TY - GEN
T1 - Contextual Factors in Rheumatology
T2 - A PhD Study within Biostatistics and Clinical Epidemiology
AU - Mai Nielsen, Sabrina
N1 - The thesis can be borrowed from the SDU library.
PY - 2022/1/13
Y1 - 2022/1/13
N2 - Contextual factors are important for understanding trial results. Through the global Outcome Measures in Rheumatology (OMERACT) initiative of international stakeholders interested in outcome measurements and trial design, there is an urgent need for guidance on how to identify contextual factors as part of core outcome set development. This led to the formation of the OMERACT Contextual Factors Working Group.First, we clarified the overall aim of the effort and developed a research plan (paper I). Our main goal was to provide an operational definition and guidance on how to address contextual factors in rheumatology trials as part of developing core outcome sets. Further, we aimed to provide a generic set of important contextual factors that should always be considered in rheumatology trials.Second, we explored perspectives on contextual factors (paper II). Through semi-structured interviews of 12 researchers/clinicians and 7 patients, and qualitative content analysis, we found two overarching themes describing four types of contextual factors, of which three were relevant within OMERACT.Third, we developed a consensus-based operational definition of contextual factors (paper III). We refined the descriptions of the three contextual factor types and involved 33 patients and 128 clinicians/others in a Delphi survey, reaching consensus after two rounds. The contextual factor types were termed effect modifying -, outcome influencing -, and measurement affecting contextual factors.Fourth, we explored whether population characteristics modify treatment response across trials within rheumatology and, hence, may be effect modifying contextual factors (paper IV). We included 187 trials in a meta-epidemiological study and found limited data and few, potentially spurious, indications of effect modification.Finally, we provided a concise and nontechnical (biostatistics) tutorial on the use of statistical tests for interaction to identify effect modifiers (subgroup effects) in randomized trials (paper V). We propose that trial reports in the future should include treatment effect estimates for subgroups to facilitate better evidence synthesis on stratified medicine.In conclusion, our consensus-based operational definition of contextual factors describes three types, effect modifying -, outcome influencing -, and measurement affecting contextual factors. When exploring potential effect modifying contextual factors across trials, we found limited evidence, mainly due to lack of data. There is an urgent need for consistent reporting of population characteristics in trials and, preferably, treatment effect estimates for subgroups. Our simple hands-on guide for investigating effect modifiers may be used as inspiration. This work is expected to continue as three separate workstreams for developing consensus-based generic lists of important factors and guidance for each contextual factor type.
AB - Contextual factors are important for understanding trial results. Through the global Outcome Measures in Rheumatology (OMERACT) initiative of international stakeholders interested in outcome measurements and trial design, there is an urgent need for guidance on how to identify contextual factors as part of core outcome set development. This led to the formation of the OMERACT Contextual Factors Working Group.First, we clarified the overall aim of the effort and developed a research plan (paper I). Our main goal was to provide an operational definition and guidance on how to address contextual factors in rheumatology trials as part of developing core outcome sets. Further, we aimed to provide a generic set of important contextual factors that should always be considered in rheumatology trials.Second, we explored perspectives on contextual factors (paper II). Through semi-structured interviews of 12 researchers/clinicians and 7 patients, and qualitative content analysis, we found two overarching themes describing four types of contextual factors, of which three were relevant within OMERACT.Third, we developed a consensus-based operational definition of contextual factors (paper III). We refined the descriptions of the three contextual factor types and involved 33 patients and 128 clinicians/others in a Delphi survey, reaching consensus after two rounds. The contextual factor types were termed effect modifying -, outcome influencing -, and measurement affecting contextual factors.Fourth, we explored whether population characteristics modify treatment response across trials within rheumatology and, hence, may be effect modifying contextual factors (paper IV). We included 187 trials in a meta-epidemiological study and found limited data and few, potentially spurious, indications of effect modification.Finally, we provided a concise and nontechnical (biostatistics) tutorial on the use of statistical tests for interaction to identify effect modifiers (subgroup effects) in randomized trials (paper V). We propose that trial reports in the future should include treatment effect estimates for subgroups to facilitate better evidence synthesis on stratified medicine.In conclusion, our consensus-based operational definition of contextual factors describes three types, effect modifying -, outcome influencing -, and measurement affecting contextual factors. When exploring potential effect modifying contextual factors across trials, we found limited evidence, mainly due to lack of data. There is an urgent need for consistent reporting of population characteristics in trials and, preferably, treatment effect estimates for subgroups. Our simple hands-on guide for investigating effect modifiers may be used as inspiration. This work is expected to continue as three separate workstreams for developing consensus-based generic lists of important factors and guidance for each contextual factor type.
U2 - 10.21996/c5pe-ft04
DO - 10.21996/c5pe-ft04
M3 - Ph.D. thesis
PB - Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet
ER -