Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2016 Oct;47(10):2131-2137.
doi: 10.1016/j.injury.2016.07.028. Epub 2016 Jul 21.

Assessing protocol adherence in a clinical trial with ordered treatment regimens: Quantifying the pragmatic, randomized optimal platelet and plasma ratios (PROPPR) trial experience

Hongjian Zhu  1 , Erin E Fox  2 , Sarah Baraniuk  3 , John B Holcomb  2 , Charles E Wade  2 , Deborah J Del Junco  2 , Barbara C Tilley  3 ; PROPPR Study Group
Affiliations
Clinical Trial

Assessing protocol adherence in a clinical trial with ordered treatment regimens: Quantifying the pragmatic, randomized optimal platelet and plasma ratios (PROPPR) trial experience

Hongjian Zhu et al. Injury. 2016 Oct.

Abstract

Background: Medication dispensing errors are common in clinical trials, and have a significant impact on the quality and validity of a trial. Therefore, the definition, calculation and evaluation of such errors are important for supporting a trial's conclusions. A variety of medication dispensing errors can occur. In this paper, we focus on errors in trials where the intervention includes multiple therapies that must be given in a pre-specified order that varies across treatment arms and varies in duration.

Methods: The Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial was a Phase III multi-site, randomized trial to compare the effectiveness and safety of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with a 1:1:2 ratio. In this trial, these three types of blood products were to be transfused in a pre-defined order that differed by treatment arm. In this paper, we present approaches from the PROPPR trial that we used to define and calculate the occurrence of out of order blood transfusion errors. We applied the proposed method to calculate protocol adherence to the specified order of transfusion in each treatment arm.

Results: Using our proposed method, protocol adherence was greater in the 1:1:1 group than in the 1:1:2 group (96% vs 93%) (p<0.0001), although out of order transfusion errors in both groups were low. Final transfusion ratios of plasma to platelets to red blood cells for the 1:1:1 ratio group was 0.93:1.32:1, while the transfusion ratio for the 1:1:2 ratio group was 0.48:0.48:1.

Conclusions: Overall, PROPPR adherence to blood transfusion order pre-specified in the protocol was high, and the required order of transfusions for the 1:1:2 group was more difficult to achieve. The approaches proposed in this manuscript were useful in evaluating the PROPPR adherence and are potentially useful for other trials where a specific treatment orders with varying durations must be maintained.

Keywords: Blood product transfusion; Medication dispensing error; Ordered treatment regimens; Protocol adherence.

PubMed Disclaimer

Conflict of interest statement

Statement The authors have no declared conflicts of interest related to this manuscript.

Figures

Figure 1
Figure 1
Blood transfusion order in the Protocol of the PROPPR trial. Note: The left side is for the 1:1:1 group. The right side is for the 1:1:2 group. One dose of platelets represents a pool of six units and one dose of red blood cells or plasma represents one unit.
Figure 2
Figure 2
Box plot of error proportion by treatment
Figure 3
Figure 3
Relationship between error proportion and total number of transfused blood products
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Alexander JH, et al. Documentation of study medication dispensing in a prospective large randomized clinical trial: experiences from the ARISTOTLE Trial. American heart journal. 2013;166(3):559–565.e1. - PubMed
    1. James KL, et al. Incidence, type and causes of dispensing errors: a review of the literature. International journal of pharmacy practice. 2009;17(1):9–30. - PubMed
    1. SPENCER MG, SMITH AP. A multicentre study of dispensing errors in British hospitals. International Journal of Pharmacy Practice. 1993;2(3):142–146.
    1. Allan E, Barker K. Fundamentals of medication error research. American Journal of Health-System Pharmacy. 1990;47(3):555–571. - PubMed
    1. Holcomb JB, et al. Transfusion of plasma, platelets, and red blood cells in a 1: 1: 1 vs a 1: 1: 2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. Jama. 2015;313(5):471–482. - PMC - PubMed

Publication types

LinkOut - more resources