TY - JOUR
T1 - A first step towards best practice recommendations for the design and statistical analyses of pragmatic clinical trials
T2 - a modified Delphi approach
AU - Palin, Victoria
AU - Van Staa, Tjeerd P.
AU - Steels, Stephanie
AU - Troxel, Andrea B.
AU - Groenwold, Rolf H. H.
AU - MacDonald, Tom M.
AU - Torgerson, David
AU - Faries, Douglas
AU - Mancini, Pierre
AU - Ouwens, Mario
AU - Frith, Lucy J.
AU - Tsirtsonis, Kate
AU - MacLennan, Graham
AU - Nordon, Clementine
N1 - Funding Information:
Innovative Medicines Initiative. Grant Number: 807012
Copyright:
© 2022 British Pharmacological Society.
PY - 2022/12
Y1 - 2022/12
N2 - Aim: Pragmatic clinical trials (PCTs) are randomized trials implemented through routine clinical practice, where design parameters of traditional randomized controlled trials are modified to increase generalizability. However, this may introduce statistical challenges. We aimed to identify these challenges and discuss possible solutions leading to best practice recommendations for the design and analysis of PCTs. Methods: A modified Delphi method was used to reach consensus among a panel of 11 experts in clinical trials and statistics. Statistical issues were identified in a focused literature review and aggregated with insights and possible solutions from experts collected through a series of survey iterations. Issues were ranked according to their importance. Results: Twenty-seven articles were included and combined with experts' insight to generate a list of issues categorized into participants, recruiting sites, randomization, blinding and intervention, outcome (selection and measurement) and data analysis. Consensus was reached about the most important issues: risk of participants' attrition, heterogeneity of “usual care” across sites, absence of blinding, use of a subjective endpoint and data analysis aligned with the trial estimand. Potential issues should be anticipated and preferably be addressed in the trial protocol. The experts provided solutions regarding data collection and data analysis, which were considered of equal importance. Discussion: A set of important statistical issues in PCTs was identified and approaches were suggested to anticipate and/or minimize these through data analysis. Any impact of choosing a pragmatic design feature should be gauged in the light of the trial estimand.
AB - Aim: Pragmatic clinical trials (PCTs) are randomized trials implemented through routine clinical practice, where design parameters of traditional randomized controlled trials are modified to increase generalizability. However, this may introduce statistical challenges. We aimed to identify these challenges and discuss possible solutions leading to best practice recommendations for the design and analysis of PCTs. Methods: A modified Delphi method was used to reach consensus among a panel of 11 experts in clinical trials and statistics. Statistical issues were identified in a focused literature review and aggregated with insights and possible solutions from experts collected through a series of survey iterations. Issues were ranked according to their importance. Results: Twenty-seven articles were included and combined with experts' insight to generate a list of issues categorized into participants, recruiting sites, randomization, blinding and intervention, outcome (selection and measurement) and data analysis. Consensus was reached about the most important issues: risk of participants' attrition, heterogeneity of “usual care” across sites, absence of blinding, use of a subjective endpoint and data analysis aligned with the trial estimand. Potential issues should be anticipated and preferably be addressed in the trial protocol. The experts provided solutions regarding data collection and data analysis, which were considered of equal importance. Discussion: A set of important statistical issues in PCTs was identified and approaches were suggested to anticipate and/or minimize these through data analysis. Any impact of choosing a pragmatic design feature should be gauged in the light of the trial estimand.
KW - bias
KW - cluster-randomized trials
KW - effectiveness
KW - pragmatic clinical trials
KW - routine clinical practice
UR - http://www.scopus.com/inward/record.url?scp=85133739129&partnerID=8YFLogxK
U2 - 10.1111/bcp.15441
DO - 10.1111/bcp.15441
M3 - Article
C2 - 35701368
VL - 88
SP - 5183
EP - 5201
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
SN - 0306-5251
IS - 12
ER -