Study Protocol: Psychometric Testing of the German Vestibular Schwannoma Quality of Life Index—A Multicenter Study on Quality of Life and Patient-Centered Care in Vestibular Schwannoma

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors Thank you for an imperative topic on patients' quality of life!
It would be nice, though, to attach the actual questionnaire that will be given to patients. Even if it is in German.

Author Response

 

We thank the reviewer for the positive feedback and for highlighting the relevance of the topic.

It would be nice, though, to attach the actual questionnaire that will be given to patients. Even if it is in German.

 

Response:

Thank you for this valuable suggestion. We agree that including the questionnaire enhances the transparency and comprehensibility of the study protocol. Accordingly, we have attached the German version of the questionnaire as a supplementary appendix to the revised manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review the submitted protocol entitled: “Psychometric Testing of the German Vestibular Schwannoma Quality of Life Index - A Multicenter Study on Quality of Life and Patient-Centered Care in Vestibular Schwannoma.”

This protocol aims to validate the German version of the VSQOL among patients with vestibular schwannoma. Although the tool has already been translated by the same research group, its psychometric properties have not yet been fully evaluated. Therefore, this study addresses an important gap and is expected to contribute meaningfully to improving patient-centered outcomes in this population.

Overall, the study tackles a clinically relevant and timely topic. The authors plan to use established and validated instruments for comparison, which strengthens the methodological rigor. The multicenter cross-sectional design is appropriate for psychometric validation, and the inclusion and exclusion criteria are clearly defined and suitable for the study objectives.

However, I have a few minor comments:

• The sampling strategy relies on convenience sampling, which may introduce selection bias and should be acknowledged as a limitation.
• The statistical analysis plan is generally appropriate; however, I recommend that it be reviewed by a statistician to ensure optimal methodological robustness, particularly for advanced psychometric analyses (e.g., CFA and handling of missing data).

Overall, this is a well-designed and potentially impactful study. With minor methodological clarifications, it can provide valuable insights into QoL assessment and patient-centered care in vestibular schwannoma patients.

 

Author Response

We sincerely thank the reviewer for the thoughtful and encouraging assessment of our study protocol.

 

The sampling strategy relies on convenience sampling, which may introduce selection bias and should be acknowledged as a limitation.

 

Thank you for this important comment. We fully agree that the use of convenience sampling may introduce selection bias and potentially limit the representativeness of the study population. We have therefore explicitly acknowledged this as a methodological limitation in the Discussion section of the revised manuscript: „First, the sampling strategy relies on convenience sampling, which may introduce selection bias and limit the representativeness of the study population.”

“In particular, the inclusion of an online cohort and recruitment via mailing lists from a patient organization may result in a sample that is more proactive, engaged, or health-literate than the general VS population“

 

The statistical analysis plan is generally appropriate; however, I recommend that it be reviewed by a statistician to ensure optimal methodological robustness, particularly for advanced psychometric analyses (e.g., CFA and handling of missing data).

 

We appreciate this helpful recommendation. In response, we have clarified in the revised manuscript that the statistical analysis plan will be reviewed in consultation with a statistician to ensure methodological robustness, particularly regarding advanced psychometric analyses such as confirmatory factor analysis (CFA) and the handling of missing data. In addition, we have now specified that the analysis plan has been developed in close alignment with the authors of the original questionnaire: „Secondly, while the planned statistical analyses are generally appropriate, the complexity of advanced psychometric methods, particularly CFA, poses potential chal-lenges. Specifically, there is a significant risk that CFA models may fail to converge due to small sample sizes, particularly in subgroup analyses (e.g. by recruitment site or online cohort). This could restrict our ability to evaluate measurement invariance across various patient settings, so this should be considered when interpreting subgroup comparisons. To address this issue, we will consider using simplified or partial models, as well as aggregating subgroups where appropriate, to ensure model stability. Addi-tionally, if CFA proves infeasible in certain subgroups, alternative approaches such as exploratory factor analysis (EFA) or item-level analyses may be applied. Importantly, the statistical analysis plan has been developed in close alignment with the authors of the original questionnaire. To enhance methodological robustness, the statistical anal-ysis plan will be reviewed in consultation with a statistician.“.

Reviewer 3 Report

Comments and Suggestions for Authors

This manuscript/study protocol is generally well written and concise. I did not identify any relevant formal or contextual errors. The overall clinical impact will of course depend on the future work. However, assessment of QoL in vestibular schwannoma patients is a unifying area of interest that connects all involved disciplines. I have no concerns regarding its publication. 

Author Response

Thank your for your opinion!

Reviewer 4 Report

Comments and Suggestions for Authors

This study protocol outlines a multicenter, cross-sectional validation study designed to psychometrically test the German version of the Vestibular Schwannoma Quality of Life (VSQOL) Index.

While the protocol is well-structured, the following areas warrant careful consideration:

The authors acknowledge a significant risk regarding the Confirmatory Factor Analysis (CFA) for subgroups. Due to potentially small sample sizes in specific recruitment centers or the online cohort, the complex model may fail to converge. This could limit the ability to assess measurement invariance across different patient settings.

The protocol states that cases with excessive missingness (>70%) may be excluded. While a systematic approach (multiple imputation, FIML) is planned for random missingness, a 70% threshold is quite high; the authors should clarify if such high attrition might introduce systematic bias, especially if patients with worse symptoms are less likely to complete the 40-item index.

The use of an online cohort and mailing lists from a patient organization may result in a sample that is more proactive or health-literate than the general VS population. While the authors plan to conduct descriptive analyses of these subgroups, the potential for selection bias should be highlighted in the future limitations section of the results paper.

The exclusion of patients with Neurofibromatosis 2 (NF2) is justified to maintain the specificity of the VSQOL, as NF2 patients require different assessment tools like the NFTI-QOL. However, this limits the generalizability of the findings to the broader VS patient population, specifically those with genetic predispositions.

The protocol demonstrates a strong commitment to ethical standards, adhering to the Declaration of Helsinki and GDPR. The use of encrypted databases (LimeSurvey and the "Chili" portal at Heidelberg) and a clear anonymization process provides adequate protection for participant data. 

Author Response

We thank the reviewer for the thorough and highly constructive assessment of our protocol.

The authors acknowledge a significant risk regarding the Confirmatory Factor Analysis (CFA) for subgroups...

 

Thank you for highlighting this important methodological aspect. We agree that subgroup-specific CFA models may be at risk of non-convergence due to limited sample sizes in individual recruitment centers or the online cohort. This concern has now been more explicitly discussed in the revised manuscript, including the potential limitation regarding the assessment of measurement invariance across different patient settings.

 

The protocol states that cases with excessive missingness (>70%) may be excluded...

 

We appreciate this important observation. We have revised the Discussion section to explicitly acknowledge that a high threshold for exclusion due to missingness may introduce systematic bias, particularly if patients with more severe symptoms are less likely to complete the full questionnaire. This issue will be carefully considered during the interpretation of the results.

 

The use of an online cohort and mailing lists from a patient organization may result in a sample that is more proactive or health-literate than the general VS population...

 

Thank you for this insightful comment. We fully agree and have now explicitly included this as a potential source of selection bias in the Discussion section. We further state that this limitation will be highlighted in the future results manuscript when interpreting subgroup analyses: „While the study design aims to ensure methodological rigor, several limitations must be acknowledged. Firstly, the sampling strategy relies on convenience sampling, which may introduce selection bias and limit the representativeness of the study population. In particular, including an online cohort and recruiting via mailing lists from a patient organisation may result in a sample that is more proactive, engaged or health literate than the general VS population. Although descriptive subgroup analyses are planned, this potential bias should be considered when interpreting the findings, and it will be addressed further in the 'Limitations' section of the results manuscript.“.

 

The exclusion of patients with Neurofibromatosis 2 (NF2)... limits the generalizability...

 

We thank the reviewer for this important point. We agree that while the exclusion of NF2 patients is necessary to maintain the specificity and validity of the VSQOL instrument, it does limit the generalizability of the findings. This limitation has now been explicitly acknowledged in the revised manuscript.