PONE-D-23-24800A pharmacist-led interprofessional medication adherence program improved adherence to oral anticancer therapies: The OpTAT randomized controlled trialPLOS ONE

Dear Dr. Bandiera,

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Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Abstract

1. The control arm received standard care plus EM without intervention. All PKIs were delivered in electronic monitors (EMs).

→ The control arm received standard care plus electronic monitor (EM) without intervention. All PKIs were delivered in EMs.

Introduction

1. Why is it necessary to investigate the adherence of protein kinase inhibitors (PKIs) in the context of solid tumors when the current body of literature has focused on their adherence in chronic myeloid leukemia (CML)? What justifies the need for a distinct examination of PKI adherence in solid tumors, and why can’t the findings from CML studies be directly extrapolated? Furthermore, what insights have previous studies provided regarding PKI adherence in CML? Incorporating these aspects into the introduction would help elucidate the significance of this study.

Methods

1. Could you explain your process for identifying and reaching out to potential pharmacists to obtain informed consent?

2. Which theoretical framework guided the study design and the selection of variables?

3. Could you please elaborate on the intervention process and the content that was implemented during the study?

4. What was the effect size and power of the study? How did you calculate and make sure the study sample size was large enough to have sufficient power for statistical analyses? Please provide more information to address these issues.

Results

1. Why did the two groups exhibit such a huge disparity in the median time spent on adherence after enrollment?

Discussion

1. Regarding medication implementation, the intervention benefited mostly men, patients younger than 60 years, patients prescribed PKIs longer than 60 days, patients without a diagnosis of metastasis or with a metastatic disease experience longer than 2 years, and patients who had never used any adherence tool in their therapeutic itinerary.

→ What could be the potential explanations for the factors identified in relation to medication implementation? Do the study findings align with the existing literature? You need to address these issues in the discussion section.

2. First, the OpTAT study explored adherence to PKIs among patients with advanced solid cancers,…

→ Was the cancer stage used as a criterion for participant recruitment? Without such criteria, making statements about advanced solid cancers may not be justified.

Reviewer #2: The study is rigorous, clear and accurate, I would however reformulate the hypothesis. The statements below are not clear and prone to confusion:

- We hypothesized that PKI implementation would be significantly lower if the alternate regimens (i.e., transient interruptions of PKI) prescribed by oncologists were not considered in the calculation

- Persistence would be improved

- These patients would perceive fewer prejudices and concerns about taking PKIs

Reviewer #3: This is a randomized clinical trial to evaluate the impact of a pharmacist-led interprofessional medication adherence program (IMAP) on patient implementation (dosing history), persistence (time until premature cessation of the treatment) and adherence to 27 PKIs prescribed for various solid cancers, as well as the impact on patients’ beliefs about medicines (BAM) and quality of life (QoL). The study included 118 patients who were randomized 1:1 into two arms. The study concluded that The IMAP, led by pharmacists in the context of an interprofessional collaborative practice, supported adherence, specifically implementation, to PKIs among patients with solid cancers. I have some concerns on the study design and statistical analysis.

1. The authors need to provide the sample size calculation and power analysis to justify the design of the study.

2. There are multiple testing that have been conducted in the study. However, there is no description on multiple comparison adjustment to avoid the inflation of false positive.

3. In Figure 5, there is no methodology description on how to generate the curves of the empirical implementation.

4. The major comparison is between the intervention and control groups, suggest removing the 9 patients of the not randomized from Table 1.

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Reviewer #1: No

Reviewer #2: Yes: Myriam Noelle Watfa

Reviewer #3: No

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A pharmacist-led interprofessional medication adherence program improved adherence to oral anticancer therapies: The OpTAT randomized controlled trial

PONE-D-23-24800R1

Dear Dr. Bandiera,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Mabel Aoun, MD, MPH

Academic Editor

PLOS ONE

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