Contextual Factors in Rheumatology: A PhD Study within Biostatistics and Clinical Epidemiology

Sabrina Mai Nielsen

doi:10.21996/c5pe-ft04

Contextual Factors in Rheumatology: A PhD Study within Biostatistics and Clinical Epidemiology

Bidragets oversatte titel: Kontekstuelle faktorer i reumatologi: Et ph.d.-studie indenfor biostatistik og klinisk epidemiologi

Sabrina Mai Nielsen

KI, OUH, Forskningsenhed for Reumatologi (Odense)

Frederiksberg og Bispebjerg Hospital

Publikation: Afhandling › Ph.d.-afhandling

Abstract

Kontekstuelle faktorer (Eng. contextual factors) er vigtige for at få en dybere forståelse af resultaterne fra kliniske forsøg. Gennem det globale Outcome Measures in Rheumatology (OMERACT)-initiativ er der et presserende behov for vejledning i at identificere kontekstuelle faktorer, når der udvikles såkaldte core outcome sets (dvs. et minimum set af målinger der skal foretages i kliniske forsøg). Dette førte til dannelsen af OMERACT-arbejdsgruppen, Contextual Factors Working Group.

1. Først præciserede vi det overordnede formål for arbejdsgruppen og udviklede en forskningsplan (artikel I). Hovedformålet var at udvikle en operationel definition og vejledning i at håndtere kontekstuelle faktorer i forsøg indenfor reumatologi, når der udvikles core outcome sets. Derudover ønskede vi at udvikle et generisk sæt af vigtige kontekstuelle faktorer for reumatologiske forsøg.
2. Vi undersøgte forskellige forståelser af begrebet kontekstuelle faktorer (artikel II). Ved hjælp af semistrukturerede interviews med 12 forskere/klinikere og 7 patienter, samt kvalitativ indholdsanalyse af interviewdataene, fandt vi to overordnede temaer, der tilsammen beskriver fire forskellige typer af kontekstuelle faktorer, hvoraf tre var relevante indenfor OMERACT.
3. Vi udviklede en operationel definition af kontekstuelle faktorer (artikel III). Beskrivelserne for de tre typer blev finpudset, og vi gennemførte et Delphi-studie med 33 patienter og 128 klinikere/øvrige. Efter to Delphi-runder var der opnået konsensus. De tre faktortyper blev kaldt effect modifying -, outcome influencing - og measurement affecting contextual factors, som på dansk kan formidles som hhv. effekt-modificerende -, udfalds-influerende og målings-påvirkende kontekstuelle faktorer.
4. Vi undersøgte en række patientkarakteristika for, om de kunne ændre behandlingseffekten på tværs af forsøg indenfor reumatologi, og dermed ville være effect modifying contextual factors (artikel IV). Vi inkluderede 187 randomiserede forsøg i en meta-epidemiologisk undersøgelse og fandt begrænsede data og få, potentielt misvisende, indikationer på effektmodifikation.
5. Til sidst leverede vi en simpel vejledning i statistiske tests af interaktion til at identificere effektmodifikation (subgruppeeffekter) i randomiserede forsøg (artikel V). I vejledningen foreslår vi, at forsøgsrapporter i fremtiden skal estimere behandlingseffekten i forskellige subgrupper for at facilitere nuancerede opsummeringer af evidens, der på sigt kan fremme stratificeret patientbehandling.

Vores operationelle definition af kontekstuelle faktorer beskriver tre typer, effect modifying -, outcome influencing - og measurement affecting contextual factors. Vi undersøgte potentielle effect modifying contextual factors på tværs af forsøg, men fandt begrænset evidens, særligt på grund af manglende data. Der er behov for konsekvent og ensartet rapportering af patientkarakteristika i forsøg og gerne estimater for behandlingseffekten i subgrupper. Vores biostatistiske vejledning kan bruges som inspiration. Dette arbejde forventes at fortsætte som tre initiativer, for at udvikle en liste med vigtige faktorer og vejledning for hver type af de kontekstuelle faktorer.

Bidragets oversatte titel	Kontekstuelle faktorer i reumatologi: Et ph.d.-studie indenfor biostatistik og klinisk epidemiologi
Originalsprog	Engelsk
Bevilgende institution	Syddansk Universitet
Vejledere/rådgivere	Christensen, Robin, Hovedvejleder Ellingsen, Torkell, Vejleder Tugwell, Peter, Vejleder, Ekstern person Wells, George A, Vejleder, Ekstern person
Eksterne samarbejdspartnere	OMERACT
Udgiver	Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet
DOI	https://doi.org/10.21996/c5pe-ft04
Status	Udgivet - 13. jan. 2022

Bibliografisk note

Afhandlingen kan lånes på SDUs bibliotek.

Dokumenter og links

10.21996/c5pe-ft04

5 Tidsskriftartikel

Effect Modifiers and Statistical Tests for Interaction in Randomized Trials
Christensen, R., Bours, M. J. L. & Nielsen, S. M., jun. 2021, I: Journal of Clinical Epidemiology. 134, s. 174-177
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Åben adgang
Fil
34 Downloads (Pure)
OMERACT consensus-based operational definition of contextual factors in rheumatology clinical trials: A mixed methods study
Nielsen, S. M., Boers, M., de Wit, M., Shea, B., van der Windt, D. A., Reeves, B. C., Beaton, D., Alten, R., Toupin April, K., Boonen, A., Escorpizo, R., Flurey, C., Furst, D. E., Guillemin, F., Leong, A., Pohl, C., Rasmussen, M. U., Singh, J. A., Smolen, J. S., Strand, V., & 8 flereVerstappen, S. M. M., Voshaar, M., Woodworth, T. G., Ellingsen, T., March, L., Wells, G. A., Tugwell, P. & Christensen, R., jun. 2021, I: Seminars in Arthritis and Rheumatism. 51, 3, s. 601-606
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Åben adgang
Fil
67 Downloads (Pure)
Towards consensus in defining and handling contextual factors within rheumatology trials: An initial qualitative study from an OMERACT working group
Nielsen, S. M., Rasmussen, M. U., Boers, M., van der Windt, D. A., de Wit, M., Woodworth, T. G., Flurey, C. A., Beaton, D., Shea, B., Escorpizo, R., Furst, D. E., Smolen, J. S., Toupin-April, K., Boonen, A., Voshaar, M., Ellingsen, T., Wells, G. A., Reeves, B. C., March, L., Tugwell, P., & 1 flereChristensen, R., feb. 2021, I: Annals of the rheumatic diseases. 80, 2, s. 242-249
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Åben adgang
Fil
96 Downloads (Pure)

Citationsformater

@misc{7c391b7312834d04a9ee63315d49707a,

title = "Contextual Factors in Rheumatology: A PhD Study within Biostatistics and Clinical Epidemiology",

abstract = "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.",

author = "{Mai Nielsen}, Sabrina",

note = "The thesis can be borrowed from the SDU library. ",

year = "2022",

month = jan,

day = "13",

doi = "10.21996/c5pe-ft04",

language = "English",

publisher = "Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet",

school = "SDU",

}

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 -

Contextual Factors in Rheumatology: A PhD Study within Biostatistics and Clinical Epidemiology

Abstract

Bibliografisk note

Dokumenter og links

Fingeraftryk

Relaterede publikationer

Effect Modifiers and Statistical Tests for Interaction in Randomized Trials

OMERACT consensus-based operational definition of contextual factors in rheumatology clinical trials: A mixed methods study

Towards consensus in defining and handling contextual factors within rheumatology trials: An initial qualitative study from an OMERACT working group

Citationsformater