A review of studies examining the relationship between progression ...

More documents

Recommendations

Info

effect on PFS and treatment effect on OS with three using individual patient data, whilst theremainder used aggregate data from multiple trials. A variety of statistical techniques were employedwithin these studies, with the most commonly used being rank correlation coefficients, linearregression and landmark analysis. The lack of a standardised approach made it difficult to establishwhether there is a consistent relationship between PFS/TTP and OS. The majority of the studiesfound a positive correlation between PFS/TTP and OS for individual patients, individual trial armsand the treatment effect between trial arms, although, the size of the correlation and its statisticalsignificance varied considerably across studies. This is not surprising given the variety of methodsemployed and the variation in studies characteristics such as differences in the tumour type and theline of therapy considered.ConclusionThis review suggests that the level of evidence available supporting a relationship between PFS/TTPand OS varies considerably by cancer type and is not always consistent even within one specificcancer type. Furthermore, even where strong consistent evidence supporting a correlation betweenthe treatment effects (i.e Level 1 evidence according to Elston and Taylor’s framework) is available,it is unclear how that should be converted into a quantified relationship between PFS and OStreatment effects within a cost-effectiveness model. Therefore, any cost-effectiveness analysis whichmakes a strong assumption regarding the relationship between PFS and OS should be treated withcaution. We would support Elston and Taylor in recommending that any cost-effectiveness analysisbased on a surrogate relationship between PFS and OS should be supported with a transparentexplanation of how the relationship is quantified in the model and should be accompanied bysensitivity analysis exploring the uncertainty associated with that relationship and a systematicreview of papers examining the relationship between PFS and OS in the relevant setting. This wouldallow decision makers to judge the appropriateness of the model in light of the evidence available inthat specific disease area.4
CONTENTS1. INTRODUCTION ............................................................................................................... 71.1. BACKGROUND ..................................................................................................................... 71.2. RELEVANCE OF PFS/TTP AND OS OUTCOMES TO COST-EFFECTIVENESS ANALYSIS ................ 71.3. QUANTIFYING THE RELATIONSHIP BETWEEN PFS AND OS IN COST-EFFECTIVENESS MODELS .. 81.4. EVALUATING THE RELATIONSHIP BETWEEN PFS/TTP AND OS .............................................. 92. REVIEW METHODS........................................................................................................ 112.1. SEARCH STRATEGY ........................................................................................................... 112.2. INCLUSION CRITERIA ......................................................................................................... 113. STUDY CHARACTERISTICS ......................................................................................... 124. STUDIES EXAMINING THE RELATIONSHIP BETWEEN OUTCOMES FORINDIVIDUALS OR SINGLE TREATMENT ARMS ............................................................. 214.1. METHODS IN STUDIES USING AGGREGATE DATA FROM MULTIPLE TRIALS ............................. 214.2. METHODS IN STUDIES USING INDIVIDUAL PATIENT DATA .................................................... 224.3. RESULTS ........................................................................................................................... 224.3.1.Results from studies using aggregate data from multiple trials........................................ 224.3.2 Results from studies examining individual level correlations........................................... 235. STUDIES EXAMINING THE RELATIONSHIP BETWEEN THE TREATMENTEFFECT FOR PFS/TTP AND THE TREATMENT EFECT FOR OS ACROSS MULTIPLERCTS ......................................................................................................................................... 235.1. DEFINITION OF TREATMENT EFFECT ................................................................................... 245.2. REGRESSION METHODS ...................................................................................................... 245.3. OTHER MEASURES OF CORRELATION BETWEEN THE TREATMENT EFFECTS ........................... 265.4. RESULTS ........................................................................................................................... 275.4.1 Regression parameters ................................................................................................... 275.4.2 Modifying factors examined in multivariate or subgroup analysis ................................... 285.4.3 Validation of predictive relationships ............................................................................. 285.4.4 Correlation coefficients .................................................................................................. 295.4.5 Indirect information based on the relationship between TTP and PPS ............................ 296. DISCUSSION ..................................................................................................................... 326.1. CONSISTENCY OF METHODS USED ............. …………………………………………………326.2. LEVEL OF EVIDENCE IN DIFFERENT TUMOUR TYPES…………………………………………326.3. LIMITATIONS OF THE EVIDENCE AVAILABLE .......... …………………………………………326.4. LIMITATIONS OF THIS REVIEW ............................... …………………………………………337. CONCLUSIONS ................................................................................................................ 348. REFERENCES .................................................................................................................. 359. APPENDICES .................................................................................................................... 385
Page 1 and 2: A REVIEW OF STUDIES EXAMINING THE R
Page 3: EXECUTIVE SUMMARYIntroductionProgre
Page 7 and 8: 1. INTRODUCTION1.1. BACKGROUNDProgr
Page 9 and 10: equivalent incremental benefit in O
Page 11: 2. REVIEW METHODS2.1. SEARCH STRATE
Page 14 and 15: Table 1: Characteristics of include
Page 16 and 17: Table 2: Methods used to analyse th
Page 18 and 19: Reference Data type Relationships a
Page 20 and 21: Reference Data type Relationships a
Page 22 and 23: 4.2. METHODS IN STUDIES USING INDIV
Page 24 and 25: 5.1. DEFINITION OF TREATMENT EFFECT
Page 26 and 27: 5.3. OTHER MEASURES OF CORRELATION
Page 28 and 29: The slope parameters in the linear
Page 30 and 31: Table 4: Summary of results by tumo
Page 33 and 34: many of the papers included in this
Page 35 and 36: 8. REFERENCES1. Therasse, P., Arbuc
Page 37 and 38: 25. Hotta, K., Kiura, K., Fujiwara,
Page 39 and 40: APPENDIX 2: SEARCH STRATEGIESThe in
Page 41: 38 26 or 27 or 28 or 29 (1206968)39

A review of studies examining the relationship between progression ...

Create successful ePaper yourself

Delete template?

Save as template?