Power Analysis for Human Melatonin Suppression Experiments
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe study is potentially valuable for designing future studies focusing on circadian response and related outcomes. I have two comments regarding the methodology of the study:
1) The study is based on a sample of 41 individuals in a previous study (ref 22). How representative is this sample? What implications does this have for the utility of the study?
2) To test the representativeness of the model/framework generated by the study, the authors used the same sample of 41 individuals. Shouldn't this be tested in a different sample?
Author Response
The study is potentially valuable for designing future studies focusing on circadian response and related outcomes. I have two comments regarding the methodology of the study:
We thank the reviewer for their evaluation.
[R1.1] The study is based on a sample of 41 individuals in a previous study (ref 22). How representative is this sample? What implications does this have for the utility of the study?
The study on which we base the statistical modeling is based on a sample of young healthy adults, aged 18–30 years (mean ± SD; age of 20.8 ± 2.6 y). The empirical sample had the following characteristics (Phillips et al., 2014, https://doi.org/10.1073/pnas.1901824116):
A total of 61 participants were enrolled, of whom 3 were excluded based on actigraphy, and 2 did not complete the study beyond the baseline DLMO. Overall, 56 healthy young Caucasian adults (29 women, 27 men; 20.8 ± 2.6 y of age) completed the study. Participants were free from any medical or psychological conditions, had a BMI of 18–30 kg/m2, and were not taking any medications at the time of the study. Participants had not recently traveled across time zones (1 mo per time zone, up to 3 mo) or engaged in shiftwork in the previous 12 mo. Women were naturally cycling (i.e., free from hormonal contraception) and had a regular menstrual cycle of 21–36 d in duration. Participants were healthy sleepers, reporting no subjective problems or previous diagnoses, and having a regular bedtime before 1 AM. A score of 10 or greater on the Epworth Sleepiness Scale was exclusionary, and participants were predominantly intermediate chronotypes (MEQ score of 52.7 ± 9.2). Participants had an average bedtime and waketime of 23:04 (SD = 44 min) and 07:04 (SD = 44 min), respectively. DLMO occurred on average at 21:05 (SD = 70 min), 2.22 h before bedtime. A total of nine participants wore prescription glasses at each test session.
At present, this study is the largest published study investigating dose-response curves. We believe that more data of this type are needed, and believe that our framework can be applied to future studies. We have added this to the discussion.
[R1.2] To test the representativeness of the model/framework generated by the study, the authors used the same sample of 41 individuals. Shouldn't this be tested in a different sample?
We believe that the approach can be validated in future studies using similar dose-response measurements as in the original study. We have added this to the discussion.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript by Spitschan and coworkers present a novel framework for virtual laboratory based on melatonin suppression experiments, incorporating a Bayesian statistical model. It is an interesting model. However, I have some concerns:
Authors must to include the discussion section.
Please, correct organization of the article (there is a mix of images with the bibliography).
Please provide recommendation for future studies in the discussion section (which does not exist in the manuscript).
Authors should add more critical evaluation of the literature, and an impartial opinion of the pros and cons of Bayesian statistical melatonin model.
Comments on the Quality of English LanguageNo comments
Author Response
The manuscript by Spitschan and coworkers present a novel framework for virtual laboratory based on melatonin suppression experiments, incorporating a Bayesian statistical model. It is an interesting model. However, I have some concerns:
Authors must to include the discussion section.
We have now added a discussion section, discussing limitations, an evaluation and future directions for this work.
Please, correct organization of the article (there is a mix of images with the bibliography).
We thank you for the comment, and have addressed these issues.
Please provide recommendation for future studies in the discussion section (which does not exist in the manuscript).
We have added a “Future Directions” section in the manuscript.
Authors should add more critical evaluation of the literature, and an impartial opinion of the pros and cons of Bayesian statistical melatonin model.
We have now implemented this in the discussion section.
Reviewer 3 Report
Comments and Suggestions for AuthorsSome recommendations or questions to the authors:
1. In your paper, you used the photopic illuminance as “input parameter”, why did you not use the new mEDI-metric or CS2021 (see scientific report’s article of M. Rea)?
2. In the article reference Nr. 22 with Philips A.J. et al., the authors used 55 participants, why did you calculate with n=41?
3. Pls. extend the very short section 3 “conclusion” and formulate in the outlook the aims, how you with the new calculation model and power analysis help to evaluate the other data sets on melatonin suppression of other research groups in the last 23-25 years (e.g. Cajochen, Nowozin, Nagare, M. Rea, Figuiero, etc…).
4. The reviewer sends the text file with some marks back for correction.
Comments for author File: Comments.pdf
Author Response
In your paper, you used the photopic illuminance as “input parameter”, why did you not use the new mEDI-metric or CS2021 (see scientific report’s article of M. Rea)?
We have followed the parametrization from Phillips et al. (2019), which expressed light intensity as photopic illuminance. We have now expanded the discussion to include the point that melanopic EDI should instead be used, and discuss how the findings are nonetheless relevant, as for level-invariant spectra, the melanopic EDI can be related to photopic illuminance by a scalar, which we now discuss in the Results section.
In the article reference Nr. 22 with Philips A.J. et al., the authors used 55 participants, why did you calculate with n=41?
Only 41 participants were included for which reliable model fits could be found by the original authors. We have now included a statement on this.
Pls. extend the very short section 3 “conclusion” and formulate in the outlook the aims, how you with the new calculation model and power analysis help to evaluate the other data sets on melatonin suppression of other research groups in the last 23-25 years (e.g. Cajochen, Nowozin, Nagare, M. Rea, Figuiero, etc…).
We have now included a “Future directions” section in the section.
The reviewer sends the text file with some marks back for correction.
We thank the reviewer for their in-text corrections.
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsI appreciate the authors explanation about the study sample. The information about study participant characteristics, although published before, should be briefly mentioned in this article. Also the limitation and future direction sections need to include a section discussing the implication of the relatively homogenous sample used for developing the model - will this lead to an overestimate of power if the researchers are to study a more heterogeneous sample?
Author Response
We have now addressed the reviewers points in the Limitations section:
The data set was collected in a relatively homogeneous group of participants. Indeed, given the large variability in even this rather homogeneous sample, it is unlikely that more heterogeneous samples would lead to less variable results. Future work should consider including data from diverse populations.
We have also added the sample characteristics in a novel methods subsection.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe authors have answered all my concerns and the manuscript has improved
Author Response
We thank the reviewer for their review.