Framework for Implementing Individualised Dosing of Anti-Cancer Drugs in Routine Care: Overcoming the Logistical Challenges

Round 1

Reviewer 1 Report

This manuscript presents a general framework and six-step process to establish and implement personalized dosing of cancer drugs in routine care. Their framework covers four key phases and shows the importance of keeping all stakeholders engaged. Each step is sufficiently explained with alternative suggestions, which could contribute to others who are facing the same challenges of implementing individualized dosing. Despite the lack of final results from their current program in this manuscript, it is promising to see this guideline is successfully implemented to their day-to-day clinical practices.

I have a few minor suggestions that the authors might consider.

1. Line 75: the authors mentioned that “One method of individualised dosing is using therapeutic drug monitoring (TDM) with an adjustment dosing strategy”. Could you explain what is your adjustment dosing strategy? Foe instance, how you decide the starting dose and interval dose for different drugs.

2. Line 137: as it was written “We utilised a previously described criteria by the DPOG for identifying potential drug candidates for individualised dosing”. It would be helpful to clarify which drugs were chosen in your program based on DPOG criteria.

3. Line 205: “Blood collection can be performed at either a registered blood collection centre or an in-house facility supplied with the necessary consumables, equipment, and storage.” I am wondering how many samples of each patient and at what time interval (e.g., 4, 8, and 12 weeks after start of treatment) would the guideline suggests?

4. Figure 2. The title (Line 107) and content of figure (Communicate and Disseminate Outcomes to?) should be double checked.

5. For future studies:  have the authors considered applying the AI into the program? For example, there are algorithms developed for dosing optimizing and applied in oncology. Besides, the data and final results from this program could be an useful database for developing a new algorithm for further application.

Author Response

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Reviewer 2 Report

Van Leuven et al mscr is a well prepared work, with focused public health comments and thoughtful presentation.

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Reviewer 3 Report

The communication presented by Jason van Leuven and colleagues is focused on the Implementation strategies of 6-step processes.

In general, it is well written, except for different typos that can be found in the text. The figures should be more appealing and the manuscript is too general.

The authors talk about the 6 steps, without considering the different chemotherapeutics or drugs that can be used in the management of the patients.

At a point, in the text, they write:

 "such as everolimus (target concentration of ≥ 10 µg/L) [13-16], imatinib (≥ 1,100 µg/L) [17-23], sunitinib (≥ 37.5 µg/L with continuous dosing, ≥ 50 µg/L with intermittent dosing) [24,25], pazopanib (≥ 20,000 86 µg/L) [26-32] with several others, described in our recently published review [3]. Despite evidence showing a progression-free survival (PFS) or overall survival (OS) benefit, plasma concentration guided dosing of anti-cancer drugs has not been translated into clinical practice" graphics representing these sentences could be appreciated. 

Author Response

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