Evaluating the Indirect Costs of Care Associated with Salvage Chemotherapy for Relapsed and Refractory Aggressive-Histology Lymphoma: A Subset Analysis of the Canadian Cancer Trials Group (CCTG) LY.12 Clinical Trial

Round 1

Reviewer 1 Report

This is a very interesting study evaluating the indirect costs in patients treated on the LY.12 trial. It raises awareness as to the indirect costs experienced by patients with relapsed and refractory aggressive-histology lymphoma. The authors conclude that salvage chemotherapy for R/R aggressive NHL is associated with significant indirect costs to the patients and their caregivers, with a significant majority not working or having to reduce their workload during this treatment time. Although there were no significant differences between the two treatment arms, there was a trend towards higher care costs in the DHAP arm. I have a couple comments/questions:

1. A high proportion of patients were already not working at the start of salvage chemotherapy (69% in the GDP arm and 73% in the DHAP arm). Is this because patients were too debilitated from their R/R disease to work prior to even starting chemo? Or were they already not working prior to their R/R disease due to toxicity from their initial disease/treatment or other reasons? Only 3.5% and 7.5% decreased their workload during the chemotherapy. Thus, is it possible that some of the indirect costs are related to disease burden rather than the treatment itself? I’m not sure if this distinction can be made, but I suggest adding your interpretation to the discussion/limitations.

2. Of the ~30% who were working at the start of salvage chemotherapy, what was the proportion working full-time vs. part-time? (The denominator of patients in this statement is unclear: "of those still working full time at baseline, 3.5% reported decreasing their workload (part-time or stopped working) in the GDP arm, compared with 7.4% in the DHAP arm")

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 2 Report

This manuscript is for the most part well-written and clear. My comments relate to some small issues of lack-of-clarity / inappropriate language use.

1. The language around "paid and unpaid caregiving costs generally appeared higher" needs to be toned down. There is (a) nothing to indicate the analysis was powered to detect a change in this outcome, (b) a non-significant p-value found, (c) no presentation of data to help ascertain this isn't caused by a few outliers, and (d) a multiplicity problem (you've tested six hypotheses - many statisticians would argue you therefore need to compare to 0.05/6 to assess significance).

2. What does "WPAI-adapted" refer to exactly?

3. Don't use "average" when you are specifically referring to the "mean". C.f., Abstract and Results.

4. Presenting other summary measures of the data (e.g., median, range, IQR) would be helpful for the reader - the mean alone could easily not tell the full story.

5. How exactly have the authors accounted for the differing number of LP instruments completed by patients?

6. I would not use the word "significant" if you are not referring to statistical significance. C.f., the Discussion, where this is done several times.

7. Why are some of the p-values listed as "NS"? The two given p-values are not-significant, so why are they included and the others not?

Author Response

Please see attachment.

Author Response File: Author Response.docx