Cost Analysis of a Digital Multimodal Cancer Prehabilitation

Round 1

Reviewer 1 Report

The authors provide a manuscript of relative importance considering the increase in prehabilitation evidence, interest, and implementation. While the core findings of this work have the potential to be very impactful to the field of oncology, considerable effort is needed to revise and clarify many points in the methods and results. Further, there is a need to temper some of the conclusions that are made by the author team in the discussion section that extend beyond the findings from the analyses conducted. The methodology of assessing direct costs next to QOL and utility measures is quite novel and can go quite a way to substantiating the implementation of prehabilitation programs.

General comments:

-          Please be concise in describing the prehabilitation program. In some areas of the manuscript it is called “prehab”, in some it is called “pre-rehabilitation”.

Revision and clarification points

Introduction

-          The first paragraph of the introduction should be tempered regarding the described benefits of prehabilitation and needs additional citations to substantiate statements. “The period between a patient being diagnosed and staring treatment has been identified as a critical period for the success of any treatments”. This should be tempered, or put into better context regarding the benefits of prehabilitation, and should be referenced. The next sentence, regarding “patients with optimal physical and psychological function…have improved survival rates.” even more so requires citation.

-          Paragraph 2: The last sentence is confusing regarding the effectiveness of ‘unimodal interventions” it is unclear what these interventions “did not make a difference” in?

-          Paragraph 3, sentence “This study aims to explore” seems to be grammatically backwards? The study aims to explore the impact of a digital prehabilitation program on HRQOL and inpatient costs.

Methods

The entire methods section is difficult to follow. A suggestion would be to use sub-headings to help the reader follow the methods in a logical flow all of the information is in the methods section, but it seems to jump between topics of QOL and cost, without concise format for the reader to follow. Sub section suggestions:

Digital Intervention – describe the digital intervention in greater detail. It is completely unclear as to whether this is a self-guided program, a clinician or provider guided program, individualized or group?, is it an app that just provides recommendations? Is there a specific interface? How are topics/sessions structured? While citing previous publication is fine, there should be some further context provided about the digital intervention.

Measures- describe the QOL and cost measures and how data were obtained

Analysis – describe the type of analysis conducted to derive the utility score and the cost outcomes.

Additional methods considerations:

-          The first paragraph of the methods section seems to portray results, you describe the types of cancer diagnoses of patient involved in the program and the types of treatments they received. This is better suited to the results section and could be enhanced to breakdown how many patients were in each of these groups: colorectal cancer (n=X), lung (n=X) single therapy (n=x)  combination therapy (n=X) perhaps this is a demographic table of participants?

-          Please define that the “inpatient care” you are referring to is the hospital stay associated with the patients cancer surgery. Stating “the cost of prehab services and inpatient care were calculated…” is confusing and might make a reader unfamiliar with prehabilitation believe that this care is delivered inpatient!

Results:

-          Why were only costs for colorectal and urological patients broken out in Table 4? It would help to have the number of patients associated with each of these diagnoses.

Discussion

Please clarify: “Our study showed that even a single prehab session improved QOL…” there is no where that this is broken out in the results section. Your categorical groups start with 0-2.99 weeks of prehab, you do not quantify number of visits anywhere in the results so this statement should not be made in the discussion section.

Please clarify: “Patients having non-surgical oncology management…” it should somehow be identified in the methods section that there is a group that was continuously managed through ‘prehab’ because they were not managed surgically. Do you define prehab as ‘the time before surgery’ or ‘the time before treatment initiation?”. If the latter, then there is greater need for clarity in the description of the population(s) being studied.

The paragraph on the strengths of the study has many overstatements that should be tempered. 1. This study did not assess the “right dose” of cancer prehabilitation. You did assess variability in dose, but there is no comparison to suggest the ‘right dose’. 2. The digital mode of delivery does not “remove any barriers to service access.” Digital can reduce barriers, but may in fact introduce barriers for individuals who to not have adequate data plans, equipment/hardware, or tech savvy to participate. (you can ref Gorzelitz et al. 2022- which identified the many barriers to providing digital exercise). 3. “the availability of a remote prehab program was not a barrier for older patients but resulted in reduced transport costs and time efficiency.” Your study does not quantify the age of your population, and therefore any reference to ‘older patients’ cannot be substantiated. Further, you are making assumptions about transportation costs and time efficiency.

An additional weakness or limitation should be noted that there was no quantification of the severity of this populations cancer. No identification of disease stage or grade was provided and therefore it is a challenge to assume the direct linear relationship of giving the prehab program and obtaining the positive QOL outcomes.

The statement “Our findings support the digitalization of prehabilitation programs.” is overstated. You did not explore the process of digitalization. Making this assumption should be put in context. Your findings support that a digital prehabilitation program could be an effective mode of intervention for some patients.

Author Response

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Author Response File: Author Response.docx

Reviewer 2 Report

Dear authors,

 

With great interest I read you paper entitled: Cost analysis of a mulitmodel cancer prehabilitation. The study is interesting and well written.

 

While I enjoyed reading the manuscript, I do have major and some minor issues. 

 

Major:

1. you have included a 192 patients with a wide range of cancer types. These cancers by themselves differ in their pathophysiologic responses within the host and the treatment options differ radically between the diverse subtypes. These effects will influence the QOL and QALY's. How did you correct for these differences within your data?

2. It is unclear whether all patients started with prehabilitation and cancer treatment was initiated afterwards. In the discussion, it is mentioned that some cancer treatments ran paralell to the prehabilitation. How does this influence your results?

 

3. Substantial results to judge the scientic soundness of the manuscript are missing:

- What was the composition of the study group? Results are not described.

- how many patients were included per prehabilitation band?

- how many dropouts? How did you handle digitally impaired patients? 

- how was the compliance to the programme?

- how many patients were referred and how many self referred? 

- in what period were patients included?

- not having a control group is mentioned as a weakness of the study. However, inpatient costs can be calculated retrosepctively to make a comparison between prehabilitation and controls. 

 

4 Figure 1 and 2 state that during follow up the utility score and Qol scores increase during time. The explanation on how that is possible is missing in the discussion.

- Do all bands of prehabilitation compose the group between baseline and post-rehab? How do you statistically correct for the difference between these patients at the following time points? 

- How do you explain that only at the 6 months checkpoint there is a difference between the different bands? Please discuss. 

 

 

Minor issues:

- is ref 11 correct? This ref is not sufficient to calculate the inpatient costs of all patient groups. 

- please elaborate on the prehabilitation program in your M&M and then refer to the literature. Readers don't like to be referred to another paper in order to understand the current one. 

- the fisrt two sentences of the conclusion should be removed as they do not strengthen the conclusion

 

 

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

In this study the authors present their results of a digitally-based prehabilitation programme for cancer patients. Although the study includes some interesting results (particularly the estimation of QALYs with prehabilitation), I think the paper has several flaws, specifically regarding its main objective (cost-analysis of the service). To be honest, I don't understand what is the purpose of the investigation as no cost-effectiveness analysis has been done and only the costs associated with the program and the treatments are reported. So, I am having a difficult time in understanding how this impacts prehabilitation and its implementation in clinical practice. Therefore, although I think the results on HRQoL and estimated QALYs are interesting, the cost analysis in my opinion offers little to no added value. In addition to this, there are several aspects of the manuscript that need revision:

 

Introduction:

I feel the introduction should be improved, as the focus of the research paper is lost somehow between reviewing defining prehabilitation and describing its benefits. I feel like if the paper is a cost-analysis of the effectiveness of telerehabilitation a stronger background should be provided related to the evidence on the topic. Indeed, the first metion of digital health programmes is almost at the end of the introduction, and I feel should be incorporated before. Also, there is evidence on the cost-effectiveness of prehabilitation in controlled (see Barberan A et al. BJA 2019, Boden I et al. J Physiother 2020) and uncontrolled (Risco R et al. Ann Surg 2022). I feel some of these should be included in the introduction. Another thing is that surivval is mentioned here ("we do not have studies looking into the long-term survival rates") but no assessment of survival rates have been done. I don't see the point of including this sentence as rationale for conducting the study. The last point regarding introduction is that authors focused on uro-oncologic as example for the efficacy of prehabilitation but the study population includes several cancer types (I just don't understand why the use of uro-oncology here as there is actually one of the less studied cancer types in prehab). 

 

Methods

-Could you provide details of patients' retainment throughout prehabilitation? It is mentioned that some patients have 5 assessments while others have only 1. Can we know retention and dropout rates? I feel this is important for cost-effectiveness of an intervention. 

-Just as curiosity, what kind of patients were in bands 3 and 4 of prehab? It seems too long waiting for 10 weeks for a cancer treatment. 

-Is there any reason why inpatient costs were calculated from the literature? Could you perhaps elaborate why was not possible to assess direct inpatient costs associated from treatment? (i.e: surgery). It should be feasible considering the sample size of the study. 

 

Results:

-If I understand correctly, between post-prehabilitation and 6-weeks post-prehabilitation, a course of treatment for cancer occurred, is that correct? I assume, there should be an immediate decrease in health-related quality of life in response to treatment, but that is not noted in the study. Could you please comment on that?

-I feel a little confused about the use of the terms prehabilitation/rehabilitation. Does this mean that the average patient received rehabilitation services during and after cancer treatment? If that is the case, I don't think we can talk here about prehabilitation, as the intervention is (as defined in the introduction) between diagnosis and the initiation of treatments. That'll have large implications in the cost-analysis. Could you please clarify that?

 

Discussion

-The summary provided in the first two lines of the discussion does not seem to align to the initial objectives of the study. What dose-respond effect are we assessing here? It is obvious that the longer a patient is using a given treatment, the greater the costs associated are. In addition, the results are not really reporting onthe cost-effectiveness of the intervention as the potential savings are not calculated; therefore, you are only displaying the costs of the prehab service in addition to the inpatient costs. These do not reflect the objective of the study. 

 

Minor commnents:

-I feel the fourth line in the results section is a little confusing, I think it needs rephrasing. 

-In table 2 there's a typo in the first colum (it says 0-32.99 weeks instead of 2.99)

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

This manuscript is tremendously improved. The authors attention to reviewer comments and restructure of the methods section as well as the addition of descriptive population data improve the quality of this manuscript and the readability. 

Author Response

Thank you so much for your kind comments.  We appreciate the time and effort that you have dedicated to providing feedback on our manuscript and are grateful for the insightful comments on and valuable improvements to our manuscript.

Reviewer 3 Report

Thank you for the authors for providing the revised version of the manuscript. I think the paper has improved and now objectives are clearer. However, I still have some issues regarding some aspects of the manuscript.

- What is the rationale for calculating inpatient costs in those undergoing prehabilitation if no comparison is done with those patient not referred to prehab? It seems like inpatients costs are only important in the context of this particular piece of research if they're compared agains those not doing prehabilitation or maybe even compared to those undergoing face-to-face traditional prehabilitation. This way, you could have a clearer idea of whether the additional costs of the programme are compensated by decreases in inpatient care.  I noted that you included the lack of a control group in the limitations of the study, and I understand this is not an analysis you can performed now; I am merely suggesting that in my opinion if the objetive of the study it's just to report on the costs of a digitally-based prehab programme, I don't see the benefit of adding inpatients costs here.

-Thank you for clarifying the distinction between surgical and non-surgical patients and how prehabilitation was offered in both, although I do have to say that I am not sure I agree we can refer to prehabilitation in the latter case, more cancer rehabilitation in general. In either case, be consistent with the term used. Prehabilitation is used throughout the manuscript, but in the results sections and in the tables rehabilitation is used instead. 

-T2 was post-prehabilitation; could you specify at which point was this measured? Was it only for surgical patients before surgery? T3-T5 all say post-prehabilitation, measured from baseline. That this means that this endpoints were performed 6 weeks and 3 and 6 months before staring prehabilitation? For those patient undergoing chemoradiotherapy, the length of the treatment course is longer meaning the could still be receiving prehabilitation services, is that correct? I feel the term post-prehabilitation is misleading here. 

-How was adherence to a digitally-based intervention measured?

-Could you please add maybe in the discussion section, an overall interpretation of the study findings? I feel like the increment in QALYs is difficult to interpret with the raw data, without including any reference for similar interventions. I mean, is it an increase in QALYs of 0.6 relevant for the cancer patient? (I assume it is but it would be useful to see this discussed in the paper). 

-As a minor comment, I would say that the sentence that says "prehab services are a great way for patients to spend their time" is not appropriate, as It seems that patients are "entertained" during their pre-treatment phase instead of prehabilitation having a real, tangible purpose of improving patients' fitness. 

Author Response

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Author Response File: Author Response.docx