Protocol adherence for continuously titrated interventions in randomized trials: an overview of the current methodology and case study View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-07-17

AUTHORS

F. Lauzier, N. K. Adhikari, A. Seely, K. K. Y. Koo, E. P. Belley-Côté, K. E. A. Burns, D. J. Cook, F. D’Aragon, B. Rochwerg, M. E. Kho, S. J. W. Oczkowksi, E. H. Duan, M. O. Meade, A. G. Day, F. Lamontagne,

ABSTRACT

BACKGROUND: The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration. DISCUSSION: Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75-80 mmHg) versus lower (60-65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for >4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence. CONCLUSIONS: In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated with between-arm separation, if it can be measured. More... »

PAGES

106

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12874-017-0388-3

DOI

http://dx.doi.org/10.1186/s12874-017-0388-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1090740749

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28716047


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45 definition of deviation
46 deviation
47 deviations varies
48 different definitions
49 different information
50 doses
51 frequency
52 frequency of measurement
53 function
54 hours
55 impact
56 information
57 interpretation
58 intervention
59 limitations
60 measurements
61 measures
62 methodology
63 metrics
64 multiple metrics
65 overview
66 pilot trial
67 potential deviations
68 potential protocol deviations
69 pressure targets
70 proportion
71 protocol
72 protocol adherence
73 protocol deviations
74 protocol deviations varies
75 randomized trials
76 range
77 reasons
78 recent trials
79 reporting
80 research
81 robust measure
82 separation
83 shock
84 specific case study
85 standard definition
86 study
87 target
88 terminology
89 therapy
90 titration
91 trials
92 trials of interventions
93 values
94 varies
95 vasopressor doses
96 vasopressor therapy
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