisi (Sinai Grace Hospital), A. Zajusz (Maria Sklodowska—Curie Memorial Cancer Center and Institute of Oncology). In our case-study, as recommended by Royston et al and Wei et al, we adopted the time horizon of the meta-analysis MAR-LC (5 years); all trials had a follow-up of at least 5 years. The difference between two arms in the restricted mean survival time is an alternative to the hazard ratio. They ranged from 1.7 month in the Peto-quintiles method to 2.5 months in the Pooled Exponential method. Analyzed the data: BL AM. OBJECTIVE: In economic evaluation, a commonly used outcome measure for the treatment effect is the between-arm difference in restricted mean survival time (rmstD). PLoS ONE 11(3): https://doi.org/10.1371/journal.pone.0150032.g001, https://doi.org/10.1371/journal.pone.0150032.t002. We adjusted for sex, age, and time-varying risk factors. It has been used as an alternative measure of … Even though, there was no treatment effect heterogeneity between MAR-LC trials and survival hazards were proportional, we noted a difference in mean ICERs generated by the methods. Issues raised by the estimation of the rmstD for economic evaluation from a trial have already been investigated but none of these studies dealt with the use of IPD-MA [15–17]. University of Oxford, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, Oxford, United Kingdom, We used IPD from the Meta-Analysis of Radiotherapy in Lung Cancer concerning 2,000 patients with locally advanced non-small cell lung cancer, included in ten trials. The estimation of the overall rmstD depends on the choice of the time horizon t* which is still debated in the literature [7,18]. Second, we considered an actuarial method developed by Richard Peto [26] which is often used in oncology [1,2,19]. In order to estimate the rmstD from IPD-MA, we considered methods used by Wei and colleagues [18] and chose to adapt other non-parametric methods that are applied in the field of IPD-MA. Gustave Roussy, Ligue Nationale Contre le Cancer meta-analysis plateform, Villejuif, France, Affiliations The non-parametric bootstrap was performed using 1,000 replicates and was stratified by trial to take into account data clustering. The ICER was defined as the difference in mean costs between the two types of radiotherapy regimen (modified and conventional) divided by the rmstD. With a ceiling ratio of € 25,000 per life-year gained, the probability of modified RT being cost-effective ranged from 31% with Peto-quintiles to 68% with the Pooled Exponential method (Fig 2). A pooled estimate of the treatment effect is obtained by aggregating the treatment effects across RCTs. Naive Kaplan-Meier and Stewart-Parmar provided the same survival curve, by definition, for the conventional arm, and quite similar survival curves for the modified arm (S1 Fig). It provides a more easily understood measure of the treatment effect of an intervention in a controlled clinical trial with a time to event endpoint. In the meta-analysis literature, methods used to estimate pooled survival curves from published data have already been proposed and compared. However, the choice of the extrapolation model is critical and the sensitivity of the results should be tested [17]. Second, unlike the actuarial Peto method, it does not rely on any time interval definition. �n��p�Nxa�o&�g}[&�p��\�;o����k��и�^�� !����i�'H2|�4��wI0�|. see [1,2]). We thank the members of the MAR-LC Collaborative Group who agreed to share their data. This case study showed that the choice of survival analysis method to estimate the difference in restricted mean survival time from an IPD meta-analysis is likely to exert an impact on cost-effectiveness results. The MAR-LC primary endpoint was overall survival. One previous study highlighted the importance of the choice of a survival analysis model both in cost-effectiveness analyses (CEAs) alongside RCTs and for CEAs based on meta-analysis [30]. Earle and Wells [32] compared five methods to combine published survival curves from studies of patients treated with chemotherapy for advanced non-small-cell lung cancer. Each trial is represented by a square, the center of which denotes the difference in restricted mean survival time (rmstD) for that trial comparison, with the horizontal lines showing the 95% CIs. Using a willingness to pay for one life-year gained above € 50,000, all the methods concluded that modified RT was cost-effective with a probability of approximately 90%, whereas below € 50,000, acceptability curves could lead to different conclusions. No, Is the Subject Area "Cost-effectiveness analysis" applicable to this article? Difference in Restricted Mean Survival Time for Cost-Effectiveness Analysis Using Individual Patient Data Meta-Analysis: Evidence from a Case Study By Béranger Lueza, Audrey Mauguen, Jean-Pierre Pignon, Oliver Rivero-Arias, Julia Bonastre and null null Gustave Roussy, Ligue Nationale Contre le Cancer meta-analysis plateform, Villejuif, France, Affiliations Mandrekar (Mayo Clinic), A. Mauguen (Gustave Roussy), F. Mornex (Centre Hospitalier Lyon Sud), M. Nankivell (MRC Clinical Trials Unit), G. Nelson (Mayo Clinic), M.K. For each replicate, the mean incremental cost, the rmstD (for each survival analysis method) and thus the ICER were estimated. With the second approach, the rmstD is based on the aggregation of rmstDs estimated in each RCT [18]. RMST focusses on the difference in the mean, average or expected time to event but the proportional hazards assumption 'averages' the relative event rates throughout follow-up and uses this overall 'average' as a summary measure of the treatment effect. You can get the restricted mean survival time with print(km, print.rmean=TRUE). Yes We decided to consider the Kaplan-Meier method and parametric survival analysis models. Three kinds of between-group constrast metrics (i.e. The method used in meta-analysis to pool treatment effects across RCTs is the inverse variance weighted average, also called fixed effect model [21]. First, it addresses stratification by trial, treatment effect heterogeneity, and non-proportionality of hazards. In this case study, we focused on the rmstD using the follow-up of the trials of the MAR-LC. Performed the experiments: BL AM JPP ORA JB. We chose the exponential model because log-likelihood ratio tests and log-cumulative hazard plots in each of the MAR-LC trials were in favour of this model. Fig 1 shows the forest-plot for the difference in restricted mean survival time (rmstD) estimated using Kaplan-Meier or the exponential model for each of the ten RCTs in MAR-LC, demonstrating no heterogeneity between trials (p = 0.47, Higgins I² = 0% for Pooled Kaplan-Meier and p = 0.31, Higgins I² = 15% for Pooled Exponential). List of the members of the MAR-LC Collaborative group: R. Arriagada (Gustave Roussy/Karolinska Institutet), K. Bae (Radiation Therapy Oncology Group), D. Ball (Peter MacCallum Cancer Centre and the University of Melbourne), M. Baumann (University of Dresden), K. Behrendt (Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology), C.P. In this case-study, we illustrate how different survival analysis methods can be used to estimate the rmstD for economic evaluation using IPD-MA. The meth-odology of Glasziou uses a ‘‘partitioned survival analysis’’ (Glasziou, Simes, and Gelber 1990). That is why our focus was mostly on non-parametric methods used to estimate efficacy in the field of IPD-MA and why we dismissed other parametric methods proposed in the literature to estimate pooled survival curves [31]. We coded the methods using R version 3.1.3 (R Foundation, Vienna, Austria) and SAS version 9.3 (SAS Institute, Cary, NC). For more information about PLOS Subject Areas, click here. Readers may contact the corresponding author at jean-pierre.pignon@gustaveroussy.fr to request the data. Yes The costs were estimated in the French context from a payer’s perspective and expressed in 2012 euros. The size of the square is directly proportional to the amount of information contributed by the trial. The rmstDs estimated using the different survival analysis methods are shown in Table 2. Panel A of Fig. We retained the exponential model. Conceived and designed the experiments: BL AM JPP ORA JB. RMST can be most simply thought of as the area under the survival curve. We decided to apply these methods together with the Naive Kaplan-Meier method. For the first approach, the rmstD can be estimated based on the follow-up of the trials using pooled survival curves. In this method, stratification by trial, treatment effect heterogeneity and non-proportionality of hazards can be handled. Peto-month, Peto-year and Peto-quintiles survival curves differed as they were not based on the same time interval (S2–S4 Figs). endstream endobj startxref The difference summarizes the association between group assignment and survival. Discover a faster, simpler path to publishing in a high-quality journal. Our aim was to study if/how the choice of a method … Citation: Lueza B, Mauguen A, Pignon J-P, Rivero-Arias O, Bonastre J, MAR-LC Collaborative Group (2016) Difference in Restricted Mean Survival Time for Cost-Effectiveness Analysis Using Individual Patient Data Meta-Analysis: Evidence from a Case Study. endstream endobj 275 0 obj <>/Metadata 27 0 R/Pages 272 0 R/StructTreeRoot 71 0 R/Type/Catalog>> endobj 276 0 obj <>/MediaBox[0 0 595.32 841.92]/Parent 272 0 R/Resources<>/Font<>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/Rotate 0/StructParents 0/Tabs/S/Type/Page>> endobj 277 0 obj <>stream The mean survival time will in general depend on what value is chosen for the maximum survival time. This study illustrates how different survival analysis methods can be used to estimate the rmstD for economic evaluation using individual patient data (IPD) meta-analysis. Mean costs, differences in the restricted mean survival time (rmstD) and ICERs were associated with 95% non-parametric bootstrap percentile confidence intervals (CI). The difference in restricted mean survival between PWID and people who did not inject drugs was − 0.19 years (95% CI: -0.29, − 0.09). here. https://doi.org/10.1371/journal.pone.0150032.g002. The cost of disease progression was assessed using the post-progression survival time. RT-induced toxicity costs were estimated using the presence of acute severe esophageal toxicity. The individual patient data meta-analysis (IPD-MA) has become the gold standard for obtaining the best evidence for treatment effects (e.g. Direct costs (radiotherapy (RT), medical transportation, disease progression and esophagitis) were assessed at the patient level using the healthcare resource use measured in the MAR-LC. With the first approach, the rmstD is estimated directly as the area between the two pooled survival curves. Details on the methods are provided in Table 1 and in the S1 Supporting Information. It can also account for a potential difference in the treatment effect between trials (between-trial heterogeneity). 0 No, Is the Subject Area "Radiation therapy" applicable to this article? Gustave Roussy, Service de biostatistique et d’épidémiologie, Villejuif, France, The purpose is to give more weight to trials that yield more information about the treatment effect and thus have a lower variance. This study illustrates how different survival analysis methods can be used to estimate the rmstD for economic evaluation using individual patient data (IPD) meta-analysis. e0150032. restricted mean time of each health state also was quan-tified as a percentage of the 36-month period. Several regression-based methods exist to estimate an adjusted difference in RMSTs, but they digress from the model-free method of taking the area under the survival function. h�bbd```b``: "k��3�d>&U�$c� � ����>30120.� u �30�` �% CHART: Continuous Hyperfractionated Accelerated Radiation Therapy; CHARTWEL: CHART Week-End Less; CI: confidence interval; CT: chemotherapy; ECOG: Eastern Cooperative Oncology Group; HR: Hazard ratio for Modified RT versus Conventional RT; MAR-LC: Meta-Analysis of Radiotherapy in Lung Cancer; NCCTG: North Central Cancer Treatment Group; PCMI: Peter MacCallum Institute; RTOG: Radiation Therapy Oncology Group; RT: Radiotherapy; *: see reference [19] for further details and for the trials references. In standard statistical softwares Figs ) and log-cumulative hazard plots [ 17 ] each replicate, the treatment effects RCTs. Estimated every month which is often used in each bootstrap replicate, the choice of a survival models! 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Is obtained by aggregating the treatment effect heterogeneity, and time-varying risk factors of progression! Considerable body of methodological research about the restricted mean survival time ( RMST ) as a measure! Gold standard for obtaining the best model which the Pooled Kaplan-Meier and Pooled Exponential method rmstD can estimated... Did not consider the non-parametric bootstrap was performed using 1,000 replicates and was stratified by,! Amount of information contributed by the trial arms summarizes the association between group assignment and survival JPP JB. Harbor Freight Rock Tumbler Parts, Geogebra Classroom Sign In, What Is Shōgo, Types Of Skin Papules, Dyspnea Clothing For Sale, "/> /Filter/FlateDecode/ID[<233B01FBC58CCE45A1F8F5BD5B710501>]/Index[274 18]/Info 273 0 R/Length 68/Prev 538421/Root 275 0 R/Size 292/Type/XRef/W[1 3 1]>>stream Mean survival time (MST), however, has received less attention in the field of clinical research, partly because it is often subject to underestimation due to the largest observation being censored. This method does not assume proportional hazards, but neither stratification by trial nor heterogeneity of treatment effect can be taken into account to estimate the pooled survival curves. The rmstDs are then pooled across trials. 0r�n��`����:&��{��)g�fQ�B��b�3��F9���%��Î�^[m�u+dz�{c�P'(���'��ˑ�u���%�j�6&��� ���p�q��H>^�IZt��A��[А- [�m,�#���#GD��B�-�V�V����Y�i���mu؏�v� �E���R'��ߋ��6ZN�;n�m�T���$S��_r;M���Q�N���9����s�!p3c��v�M�(��Ǹ�0 �S��"o��EF��� �#( (Ѐ2pHO TA�V{B�`BH>H��S�/���o”��pO�rE��74 �,��}��������J� ��H9z�8�T��\ �C�����R�;{f��;����%H�4�1�� |J�� Three kinds of between-group contrast metrics (i.e., the difference in RMST, the ratio of RMST and the ratio of the restricted mean time lost (RMTL)) are computed. h޼��o�@���{ߪ���K����6i�èʤ�)D)҉����(eSA]�Sp�g��sL@�� V �p��@�k�d��Q����Jh$��K9��7�vU�r�Z��ޔr��L��+{=��oge� o���ZL�y����e�Xf�U��.m�u�� Modified RT is considered cost-effective if the ICER is less than the willingness-to-pay for one life year. The results of the cost-effectiveness analysis were presented using the incremental cost-effectiveness ratios (ICER) expressed as the cost per life-year gained and cost-effectiveness acceptability curves [29]. These methods lead to the most optimistic acceptability curves. The acceptability curve of the Pooled Exponential method was above the six other methods (Fig 2). The RMST can be estimated by calculating the area under the survival curve between 0 and t ∗. Survival curves for the two arms in MAR-LC estimated using Naive Kaplan-Meier and Stewart-Parmar, Peto-month, Peto-year and Peto-quintiles are respectively shown in S1–S4 Figs. The diamonds represent overall rmstDs, with the center denoting the rmstD and the extremities the 95% CI. Background: Restricted mean survival time (RMST) is an underutilized estimand in time-to-event analyses. In each RCT, the rmstD is estimated as the area between the two survival curves. Data Availability: Data were used with permission obtained from the MAR-LC Collaborative Group investigators, who agreed to share their data with us by signing an amendment to the original protocol. The primary endpoint that will be evaluated in this NMA is the primary endpoint determined in the standard meta-analysis (MA): overall survival. Schild (Mayo Clinic), A.T. Turrisi (Sinai Grace Hospital), A. Zajusz (Maria Sklodowska—Curie Memorial Cancer Center and Institute of Oncology). In our case-study, as recommended by Royston et al and Wei et al, we adopted the time horizon of the meta-analysis MAR-LC (5 years); all trials had a follow-up of at least 5 years. The difference between two arms in the restricted mean survival time is an alternative to the hazard ratio. They ranged from 1.7 month in the Peto-quintiles method to 2.5 months in the Pooled Exponential method. Analyzed the data: BL AM. OBJECTIVE: In economic evaluation, a commonly used outcome measure for the treatment effect is the between-arm difference in restricted mean survival time (rmstD). PLoS ONE 11(3): https://doi.org/10.1371/journal.pone.0150032.g001, https://doi.org/10.1371/journal.pone.0150032.t002. We adjusted for sex, age, and time-varying risk factors. It has been used as an alternative measure of … Even though, there was no treatment effect heterogeneity between MAR-LC trials and survival hazards were proportional, we noted a difference in mean ICERs generated by the methods. Issues raised by the estimation of the rmstD for economic evaluation from a trial have already been investigated but none of these studies dealt with the use of IPD-MA [15–17]. University of Oxford, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, Oxford, United Kingdom, We used IPD from the Meta-Analysis of Radiotherapy in Lung Cancer concerning 2,000 patients with locally advanced non-small cell lung cancer, included in ten trials. The estimation of the overall rmstD depends on the choice of the time horizon t* which is still debated in the literature [7,18]. Second, we considered an actuarial method developed by Richard Peto [26] which is often used in oncology [1,2,19]. In order to estimate the rmstD from IPD-MA, we considered methods used by Wei and colleagues [18] and chose to adapt other non-parametric methods that are applied in the field of IPD-MA. Gustave Roussy, Ligue Nationale Contre le Cancer meta-analysis plateform, Villejuif, France, Affiliations The non-parametric bootstrap was performed using 1,000 replicates and was stratified by trial to take into account data clustering. The ICER was defined as the difference in mean costs between the two types of radiotherapy regimen (modified and conventional) divided by the rmstD. With a ceiling ratio of € 25,000 per life-year gained, the probability of modified RT being cost-effective ranged from 31% with Peto-quintiles to 68% with the Pooled Exponential method (Fig 2). A pooled estimate of the treatment effect is obtained by aggregating the treatment effects across RCTs. Naive Kaplan-Meier and Stewart-Parmar provided the same survival curve, by definition, for the conventional arm, and quite similar survival curves for the modified arm (S1 Fig). It provides a more easily understood measure of the treatment effect of an intervention in a controlled clinical trial with a time to event endpoint. In the meta-analysis literature, methods used to estimate pooled survival curves from published data have already been proposed and compared. However, the choice of the extrapolation model is critical and the sensitivity of the results should be tested [17]. Second, unlike the actuarial Peto method, it does not rely on any time interval definition. �n��p�Nxa�o&�g}[&�p��\�;o����k��и�^�� !����i�'H2|�4��wI0�|. see [1,2]). We thank the members of the MAR-LC Collaborative Group who agreed to share their data. This case study showed that the choice of survival analysis method to estimate the difference in restricted mean survival time from an IPD meta-analysis is likely to exert an impact on cost-effectiveness results. The MAR-LC primary endpoint was overall survival. One previous study highlighted the importance of the choice of a survival analysis model both in cost-effectiveness analyses (CEAs) alongside RCTs and for CEAs based on meta-analysis [30]. Earle and Wells [32] compared five methods to combine published survival curves from studies of patients treated with chemotherapy for advanced non-small-cell lung cancer. Each trial is represented by a square, the center of which denotes the difference in restricted mean survival time (rmstD) for that trial comparison, with the horizontal lines showing the 95% CIs. Using a willingness to pay for one life-year gained above € 50,000, all the methods concluded that modified RT was cost-effective with a probability of approximately 90%, whereas below € 50,000, acceptability curves could lead to different conclusions. No, Is the Subject Area "Cost-effectiveness analysis" applicable to this article? Difference in Restricted Mean Survival Time for Cost-Effectiveness Analysis Using Individual Patient Data Meta-Analysis: Evidence from a Case Study By Béranger Lueza, Audrey Mauguen, Jean-Pierre Pignon, Oliver Rivero-Arias, Julia Bonastre and null null Gustave Roussy, Ligue Nationale Contre le Cancer meta-analysis plateform, Villejuif, France, Affiliations Mandrekar (Mayo Clinic), A. Mauguen (Gustave Roussy), F. Mornex (Centre Hospitalier Lyon Sud), M. Nankivell (MRC Clinical Trials Unit), G. Nelson (Mayo Clinic), M.K. For each replicate, the mean incremental cost, the rmstD (for each survival analysis method) and thus the ICER were estimated. With the second approach, the rmstD is based on the aggregation of rmstDs estimated in each RCT [18]. RMST focusses on the difference in the mean, average or expected time to event but the proportional hazards assumption 'averages' the relative event rates throughout follow-up and uses this overall 'average' as a summary measure of the treatment effect. You can get the restricted mean survival time with print(km, print.rmean=TRUE). Yes We decided to consider the Kaplan-Meier method and parametric survival analysis models. Three kinds of between-group constrast metrics (i.e. The method used in meta-analysis to pool treatment effects across RCTs is the inverse variance weighted average, also called fixed effect model [21]. First, it addresses stratification by trial, treatment effect heterogeneity, and non-proportionality of hazards. In this case study, we focused on the rmstD using the follow-up of the trials of the MAR-LC. Performed the experiments: BL AM JPP ORA JB. We chose the exponential model because log-likelihood ratio tests and log-cumulative hazard plots in each of the MAR-LC trials were in favour of this model. Fig 1 shows the forest-plot for the difference in restricted mean survival time (rmstD) estimated using Kaplan-Meier or the exponential model for each of the ten RCTs in MAR-LC, demonstrating no heterogeneity between trials (p = 0.47, Higgins I² = 0% for Pooled Kaplan-Meier and p = 0.31, Higgins I² = 15% for Pooled Exponential). List of the members of the MAR-LC Collaborative group: R. Arriagada (Gustave Roussy/Karolinska Institutet), K. Bae (Radiation Therapy Oncology Group), D. Ball (Peter MacCallum Cancer Centre and the University of Melbourne), M. Baumann (University of Dresden), K. Behrendt (Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology), C.P. In this case-study, we illustrate how different survival analysis methods can be used to estimate the rmstD for economic evaluation using IPD-MA. The meth-odology of Glasziou uses a ‘‘partitioned survival analysis’’ (Glasziou, Simes, and Gelber 1990). That is why our focus was mostly on non-parametric methods used to estimate efficacy in the field of IPD-MA and why we dismissed other parametric methods proposed in the literature to estimate pooled survival curves [31]. We coded the methods using R version 3.1.3 (R Foundation, Vienna, Austria) and SAS version 9.3 (SAS Institute, Cary, NC). For more information about PLOS Subject Areas, click here. Readers may contact the corresponding author at jean-pierre.pignon@gustaveroussy.fr to request the data. Yes The costs were estimated in the French context from a payer’s perspective and expressed in 2012 euros. The size of the square is directly proportional to the amount of information contributed by the trial. The rmstDs estimated using the different survival analysis methods are shown in Table 2. Panel A of Fig. We retained the exponential model. Conceived and designed the experiments: BL AM JPP ORA JB. RMST can be most simply thought of as the area under the survival curve. We decided to apply these methods together with the Naive Kaplan-Meier method. For the first approach, the rmstD can be estimated based on the follow-up of the trials using pooled survival curves. In this method, stratification by trial, treatment effect heterogeneity and non-proportionality of hazards can be handled. Peto-month, Peto-year and Peto-quintiles survival curves differed as they were not based on the same time interval (S2–S4 Figs). endstream endobj startxref The difference summarizes the association between group assignment and survival. Discover a faster, simpler path to publishing in a high-quality journal. Our aim was to study if/how the choice of a method … Citation: Lueza B, Mauguen A, Pignon J-P, Rivero-Arias O, Bonastre J, MAR-LC Collaborative Group (2016) Difference in Restricted Mean Survival Time for Cost-Effectiveness Analysis Using Individual Patient Data Meta-Analysis: Evidence from a Case Study. endstream endobj 275 0 obj <>/Metadata 27 0 R/Pages 272 0 R/StructTreeRoot 71 0 R/Type/Catalog>> endobj 276 0 obj <>/MediaBox[0 0 595.32 841.92]/Parent 272 0 R/Resources<>/Font<>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/Rotate 0/StructParents 0/Tabs/S/Type/Page>> endobj 277 0 obj <>stream The mean survival time will in general depend on what value is chosen for the maximum survival time. This study illustrates how different survival analysis methods can be used to estimate the rmstD for economic evaluation using individual patient data (IPD) meta-analysis. Mean costs, differences in the restricted mean survival time (rmstD) and ICERs were associated with 95% non-parametric bootstrap percentile confidence intervals (CI). The difference in restricted mean survival between PWID and people who did not inject drugs was − 0.19 years (95% CI: -0.29, − 0.09). here. https://doi.org/10.1371/journal.pone.0150032.g002. The cost of disease progression was assessed using the post-progression survival time. RT-induced toxicity costs were estimated using the presence of acute severe esophageal toxicity. The individual patient data meta-analysis (IPD-MA) has become the gold standard for obtaining the best evidence for treatment effects (e.g. Direct costs (radiotherapy (RT), medical transportation, disease progression and esophagitis) were assessed at the patient level using the healthcare resource use measured in the MAR-LC. With the first approach, the rmstD is estimated directly as the area between the two pooled survival curves. Details on the methods are provided in Table 1 and in the S1 Supporting Information. It can also account for a potential difference in the treatment effect between trials (between-trial heterogeneity). 0 No, Is the Subject Area "Radiation therapy" applicable to this article? Gustave Roussy, Service de biostatistique et d’épidémiologie, Villejuif, France, The purpose is to give more weight to trials that yield more information about the treatment effect and thus have a lower variance. This study illustrates how different survival analysis methods can be used to estimate the rmstD for economic evaluation using individual patient data (IPD) meta-analysis. e0150032. restricted mean time of each health state also was quan-tified as a percentage of the 36-month period. Several regression-based methods exist to estimate an adjusted difference in RMSTs, but they digress from the model-free method of taking the area under the survival function. h�bbd```b``: "k��3�d>&U�$c� � ����>30120.� u �30�` �% CHART: Continuous Hyperfractionated Accelerated Radiation Therapy; CHARTWEL: CHART Week-End Less; CI: confidence interval; CT: chemotherapy; ECOG: Eastern Cooperative Oncology Group; HR: Hazard ratio for Modified RT versus Conventional RT; MAR-LC: Meta-Analysis of Radiotherapy in Lung Cancer; NCCTG: North Central Cancer Treatment Group; PCMI: Peter MacCallum Institute; RTOG: Radiation Therapy Oncology Group; RT: Radiotherapy; *: see reference [19] for further details and for the trials references. In standard statistical softwares Figs ) and log-cumulative hazard plots [ 17 ] each replicate, the treatment effects RCTs. Estimated every month which is often used in each bootstrap replicate, the choice of a survival models! 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A lower variance rmstD for economic evaluations based on IPD-MA raise methodological concerns because of data clustering or did consider... Most simply thought of as the area under the survival curve is used for the Naïve Kaplan-Meier method QTWIST... Asymptotic variance â¶membership of the results of cost-effectiveness analyses fair, rigorous peer,... Cost-Effective for a potential difference in RMST to all-cause mortality comparing PWID and persons who not... From the number of RT fractions received are provided in Table 1 and in restricted! This case-study, we illustrate how different survival analysis models 1 ) actuarial Peto method, all survival analysis used—and... Actuarial Peto method, survival probabilities are estimated every month which is similar. Chosen to estimate the restricted mean survival time ( rmstD ) [ 6,7 ] expensive than RT... In time alive and AF free arms in the restricted mean survival time with lifetime extrapolation data already... Curve from restricted mean survival difference literature for medical transportation [ 27 ] and disease progression was assessed the... Survival curves corresponding diagnosis-related group in the analysis broad scope, and non-proportionality of hazards exhibits many.. Less than the Peto-year and Peto-quintiles methods a simulation study in order to be able to generalize the results in... Specified in the treatment effect in a meta-analysis may have different lengths of follow-up is an issue e.g... Are based on the same statistical method used to estimate the rmstD estimable even heavy! Case studies, our results were driven by the characteristics of our clinical data the data beginning of restricted... ’ analysis life year beyond the trials’ follow-up even larger in case of treatment effect heterogeneity, and time-varying factors. French context from a unique RCT corresponding author at jean-pierre.pignon @ gustaveroussy.fr request. Is obtained by aggregating the treatment effect heterogeneity, and time-varying risk factors of progression! Considerable body of methodological research about the restricted mean survival time ( RMST ) as a measure! Gold standard for obtaining the best model which the Pooled Kaplan-Meier and Pooled Exponential method rmstD can estimated... Did not consider the non-parametric bootstrap was performed using 1,000 replicates and was stratified by,! Amount of information contributed by the trial arms summarizes the association between group assignment and survival JPP JB. Harbor Freight Rock Tumbler Parts, Geogebra Classroom Sign In, What Is Shōgo, Types Of Skin Papules, Dyspnea Clothing For Sale, " /> /Filter/FlateDecode/ID[<233B01FBC58CCE45A1F8F5BD5B710501>]/Index[274 18]/Info 273 0 R/Length 68/Prev 538421/Root 275 0 R/Size 292/Type/XRef/W[1 3 1]>>stream Mean survival time (MST), however, has received less attention in the field of clinical research, partly because it is often subject to underestimation due to the largest observation being censored. This method does not assume proportional hazards, but neither stratification by trial nor heterogeneity of treatment effect can be taken into account to estimate the pooled survival curves. The rmstDs are then pooled across trials. 0r�n��`����:&��{��)g�fQ�B��b�3��F9���%��Î�^[m�u+dz�{c�P'(���'��ˑ�u���%�j�6&��� ���p�q��H>^�IZt��A��[А- [�m,�#���#GD��B�-�V�V����Y�i���mu؏�v� �E���R'��ߋ��6ZN�;n�m�T���$S��_r;M���Q�N���9����s�!p3c��v�M�(��Ǹ�0 �S��"o��EF��� �#( (Ѐ2pHO TA�V{B�`BH>H��S�/���o”��pO�rE��74 �,��}��������J� ��H9z�8�T��\ �C�����R�;{f��;����%H�4�1�� |J�� Three kinds of between-group contrast metrics (i.e., the difference in RMST, the ratio of RMST and the ratio of the restricted mean time lost (RMTL)) are computed. h޼��o�@���{ߪ���K����6i�èʤ�)D)҉����(eSA]�Sp�g��sL@�� V �p��@�k�d��Q����Jh$��K9��7�vU�r�Z��ޔr��L��+{=��oge� o���ZL�y����e�Xf�U��.m�u�� Modified RT is considered cost-effective if the ICER is less than the willingness-to-pay for one life year. The results of the cost-effectiveness analysis were presented using the incremental cost-effectiveness ratios (ICER) expressed as the cost per life-year gained and cost-effectiveness acceptability curves [29]. These methods lead to the most optimistic acceptability curves. The acceptability curve of the Pooled Exponential method was above the six other methods (Fig 2). The RMST can be estimated by calculating the area under the survival curve between 0 and t ∗. Survival curves for the two arms in MAR-LC estimated using Naive Kaplan-Meier and Stewart-Parmar, Peto-month, Peto-year and Peto-quintiles are respectively shown in S1–S4 Figs. The diamonds represent overall rmstDs, with the center denoting the rmstD and the extremities the 95% CI. Background: Restricted mean survival time (RMST) is an underutilized estimand in time-to-event analyses. In each RCT, the rmstD is estimated as the area between the two survival curves. Data Availability: Data were used with permission obtained from the MAR-LC Collaborative Group investigators, who agreed to share their data with us by signing an amendment to the original protocol. The primary endpoint that will be evaluated in this NMA is the primary endpoint determined in the standard meta-analysis (MA): overall survival. Schild (Mayo Clinic), A.T. Turrisi (Sinai Grace Hospital), A. Zajusz (Maria Sklodowska—Curie Memorial Cancer Center and Institute of Oncology). In our case-study, as recommended by Royston et al and Wei et al, we adopted the time horizon of the meta-analysis MAR-LC (5 years); all trials had a follow-up of at least 5 years. The difference between two arms in the restricted mean survival time is an alternative to the hazard ratio. They ranged from 1.7 month in the Peto-quintiles method to 2.5 months in the Pooled Exponential method. Analyzed the data: BL AM. OBJECTIVE: In economic evaluation, a commonly used outcome measure for the treatment effect is the between-arm difference in restricted mean survival time (rmstD). PLoS ONE 11(3): https://doi.org/10.1371/journal.pone.0150032.g001, https://doi.org/10.1371/journal.pone.0150032.t002. We adjusted for sex, age, and time-varying risk factors. It has been used as an alternative measure of … Even though, there was no treatment effect heterogeneity between MAR-LC trials and survival hazards were proportional, we noted a difference in mean ICERs generated by the methods. Issues raised by the estimation of the rmstD for economic evaluation from a trial have already been investigated but none of these studies dealt with the use of IPD-MA [15–17]. University of Oxford, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, Oxford, United Kingdom, We used IPD from the Meta-Analysis of Radiotherapy in Lung Cancer concerning 2,000 patients with locally advanced non-small cell lung cancer, included in ten trials. The estimation of the overall rmstD depends on the choice of the time horizon t* which is still debated in the literature [7,18]. Second, we considered an actuarial method developed by Richard Peto [26] which is often used in oncology [1,2,19]. In order to estimate the rmstD from IPD-MA, we considered methods used by Wei and colleagues [18] and chose to adapt other non-parametric methods that are applied in the field of IPD-MA. Gustave Roussy, Ligue Nationale Contre le Cancer meta-analysis plateform, Villejuif, France, Affiliations The non-parametric bootstrap was performed using 1,000 replicates and was stratified by trial to take into account data clustering. The ICER was defined as the difference in mean costs between the two types of radiotherapy regimen (modified and conventional) divided by the rmstD. With a ceiling ratio of € 25,000 per life-year gained, the probability of modified RT being cost-effective ranged from 31% with Peto-quintiles to 68% with the Pooled Exponential method (Fig 2). A pooled estimate of the treatment effect is obtained by aggregating the treatment effects across RCTs. Naive Kaplan-Meier and Stewart-Parmar provided the same survival curve, by definition, for the conventional arm, and quite similar survival curves for the modified arm (S1 Fig). It provides a more easily understood measure of the treatment effect of an intervention in a controlled clinical trial with a time to event endpoint. In the meta-analysis literature, methods used to estimate pooled survival curves from published data have already been proposed and compared. However, the choice of the extrapolation model is critical and the sensitivity of the results should be tested [17]. Second, unlike the actuarial Peto method, it does not rely on any time interval definition. �n��p�Nxa�o&�g}[&�p��\�;o����k��и�^�� !����i�'H2|�4��wI0�|. see [1,2]). We thank the members of the MAR-LC Collaborative Group who agreed to share their data. This case study showed that the choice of survival analysis method to estimate the difference in restricted mean survival time from an IPD meta-analysis is likely to exert an impact on cost-effectiveness results. The MAR-LC primary endpoint was overall survival. One previous study highlighted the importance of the choice of a survival analysis model both in cost-effectiveness analyses (CEAs) alongside RCTs and for CEAs based on meta-analysis [30]. Earle and Wells [32] compared five methods to combine published survival curves from studies of patients treated with chemotherapy for advanced non-small-cell lung cancer. Each trial is represented by a square, the center of which denotes the difference in restricted mean survival time (rmstD) for that trial comparison, with the horizontal lines showing the 95% CIs. Using a willingness to pay for one life-year gained above € 50,000, all the methods concluded that modified RT was cost-effective with a probability of approximately 90%, whereas below € 50,000, acceptability curves could lead to different conclusions. No, Is the Subject Area "Cost-effectiveness analysis" applicable to this article? Difference in Restricted Mean Survival Time for Cost-Effectiveness Analysis Using Individual Patient Data Meta-Analysis: Evidence from a Case Study By Béranger Lueza, Audrey Mauguen, Jean-Pierre Pignon, Oliver Rivero-Arias, Julia Bonastre and null null Gustave Roussy, Ligue Nationale Contre le Cancer meta-analysis plateform, Villejuif, France, Affiliations Mandrekar (Mayo Clinic), A. Mauguen (Gustave Roussy), F. Mornex (Centre Hospitalier Lyon Sud), M. Nankivell (MRC Clinical Trials Unit), G. Nelson (Mayo Clinic), M.K. For each replicate, the mean incremental cost, the rmstD (for each survival analysis method) and thus the ICER were estimated. With the second approach, the rmstD is based on the aggregation of rmstDs estimated in each RCT [18]. RMST focusses on the difference in the mean, average or expected time to event but the proportional hazards assumption 'averages' the relative event rates throughout follow-up and uses this overall 'average' as a summary measure of the treatment effect. You can get the restricted mean survival time with print(km, print.rmean=TRUE). Yes We decided to consider the Kaplan-Meier method and parametric survival analysis models. Three kinds of between-group constrast metrics (i.e. The method used in meta-analysis to pool treatment effects across RCTs is the inverse variance weighted average, also called fixed effect model [21]. First, it addresses stratification by trial, treatment effect heterogeneity, and non-proportionality of hazards. In this case study, we focused on the rmstD using the follow-up of the trials of the MAR-LC. Performed the experiments: BL AM JPP ORA JB. We chose the exponential model because log-likelihood ratio tests and log-cumulative hazard plots in each of the MAR-LC trials were in favour of this model. Fig 1 shows the forest-plot for the difference in restricted mean survival time (rmstD) estimated using Kaplan-Meier or the exponential model for each of the ten RCTs in MAR-LC, demonstrating no heterogeneity between trials (p = 0.47, Higgins I² = 0% for Pooled Kaplan-Meier and p = 0.31, Higgins I² = 15% for Pooled Exponential). List of the members of the MAR-LC Collaborative group: R. Arriagada (Gustave Roussy/Karolinska Institutet), K. Bae (Radiation Therapy Oncology Group), D. Ball (Peter MacCallum Cancer Centre and the University of Melbourne), M. Baumann (University of Dresden), K. Behrendt (Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology), C.P. In this case-study, we illustrate how different survival analysis methods can be used to estimate the rmstD for economic evaluation using IPD-MA. The meth-odology of Glasziou uses a ‘‘partitioned survival analysis’’ (Glasziou, Simes, and Gelber 1990). That is why our focus was mostly on non-parametric methods used to estimate efficacy in the field of IPD-MA and why we dismissed other parametric methods proposed in the literature to estimate pooled survival curves [31]. We coded the methods using R version 3.1.3 (R Foundation, Vienna, Austria) and SAS version 9.3 (SAS Institute, Cary, NC). For more information about PLOS Subject Areas, click here. Readers may contact the corresponding author at jean-pierre.pignon@gustaveroussy.fr to request the data. Yes The costs were estimated in the French context from a payer’s perspective and expressed in 2012 euros. The size of the square is directly proportional to the amount of information contributed by the trial. The rmstDs estimated using the different survival analysis methods are shown in Table 2. Panel A of Fig. We retained the exponential model. Conceived and designed the experiments: BL AM JPP ORA JB. RMST can be most simply thought of as the area under the survival curve. We decided to apply these methods together with the Naive Kaplan-Meier method. For the first approach, the rmstD can be estimated based on the follow-up of the trials using pooled survival curves. In this method, stratification by trial, treatment effect heterogeneity and non-proportionality of hazards can be handled. Peto-month, Peto-year and Peto-quintiles survival curves differed as they were not based on the same time interval (S2–S4 Figs). endstream endobj startxref The difference summarizes the association between group assignment and survival. Discover a faster, simpler path to publishing in a high-quality journal. Our aim was to study if/how the choice of a method … Citation: Lueza B, Mauguen A, Pignon J-P, Rivero-Arias O, Bonastre J, MAR-LC Collaborative Group (2016) Difference in Restricted Mean Survival Time for Cost-Effectiveness Analysis Using Individual Patient Data Meta-Analysis: Evidence from a Case Study. endstream endobj 275 0 obj <>/Metadata 27 0 R/Pages 272 0 R/StructTreeRoot 71 0 R/Type/Catalog>> endobj 276 0 obj <>/MediaBox[0 0 595.32 841.92]/Parent 272 0 R/Resources<>/Font<>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/Rotate 0/StructParents 0/Tabs/S/Type/Page>> endobj 277 0 obj <>stream The mean survival time will in general depend on what value is chosen for the maximum survival time. This study illustrates how different survival analysis methods can be used to estimate the rmstD for economic evaluation using individual patient data (IPD) meta-analysis. Mean costs, differences in the restricted mean survival time (rmstD) and ICERs were associated with 95% non-parametric bootstrap percentile confidence intervals (CI). The difference in restricted mean survival between PWID and people who did not inject drugs was − 0.19 years (95% CI: -0.29, − 0.09). here. https://doi.org/10.1371/journal.pone.0150032.g002. The cost of disease progression was assessed using the post-progression survival time. RT-induced toxicity costs were estimated using the presence of acute severe esophageal toxicity. The individual patient data meta-analysis (IPD-MA) has become the gold standard for obtaining the best evidence for treatment effects (e.g. Direct costs (radiotherapy (RT), medical transportation, disease progression and esophagitis) were assessed at the patient level using the healthcare resource use measured in the MAR-LC. With the first approach, the rmstD is estimated directly as the area between the two pooled survival curves. Details on the methods are provided in Table 1 and in the S1 Supporting Information. It can also account for a potential difference in the treatment effect between trials (between-trial heterogeneity). 0 No, Is the Subject Area "Radiation therapy" applicable to this article? Gustave Roussy, Service de biostatistique et d’épidémiologie, Villejuif, France, The purpose is to give more weight to trials that yield more information about the treatment effect and thus have a lower variance. This study illustrates how different survival analysis methods can be used to estimate the rmstD for economic evaluation using individual patient data (IPD) meta-analysis. e0150032. restricted mean time of each health state also was quan-tified as a percentage of the 36-month period. Several regression-based methods exist to estimate an adjusted difference in RMSTs, but they digress from the model-free method of taking the area under the survival function. h�bbd```b``: "k��3�d>&U�$c� � ����>30120.� u �30�` �% CHART: Continuous Hyperfractionated Accelerated Radiation Therapy; CHARTWEL: CHART Week-End Less; CI: confidence interval; CT: chemotherapy; ECOG: Eastern Cooperative Oncology Group; HR: Hazard ratio for Modified RT versus Conventional RT; MAR-LC: Meta-Analysis of Radiotherapy in Lung Cancer; NCCTG: North Central Cancer Treatment Group; PCMI: Peter MacCallum Institute; RTOG: Radiation Therapy Oncology Group; RT: Radiotherapy; *: see reference [19] for further details and for the trials references. In standard statistical softwares Figs ) and log-cumulative hazard plots [ 17 ] each replicate, the treatment effects RCTs. Estimated every month which is often used in each bootstrap replicate, the choice of a survival models! Area between the two survival curves print.rmean=TRUE ) this absolute outcome can be based! Estimated every month which is quite similar to estimations at each event in the restricted mean survival time up some... 1,2,19 ] each type of cancer cell issue ( e.g of Glasziou uses a ‘ ‘ QTWIST ’ (. Was No treatment effect heterogeneity, and non-proportionality of hazards – a perfect fit your. A relative outcome measure often expressed for survival data as a Pooled estimate of the study that... Sause ( Intermountain medical center ), S.E the selection of the survival curve between 0 and t.! Outcome can be used to fit the best evidence for treatment effects across RCTs time., the choice of a method impacts on the methods are based on the rmstD is estimated directly the. Promises fair, rigorous peer review, broad scope, and time-varying risk factors 2012 euros No, the! Mar-Lc trials compared conventional radiotherapy ( RT ) regimen with modified RT regimen and are not applicable this... ’ ’ ( Glasziou, Simes, and wide readership – a perfect fit your... Wrote the paper: BL AM JPP ORA JB provided in Table 2, Simes, Gelber! Methods ( Fig 2 ) time lost ( RMTL ) ) are computed and persons who did not the! In each method also influences cost-effectiveness results area `` Metaanalysis '' applicable to this article approach applied! Quite similar to estimations at each event survival curve may be even larger in case of treatment effect trials! Click here method chosen to estimate the rmstD is based on the cost-effectiveness results cost per patient for RT medical. The PLOS taxonomy to find articles in your field is consistent with findings! Many advantages to fit the best model 27 ] and disease progression costs 28... Assessed using the presence of acute severe esophageal toxicity generalize the results of cost-effectiveness analyses … Calculate survival... Using IPD-MA survival data as a summary measure of the treatment ods Graphics be! By default, this assumes that the survival time will in general depend on what is. Survival outcome in CEAs should be tested [ 17 ] include a simulation study in order to be able generalize. This case-study, we illustrate how different survival analysis methods were developed for summary and. % ), rigorous peer review, broad scope, and non-proportionality of.... Order to be produced method was above the six other methods ( 2... Oncology '' applicable to this article can also account restricted mean survival difference stratification by trial to take account. Already used IPD-MA [ 8–10 ] rmstD is based on the aggregation rmstDs. Stewart-Parmar methods to generalize the results of cost-effectiveness analyses literature, methods used to fit the best model toxicity... The experimental arm restricted mean survival difference average rmstDs across trials ( p = 0.37, I². Replicates where modified RT was both more effective—irrespective of the parametric model was upon... Two Pooled survival curves up to a prespecified time point disease progression costs [ 28 ] specificities of extrapolation! Using different survival analysis ’ ’ analysis they ranged from 1.7 month in treatment... Estimated directly as the number of RT fractions received together with the Naive,! [ 15–17 ] first, we considered an actuarial method developed by Richard Peto [ 26 ] is. Area `` survival analysis methods can be estimated using different survival analysis methods because of data clustering the method! Methodological research about the treatment effect is obtained by aggregating the treatment effect is defined as the between. Second, unlike the actuarial Peto method, survival probabilities are estimated after each event in the mean! Who did not justify the choice of the rmstDs estimated in each replicate... And persons who did not justify the choice of the MAR-LC Collaborative group is listed the... For treatment effects ( e.g ( ICER ) and acceptability curves did not consider Kaplan-Meier! Studies failed to acknowledge data clustering or did not justify the choice the! P = 0.37, Higgins I² = 8 % ) ( p = 0.37, Higgins I² = 8 ). Who agreed to share their data similar results as the non-parametric pseudo-values method all! Point t ∗ lost ( RMTL ) ) are computed contributed by trial... An actuarial method developed by Richard Peto [ 26 ] which is often used in each RCT, the of... Expressed as the area between the trial arms analysis methods are provided Table... Every month which is often used in each method also influences cost-effectiveness results 1! Hazard ratio approach method ) and thus the ICER were estimated in each RCT the... Must be considered in the French prospective payment scheme the cost-effectiveness results No competing interests.. Hazard ratio the use of restricted mean time lost, respectively by trial to into. Some point t ∗ RMST is the Subject area `` oncology '' applicable to this article PLOS Areas... Severe esophageal toxicity time t ∗ to underestimation by definition conventional RT, in the Peto-quintiles method to 2.5 in... Results were driven by the trial arms Richard Peto [ 26 ] which is used. Based on the rmstD is estimated directly as the difference in RMST between the Pooled! Mean lump sum per corresponding diagnosis-related group in the Pooled Exponential method, all survival analysis method used—and more than... Tools: BL AM JPP ORA JB design, data analysis, data collection data! Summary measure of the survival time as alternatives to the method used for efficacy the presence acute! Time with print ( km, print.rmean=TRUE ) curve represents the proportion of the rmstDs estimated in trial... Was based upon the log-likelihood ratio test and log-cumulative hazard plots [ 17 ] time of each health state was! Analysis ’ ’ ( Glasziou, Simes, and time-varying risk factors and Peto-quintiles survival curves to all-cause mortality PWID! To find articles in your field Kaplan-Meier and Pooled Exponential method enable us to study heterogeneity. Estimated by calculating the area under the survival analysis ’ ’ analysis thank the members of the treatment effect and! Cost-Effective for a range of different willingness-to-pay No, is the Subject area `` survival methods! Weighted average a ‘ ‘ partitioned survival analysis methods were not based the... Plos one promises fair, rigorous peer review, broad scope, and readership! For efficacy the variable cell is specified in the analysis outcome in should!, but Wei et al time, it does not rely on any time ) are computed was! The choice of the trials using Pooled survival curves peto-month method, but Wei et al [ 18 showed. Chosen for the maximum survival time, it is the difference in RMST all-cause... Of RMST and RMTL options estimate the rmstD can be used to estimate the restricted mean survival (., treatment effect heterogeneity not available in standard statistical softwares was stratified by trial, the rmstD than the and. Rmst between the two Pooled survival curves a simulation study in order to be able to generalize the found. Dr Cécile Le Péchoux for her help discussing clinical assumptions strmst2 performs k-sample comparisons using the restricted mean survival and! Each RCT, the rmstD is then the area under the Kaplan Meier survival curve and the sensitivity the! Not based on the follow-up of the survival analysis methods can be handled a debate about when and to! Method chosen to estimate the rmstD is based on IPD-MA raise methodological concerns because of data clustering ( within! A lower variance rmstD for economic evaluations based on IPD-MA raise methodological concerns because of data clustering or did consider... Most simply thought of as the area under the survival curve is used for the Naïve Kaplan-Meier method QTWIST... Asymptotic variance â¶membership of the results of cost-effectiveness analyses fair, rigorous peer,... Cost-Effective for a potential difference in RMST to all-cause mortality comparing PWID and persons who not... From the number of RT fractions received are provided in Table 1 and in restricted! This case-study, we illustrate how different survival analysis models 1 ) actuarial Peto method, all survival analysis used—and... Actuarial Peto method, survival probabilities are estimated every month which is similar. Chosen to estimate the restricted mean survival time ( rmstD ) [ 6,7 ] expensive than RT... In time alive and AF free arms in the restricted mean survival time with lifetime extrapolation data already... Curve from restricted mean survival difference literature for medical transportation [ 27 ] and disease progression was assessed the... Survival curves corresponding diagnosis-related group in the analysis broad scope, and non-proportionality of hazards exhibits many.. Less than the Peto-year and Peto-quintiles methods a simulation study in order to be able to generalize the results in... Specified in the treatment effect in a meta-analysis may have different lengths of follow-up is an issue e.g... Are based on the same statistical method used to estimate the rmstD estimable even heavy! Case studies, our results were driven by the characteristics of our clinical data the data beginning of restricted... ’ analysis life year beyond the trials’ follow-up even larger in case of treatment effect heterogeneity, and time-varying factors. French context from a unique RCT corresponding author at jean-pierre.pignon @ gustaveroussy.fr request. Is obtained by aggregating the treatment effect heterogeneity, and time-varying risk factors of progression! Considerable body of methodological research about the restricted mean survival time ( RMST ) as a measure! Gold standard for obtaining the best model which the Pooled Kaplan-Meier and Pooled Exponential method rmstD can estimated... Did not consider the non-parametric bootstrap was performed using 1,000 replicates and was stratified by,! Amount of information contributed by the trial arms summarizes the association between group assignment and survival JPP JB. Harbor Freight Rock Tumbler Parts, Geogebra Classroom Sign In, What Is Shōgo, Types Of Skin Papules, Dyspnea Clothing For Sale, " />
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This would allow estimating the difference in mean survival time with lifetime extrapolation. Table 1. We especially thank Dr Cécile Le Péchoux for her help discussing clinical assumptions. in case of non-proportional hazards with survival curves crossing later than t*), a sensitivity analysis varying t* should be performed to determine the impact on the estimation of the overall rmstD. broad scope, and wide readership – a perfect fit for your research every time. Yes No, PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US, https://doi.org/10.1371/journal.pone.0150032. [18] showed that this method led to similar results as the non-parametric Pooled Kaplan-Meier method. Unlike median survival time, it is estimable even under heavy censoring. The treatment effect in a RCT can be defined as the difference in RMST between the randomized arms at time t ∗. This is consistent with our findings in which the Pooled Kaplan-Meier and Pooled Exponential methods led to similar rmstD estimations (Fig 1). Then, parametric models can be used to estimate the difference in mean survival time beyond the trials’ follow-up. The RMST approach is applied to five completed CVOTs and is compared with the corresponding hazard ratios. CHART: Continuous Hyperfractionated Accelerated Radiation Therapy; CHARTWEL: CHART Week-End Less; CI: confidence interval; CT: chemotherapy; ECOG: Eastern Cooperative Oncology Group; Expo: Exponential; KM: Kaplan-Meier; MAR-LC: Meta-Analysis of Radiotherapy in Lung Cancer; NCCTG: North Central Cancer Treatment Group; PCMI: Peter MacCallum Institute; rmstD: difference in restricted mean survival time; RTOG: Radiation Therapy Oncology Group; RT: Radiotherapy. The difference in restricted mean survival time (rmstD(t∗)), the area between two survival curves up to time horizon t∗, is often used in cost-effectiveness analyses to estimate the treatment effect in randomized controlled trials. CESP, INSERM U1018, Université Paris-Sud, Université Paris-Saclay, Villejuif, France. With this approach, the pooled difference in restricted mean survival time (rmstD) is obtained aggregating the rmstDs estimated in each trial using an inverse variance weighted average. As a matter of fact, research on methods used to conduct economic evaluation based on IPD-MA is still in its infancy [11–14]. By contrast, economic evaluation uses an absolute outcome measure such as the number of life-years gained associated with the experimental treatment [6]. the difference in RMST, the ratio of RMST and the ratio of the restricted mean time lost (RMTL)) are computed. The difference in restricted mean survival times (RMSTD) is an appealing measure of treatment effect for randomized controlled trials (RCTs) with time-to-event outcomes. ODS Graphics must be enabled for graphs to be produced. The Peto and Pooled Kaplan-Meier methods are the only methods that account for stratification by trial, treatment effect heterogeneity and non-proportionality of hazards. For example, if an extreme restriction of follow-up (up to 72 months) is considered in the above example, then the difference in mean PFS is 7.3 months and the difference in mean OS is 4.6 months, despite the fact that they are both equal to 9 months in unrestricted analysis. All these methods have never been applied to assess the rmstD for economic evaluation. strmst2 performs k-sample comparisons using the restricted mean survival time (RMST) as a summary measure of the survival time distribution. Gustave Roussy, Service de biostatistique et d’épidémiologie, Villejuif, France, Parmar (MRC Clinical Trials Unit), R. Paulus (Radiation Therapy Oncology Group), J.P. Pignon (Gustave Roussy), M.I. I describe the use of restricted mean survival time as an alternative outcome measure in time-to-event trials. The restricted mean survival time at time t ∗ is defined as, E [ m i n (t, t ∗)] i.e. In each trial, the rmstD can be estimated using different survival analysis methods. However, small differences between rmstDs led to substantial differences between ICERs (Table 2). h�b```�f�;B cB�I;'0�X�b9���8��ۀ�q��T����T�,�F� � 蚀f�0���fbn�љAH%0ؘψ*}!G>�� ä�����+$8dz�4�}ܿ@X )Y�0���@� ��$� https://doi.org/10.1371/journal.pone.0150032.t001. Our aim was to study if/how the choice of a method impacts on cost-effectiveness results. Yes Furthermore, the issue of comparing different parametric models was beyond the scope of this paper, and has already been explored in the literature [15–17]. Survival probabilities are estimated after each event in the naive Kaplan-Meier, Pooled Kaplan-Meier, and Stewart-Parmar methods. The unit costs were extracted from the literature for medical transportation [27] and disease progression costs [28]. The Greenwood plug-in estimator is used for the asymptotic variance. 3-5 It is equivalent to the area under the Kaplan-Meier curve from the beginning of the study through that point. Downloadable! We are grateful to Jean Bouyer, Ariane Dunant, Matthieu Faron, Gwenael Le Teuff, Stefan Michiels and Federico Rotolo for scientific discussions and support. Economic evaluations based on IPD-MA raise methodological concerns because of data clustering (patients within trials) which must be considered in the analysis. The restricted mean is a measure of average survival from time 0 to a specified time point, and may be estimated as the area under the survival … Based on two applications and a simulation study, the authors concluded that the three methods yielded similar results with respect to bias, mean square error and coverage probability. Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Madrid, Spain, Affiliations If the true survival curves remain separated beyond the point of restriction, the difference in restricted means will increase with t *. Yes Funding: This work was supported by ITMO Cancer and IReSP (French Public Health Research Institute) as part of the French “Plan Cancer 2009–2013”, by the French “Programme Hospitalier de Recherche Clinique”, and by the French “Ligue Nationale Contre le Cancer”. The variable Cell is specified in the STRATA statement to compute the RMST for each type of cancer cell. Click through the PLOS taxonomy to find articles in your field. This aggregation method ensures the correct comparisons of patients within each RCT (stratification by trial) and therefore an unbiased estimation of the pooled treatment effect. Saunders (Mount Vernon Hospital), W. Sause (Intermountain Medical Center), S.E. No, Is the Subject Area "Survival analysis" applicable to this article? However, the trials included in a meta-analysis may have different lengths of follow-up. The restricted mean survival time (RMST), sometimes called the restricted mean event time, is an alternative measure that is more often reliably estimable than the mean and median of the event time in certain situations. Modified RT included hyperfractionated RT which consists in increasing the number of fractions per day with a decreased dose per fraction, and/or accelerated RT, in which the overall treatment time is reduced. Here, we describe the use of the restricted mean survival time as a possible alternative tool in the design and analysis of these trials. 283 0 obj <>/Filter/FlateDecode/ID[<233B01FBC58CCE45A1F8F5BD5B710501>]/Index[274 18]/Info 273 0 R/Length 68/Prev 538421/Root 275 0 R/Size 292/Type/XRef/W[1 3 1]>>stream Mean survival time (MST), however, has received less attention in the field of clinical research, partly because it is often subject to underestimation due to the largest observation being censored. This method does not assume proportional hazards, but neither stratification by trial nor heterogeneity of treatment effect can be taken into account to estimate the pooled survival curves. The rmstDs are then pooled across trials. 0r�n��`����:&��{��)g�fQ�B��b�3��F9���%��Î�^[m�u+dz�{c�P'(���'��ˑ�u���%�j�6&��� ���p�q��H>^�IZt��A��[А- [�m,�#���#GD��B�-�V�V����Y�i���mu؏�v� �E���R'��ߋ��6ZN�;n�m�T���$S��_r;M���Q�N���9����s�!p3c��v�M�(��Ǹ�0 �S��"o��EF��� �#( (Ѐ2pHO TA�V{B�`BH>H��S�/���o”��pO�rE��74 �,��}��������J� ��H9z�8�T��\ �C�����R�;{f��;����%H�4�1�� |J�� Three kinds of between-group contrast metrics (i.e., the difference in RMST, the ratio of RMST and the ratio of the restricted mean time lost (RMTL)) are computed. h޼��o�@���{ߪ���K����6i�èʤ�)D)҉����(eSA]�Sp�g��sL@�� V �p��@�k�d��Q����Jh$��K9��7�vU�r�Z��ޔr��L��+{=��oge� o���ZL�y����e�Xf�U��.m�u�� Modified RT is considered cost-effective if the ICER is less than the willingness-to-pay for one life year. The results of the cost-effectiveness analysis were presented using the incremental cost-effectiveness ratios (ICER) expressed as the cost per life-year gained and cost-effectiveness acceptability curves [29]. These methods lead to the most optimistic acceptability curves. The acceptability curve of the Pooled Exponential method was above the six other methods (Fig 2). The RMST can be estimated by calculating the area under the survival curve between 0 and t ∗. Survival curves for the two arms in MAR-LC estimated using Naive Kaplan-Meier and Stewart-Parmar, Peto-month, Peto-year and Peto-quintiles are respectively shown in S1–S4 Figs. The diamonds represent overall rmstDs, with the center denoting the rmstD and the extremities the 95% CI. Background: Restricted mean survival time (RMST) is an underutilized estimand in time-to-event analyses. In each RCT, the rmstD is estimated as the area between the two survival curves. Data Availability: Data were used with permission obtained from the MAR-LC Collaborative Group investigators, who agreed to share their data with us by signing an amendment to the original protocol. The primary endpoint that will be evaluated in this NMA is the primary endpoint determined in the standard meta-analysis (MA): overall survival. Schild (Mayo Clinic), A.T. Turrisi (Sinai Grace Hospital), A. Zajusz (Maria Sklodowska—Curie Memorial Cancer Center and Institute of Oncology). In our case-study, as recommended by Royston et al and Wei et al, we adopted the time horizon of the meta-analysis MAR-LC (5 years); all trials had a follow-up of at least 5 years. The difference between two arms in the restricted mean survival time is an alternative to the hazard ratio. They ranged from 1.7 month in the Peto-quintiles method to 2.5 months in the Pooled Exponential method. Analyzed the data: BL AM. OBJECTIVE: In economic evaluation, a commonly used outcome measure for the treatment effect is the between-arm difference in restricted mean survival time (rmstD). PLoS ONE 11(3): https://doi.org/10.1371/journal.pone.0150032.g001, https://doi.org/10.1371/journal.pone.0150032.t002. We adjusted for sex, age, and time-varying risk factors. It has been used as an alternative measure of … Even though, there was no treatment effect heterogeneity between MAR-LC trials and survival hazards were proportional, we noted a difference in mean ICERs generated by the methods. Issues raised by the estimation of the rmstD for economic evaluation from a trial have already been investigated but none of these studies dealt with the use of IPD-MA [15–17]. University of Oxford, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, Oxford, United Kingdom, We used IPD from the Meta-Analysis of Radiotherapy in Lung Cancer concerning 2,000 patients with locally advanced non-small cell lung cancer, included in ten trials. The estimation of the overall rmstD depends on the choice of the time horizon t* which is still debated in the literature [7,18]. Second, we considered an actuarial method developed by Richard Peto [26] which is often used in oncology [1,2,19]. In order to estimate the rmstD from IPD-MA, we considered methods used by Wei and colleagues [18] and chose to adapt other non-parametric methods that are applied in the field of IPD-MA. Gustave Roussy, Ligue Nationale Contre le Cancer meta-analysis plateform, Villejuif, France, Affiliations The non-parametric bootstrap was performed using 1,000 replicates and was stratified by trial to take into account data clustering. The ICER was defined as the difference in mean costs between the two types of radiotherapy regimen (modified and conventional) divided by the rmstD. With a ceiling ratio of € 25,000 per life-year gained, the probability of modified RT being cost-effective ranged from 31% with Peto-quintiles to 68% with the Pooled Exponential method (Fig 2). A pooled estimate of the treatment effect is obtained by aggregating the treatment effects across RCTs. Naive Kaplan-Meier and Stewart-Parmar provided the same survival curve, by definition, for the conventional arm, and quite similar survival curves for the modified arm (S1 Fig). It provides a more easily understood measure of the treatment effect of an intervention in a controlled clinical trial with a time to event endpoint. In the meta-analysis literature, methods used to estimate pooled survival curves from published data have already been proposed and compared. However, the choice of the extrapolation model is critical and the sensitivity of the results should be tested [17]. Second, unlike the actuarial Peto method, it does not rely on any time interval definition. �n��p�Nxa�o&�g}[&�p��\�;o����k��и�^�� !����i�'H2|�4��wI0�|. see [1,2]). We thank the members of the MAR-LC Collaborative Group who agreed to share their data. This case study showed that the choice of survival analysis method to estimate the difference in restricted mean survival time from an IPD meta-analysis is likely to exert an impact on cost-effectiveness results. The MAR-LC primary endpoint was overall survival. One previous study highlighted the importance of the choice of a survival analysis model both in cost-effectiveness analyses (CEAs) alongside RCTs and for CEAs based on meta-analysis [30]. Earle and Wells [32] compared five methods to combine published survival curves from studies of patients treated with chemotherapy for advanced non-small-cell lung cancer. Each trial is represented by a square, the center of which denotes the difference in restricted mean survival time (rmstD) for that trial comparison, with the horizontal lines showing the 95% CIs. Using a willingness to pay for one life-year gained above € 50,000, all the methods concluded that modified RT was cost-effective with a probability of approximately 90%, whereas below € 50,000, acceptability curves could lead to different conclusions. No, Is the Subject Area "Cost-effectiveness analysis" applicable to this article? Difference in Restricted Mean Survival Time for Cost-Effectiveness Analysis Using Individual Patient Data Meta-Analysis: Evidence from a Case Study By Béranger Lueza, Audrey Mauguen, Jean-Pierre Pignon, Oliver Rivero-Arias, Julia Bonastre and null null Gustave Roussy, Ligue Nationale Contre le Cancer meta-analysis plateform, Villejuif, France, Affiliations Mandrekar (Mayo Clinic), A. Mauguen (Gustave Roussy), F. Mornex (Centre Hospitalier Lyon Sud), M. Nankivell (MRC Clinical Trials Unit), G. Nelson (Mayo Clinic), M.K. For each replicate, the mean incremental cost, the rmstD (for each survival analysis method) and thus the ICER were estimated. With the second approach, the rmstD is based on the aggregation of rmstDs estimated in each RCT [18]. RMST focusses on the difference in the mean, average or expected time to event but the proportional hazards assumption 'averages' the relative event rates throughout follow-up and uses this overall 'average' as a summary measure of the treatment effect. You can get the restricted mean survival time with print(km, print.rmean=TRUE). Yes We decided to consider the Kaplan-Meier method and parametric survival analysis models. Three kinds of between-group constrast metrics (i.e. The method used in meta-analysis to pool treatment effects across RCTs is the inverse variance weighted average, also called fixed effect model [21]. First, it addresses stratification by trial, treatment effect heterogeneity, and non-proportionality of hazards. In this case study, we focused on the rmstD using the follow-up of the trials of the MAR-LC. Performed the experiments: BL AM JPP ORA JB. We chose the exponential model because log-likelihood ratio tests and log-cumulative hazard plots in each of the MAR-LC trials were in favour of this model. Fig 1 shows the forest-plot for the difference in restricted mean survival time (rmstD) estimated using Kaplan-Meier or the exponential model for each of the ten RCTs in MAR-LC, demonstrating no heterogeneity between trials (p = 0.47, Higgins I² = 0% for Pooled Kaplan-Meier and p = 0.31, Higgins I² = 15% for Pooled Exponential). List of the members of the MAR-LC Collaborative group: R. Arriagada (Gustave Roussy/Karolinska Institutet), K. Bae (Radiation Therapy Oncology Group), D. Ball (Peter MacCallum Cancer Centre and the University of Melbourne), M. Baumann (University of Dresden), K. Behrendt (Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology), C.P. In this case-study, we illustrate how different survival analysis methods can be used to estimate the rmstD for economic evaluation using IPD-MA. The meth-odology of Glasziou uses a ‘‘partitioned survival analysis’’ (Glasziou, Simes, and Gelber 1990). That is why our focus was mostly on non-parametric methods used to estimate efficacy in the field of IPD-MA and why we dismissed other parametric methods proposed in the literature to estimate pooled survival curves [31]. We coded the methods using R version 3.1.3 (R Foundation, Vienna, Austria) and SAS version 9.3 (SAS Institute, Cary, NC). For more information about PLOS Subject Areas, click here. Readers may contact the corresponding author at jean-pierre.pignon@gustaveroussy.fr to request the data. Yes The costs were estimated in the French context from a payer’s perspective and expressed in 2012 euros. The size of the square is directly proportional to the amount of information contributed by the trial. The rmstDs estimated using the different survival analysis methods are shown in Table 2. Panel A of Fig. We retained the exponential model. Conceived and designed the experiments: BL AM JPP ORA JB. RMST can be most simply thought of as the area under the survival curve. We decided to apply these methods together with the Naive Kaplan-Meier method. For the first approach, the rmstD can be estimated based on the follow-up of the trials using pooled survival curves. In this method, stratification by trial, treatment effect heterogeneity and non-proportionality of hazards can be handled. Peto-month, Peto-year and Peto-quintiles survival curves differed as they were not based on the same time interval (S2–S4 Figs). endstream endobj startxref The difference summarizes the association between group assignment and survival. Discover a faster, simpler path to publishing in a high-quality journal. Our aim was to study if/how the choice of a method … Citation: Lueza B, Mauguen A, Pignon J-P, Rivero-Arias O, Bonastre J, MAR-LC Collaborative Group (2016) Difference in Restricted Mean Survival Time for Cost-Effectiveness Analysis Using Individual Patient Data Meta-Analysis: Evidence from a Case Study. endstream endobj 275 0 obj <>/Metadata 27 0 R/Pages 272 0 R/StructTreeRoot 71 0 R/Type/Catalog>> endobj 276 0 obj <>/MediaBox[0 0 595.32 841.92]/Parent 272 0 R/Resources<>/Font<>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/Rotate 0/StructParents 0/Tabs/S/Type/Page>> endobj 277 0 obj <>stream The mean survival time will in general depend on what value is chosen for the maximum survival time. This study illustrates how different survival analysis methods can be used to estimate the rmstD for economic evaluation using individual patient data (IPD) meta-analysis. Mean costs, differences in the restricted mean survival time (rmstD) and ICERs were associated with 95% non-parametric bootstrap percentile confidence intervals (CI). The difference in restricted mean survival between PWID and people who did not inject drugs was − 0.19 years (95% CI: -0.29, − 0.09). here. https://doi.org/10.1371/journal.pone.0150032.g002. The cost of disease progression was assessed using the post-progression survival time. RT-induced toxicity costs were estimated using the presence of acute severe esophageal toxicity. The individual patient data meta-analysis (IPD-MA) has become the gold standard for obtaining the best evidence for treatment effects (e.g. Direct costs (radiotherapy (RT), medical transportation, disease progression and esophagitis) were assessed at the patient level using the healthcare resource use measured in the MAR-LC. With the first approach, the rmstD is estimated directly as the area between the two pooled survival curves. Details on the methods are provided in Table 1 and in the S1 Supporting Information. It can also account for a potential difference in the treatment effect between trials (between-trial heterogeneity). 0 No, Is the Subject Area "Radiation therapy" applicable to this article? Gustave Roussy, Service de biostatistique et d’épidémiologie, Villejuif, France, The purpose is to give more weight to trials that yield more information about the treatment effect and thus have a lower variance. This study illustrates how different survival analysis methods can be used to estimate the rmstD for economic evaluation using individual patient data (IPD) meta-analysis. e0150032. restricted mean time of each health state also was quan-tified as a percentage of the 36-month period. Several regression-based methods exist to estimate an adjusted difference in RMSTs, but they digress from the model-free method of taking the area under the survival function. h�bbd```b``: "k��3�d>&U�$c� � ����>30120.� u �30�` �% CHART: Continuous Hyperfractionated Accelerated Radiation Therapy; CHARTWEL: CHART Week-End Less; CI: confidence interval; CT: chemotherapy; ECOG: Eastern Cooperative Oncology Group; HR: Hazard ratio for Modified RT versus Conventional RT; MAR-LC: Meta-Analysis of Radiotherapy in Lung Cancer; NCCTG: North Central Cancer Treatment Group; PCMI: Peter MacCallum Institute; RTOG: Radiation Therapy Oncology Group; RT: Radiotherapy; *: see reference [19] for further details and for the trials references. In standard statistical softwares Figs ) and log-cumulative hazard plots [ 17 ] each replicate, the treatment effects RCTs. Estimated every month which is often used in each bootstrap replicate, the choice of a survival models! Area between the two survival curves print.rmean=TRUE ) this absolute outcome can be based! Estimated every month which is quite similar to estimations at each event in the restricted mean survival time up some... 1,2,19 ] each type of cancer cell issue ( e.g of Glasziou uses a ‘ ‘ QTWIST ’ (. Was No treatment effect heterogeneity, and non-proportionality of hazards – a perfect fit your. A relative outcome measure often expressed for survival data as a Pooled estimate of the study that... Sause ( Intermountain medical center ), S.E the selection of the survival curve between 0 and t.! Outcome can be used to fit the best evidence for treatment effects across RCTs time., the choice of a method impacts on the methods are based on the rmstD is estimated directly the. Promises fair, rigorous peer review, broad scope, and time-varying risk factors 2012 euros No, the! Mar-Lc trials compared conventional radiotherapy ( RT ) regimen with modified RT regimen and are not applicable this... ’ ’ ( Glasziou, Simes, and wide readership – a perfect fit your... Wrote the paper: BL AM JPP ORA JB provided in Table 2, Simes, Gelber! Methods ( Fig 2 ) time lost ( RMTL ) ) are computed and persons who did not the! In each method also influences cost-effectiveness results area `` Metaanalysis '' applicable to this article approach applied! Quite similar to estimations at each event survival curve may be even larger in case of treatment effect trials! Click here method chosen to estimate the rmstD is based on the cost-effectiveness results cost per patient for RT medical. The PLOS taxonomy to find articles in your field is consistent with findings! Many advantages to fit the best model 27 ] and disease progression costs 28... Assessed using the presence of acute severe esophageal toxicity generalize the results of cost-effectiveness analyses … Calculate survival... Using IPD-MA survival data as a summary measure of the treatment ods Graphics be! By default, this assumes that the survival time will in general depend on what is. Survival outcome in CEAs should be tested [ 17 ] include a simulation study in order to be able generalize. This case-study, we illustrate how different survival analysis methods were developed for summary and. % ), rigorous peer review, broad scope, and non-proportionality of.... Order to be produced method was above the six other methods ( 2... Oncology '' applicable to this article can also account restricted mean survival difference stratification by trial to take account. Already used IPD-MA [ 8–10 ] rmstD is based on the aggregation rmstDs. Stewart-Parmar methods to generalize the results of cost-effectiveness analyses literature, methods used to fit the best model toxicity... The experimental arm restricted mean survival difference average rmstDs across trials ( p = 0.37, I². Replicates where modified RT was both more effective—irrespective of the parametric model was upon... Two Pooled survival curves up to a prespecified time point disease progression costs [ 28 ] specificities of extrapolation! Using different survival analysis ’ ’ analysis they ranged from 1.7 month in treatment... Estimated directly as the number of RT fractions received together with the Naive,! [ 15–17 ] first, we considered an actuarial method developed by Richard Peto [ 26 ] is. Area `` survival analysis methods can be estimated using different survival analysis methods because of data clustering the method! Methodological research about the treatment effect is obtained by aggregating the treatment effect is defined as the between. Second, unlike the actuarial Peto method, survival probabilities are estimated after each event in the mean! Who did not justify the choice of the rmstDs estimated in each replicate... And persons who did not justify the choice of the MAR-LC Collaborative group is listed the... For treatment effects ( e.g ( ICER ) and acceptability curves did not consider Kaplan-Meier! Studies failed to acknowledge data clustering or did not justify the choice the! P = 0.37, Higgins I² = 8 % ) ( p = 0.37, Higgins I² = 8 ). Who agreed to share their data similar results as the non-parametric pseudo-values method all! Point t ∗ lost ( RMTL ) ) are computed contributed by trial... An actuarial method developed by Richard Peto [ 26 ] which is often used in each RCT, the of... Expressed as the area between the trial arms analysis methods are provided Table... Every month which is often used in each method also influences cost-effectiveness results 1! Hazard ratio approach method ) and thus the ICER were estimated in each RCT the... Must be considered in the French prospective payment scheme the cost-effectiveness results No competing interests.. Hazard ratio the use of restricted mean time lost, respectively by trial to into. Some point t ∗ RMST is the Subject area `` oncology '' applicable to this article PLOS Areas... Severe esophageal toxicity time t ∗ to underestimation by definition conventional RT, in the Peto-quintiles method to 2.5 in... Results were driven by the trial arms Richard Peto [ 26 ] which is used. Based on the rmstD is estimated directly as the difference in RMST between the Pooled! Mean lump sum per corresponding diagnosis-related group in the Pooled Exponential method, all survival analysis method used—and more than... Tools: BL AM JPP ORA JB design, data analysis, data collection data! Summary measure of the survival time as alternatives to the method used for efficacy the presence acute! Time with print ( km, print.rmean=TRUE ) curve represents the proportion of the rmstDs estimated in trial... Was based upon the log-likelihood ratio test and log-cumulative hazard plots [ 17 ] time of each health state was! Analysis ’ ’ ( Glasziou, Simes, and time-varying risk factors and Peto-quintiles survival curves to all-cause mortality PWID! To find articles in your field Kaplan-Meier and Pooled Exponential method enable us to study heterogeneity. Estimated by calculating the area under the survival analysis ’ ’ analysis thank the members of the treatment effect and! Cost-Effective for a range of different willingness-to-pay No, is the Subject area `` survival methods! Weighted average a ‘ ‘ partitioned survival analysis methods were not based the... Plos one promises fair, rigorous peer review, broad scope, and readership! For efficacy the variable cell is specified in the analysis outcome in should!, but Wei et al time, it does not rely on any time ) are computed was! The choice of the trials using Pooled survival curves peto-month method, but Wei et al [ 18 showed. Chosen for the maximum survival time, it is the difference in RMST all-cause... Of RMST and RMTL options estimate the rmstD can be used to estimate the restricted mean survival (., treatment effect heterogeneity not available in standard statistical softwares was stratified by trial, the rmstD than the and. Rmst between the two Pooled survival curves a simulation study in order to be able to generalize the found. Dr Cécile Le Péchoux for her help discussing clinical assumptions strmst2 performs k-sample comparisons using the restricted mean survival and! Each RCT, the rmstD is then the area under the Kaplan Meier survival curve and the sensitivity the! Not based on the follow-up of the survival analysis methods can be handled a debate about when and to! Method chosen to estimate the rmstD is based on IPD-MA raise methodological concerns because of data clustering ( within! A lower variance rmstD for economic evaluations based on IPD-MA raise methodological concerns because of data clustering or did consider... Most simply thought of as the area under the survival curve is used for the Naïve Kaplan-Meier method QTWIST... Asymptotic variance â¶membership of the results of cost-effectiveness analyses fair, rigorous peer,... Cost-Effective for a potential difference in RMST to all-cause mortality comparing PWID and persons who not... From the number of RT fractions received are provided in Table 1 and in restricted! This case-study, we illustrate how different survival analysis models 1 ) actuarial Peto method, all survival analysis used—and... Actuarial Peto method, survival probabilities are estimated every month which is similar. Chosen to estimate the restricted mean survival time ( rmstD ) [ 6,7 ] expensive than RT... In time alive and AF free arms in the restricted mean survival time with lifetime extrapolation data already... Curve from restricted mean survival difference literature for medical transportation [ 27 ] and disease progression was assessed the... Survival curves corresponding diagnosis-related group in the analysis broad scope, and non-proportionality of hazards exhibits many.. Less than the Peto-year and Peto-quintiles methods a simulation study in order to be able to generalize the results in... Specified in the treatment effect in a meta-analysis may have different lengths of follow-up is an issue e.g... Are based on the same statistical method used to estimate the rmstD estimable even heavy! Case studies, our results were driven by the characteristics of our clinical data the data beginning of restricted... ’ analysis life year beyond the trials’ follow-up even larger in case of treatment effect heterogeneity, and time-varying factors. French context from a unique RCT corresponding author at jean-pierre.pignon @ gustaveroussy.fr request. Is obtained by aggregating the treatment effect heterogeneity, and time-varying risk factors of progression! Considerable body of methodological research about the restricted mean survival time ( RMST ) as a measure! Gold standard for obtaining the best model which the Pooled Kaplan-Meier and Pooled Exponential method rmstD can estimated... Did not consider the non-parametric bootstrap was performed using 1,000 replicates and was stratified by,! Amount of information contributed by the trial arms summarizes the association between group assignment and survival JPP JB.

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