PONE-D-22-17767Lessons from 20 years of medical cannabis use in CanadaPLOS ONE

Dear Dr. Grootendorst,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We urge you to pay particular attention to the concerns of reviewer 2 regarding the data handling, transparency, and accessibility. Further, reviewer 1 notes that the manuscript needs to be revised to be more accessible to a non-Canadian (international) audience. Overall, both reviewers raise a number of substantive concerns.

Please submit your revised manuscript by Nov 24 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Julian Aherne

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Additional Editor Comments (if provided):

I have received comments from two reviewers, they waiver between major revisions and reject but note that it is a “potentially interesting and useful paper”. I have recommended major revisions under the assumption that a revised manuscript can adequately address all reviewers’ concerns. I urge the authors to pay particular attention to the concerns of reviewer 2 regarding the data handling, transparency, and accessibility. Further, reviewer 1 notes that the manuscript needs to be revised to be more accessible to a non-Canadian (international) audience. Please provide a point-by-point response to each reviewers comment and indicate how the manuscript has been revised.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: N/A

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is a potentially interesting and useful paper on the evolution of Canada’s medical cannabis system during the past two decades. The paper points to an interesting story about the interplay of changes in policy at the federal and provincial levels and how those change were reflected in amount of cannabis produced and consumed, the nature of cannabis products, and price of cannabis. The paper would be improved by some edits to help make the paper more accessible to a non-Canadian audience and more clearly describing variation and changes provincial policies. Below are specific suggestions.

1. Not being Canadian, I was unsure what Health Canada and physician Colleges are. The authors should make edits in the Abstract and throughout the paper to make the paper more accessible to a non-Canadian audience. I believe that physician Colleges set province-specific guidelines for medical cannabis, but that is not clearly stated anywhere in the paper.

2. The interplay between provincial and federal regulations could perhaps be discussed more clearly. Pre-2014, it seems there was a huge difference across provinces in authorizations for medical cannabis (lots more medical cannabis authorized in BC), but this changed in 2014 when a system of commercial growers was created. After 2014, it looks like the size of the medical cannabis market was relatively small in BC. I don’t think this dramatic shift is clearly explained in the paper. Maybe there is no easy explanation. There is a story here about variation in policies, regulations, and maybe enforcement of regulations across provinces and how those things evolved across years.

3. The section spanning pages 4 through 6 could be more succinct and would perhaps be helped by a figure showing a policy-change timeline. Ideally, you might have separate timelines for each province as well, although I am not sure that information on changes in province-level policies across years is available to the authors. (They do have information on provincial variation in restrictions in 2016.)

4. The issue of variation in enforcement of cannabis laws might be worth addressing more explicitly. In the US, one aspect of liberalization of cannabis policy is decriminalization, involving reduced priority given to enforcement of cannabis laws as well as reduction in penalties for violation of cannabis laws. I was unable to figure out how much of this is an issue in Canada’s cannabis laws. One guess I have about what happened in BC is that after cannabis growing by those authorized for medical cannabis was banned, very little effort was put into enforcing that ban and people continued to supply themselves by growing their own cannabis (or having a friend who grew their own) rather than switching to authorized commercial growers. There was probably a lot of diversion occurring in BC, although from Figure 8 it does not look like population-wide prevalence of daily or near daily use was much higher in BC than most other provinces.

5. There were some numbers that were surprising to me about the average number of grams per day per medical cannabis user. In dry form, a gram of cannabis is about 3 joints. Someone who uses daily and heavily might use 1 to 2 grams per day. I was surprised to see 18 grams per day allowed under MNAR in 2013 (page 5) or the average daily dose of cannabis authorized by Health Canada of 5.6 grams (page 10). Even 2 grams per day prescribed by physicians under MMPR (page 11) seems awfully high. Am I misunderstanding something?

6. The authors put information on variation in medical cannabis restrictions by province in 2016 in an online supplement. I would like to see this table included in the body of the paper.

7. In examining national survey data on cannabis use, the authors focus on daily or near daily use. What was the cutoff for daily use? A common cutoff is 20+ days of use in the past 30. Is that what was used here?

8. The authors provide information on price and potency separately for dry cannabis and oils. The authors should briefly clarify how these are linked to different routes of administration (e.g., smoking, vaping, dabbing, and edibles).

9. Does Figure 4 correct for inflation?

Reviewer #2: Uploaded letter, attached.

The authors provide an extensive descriptive history of the Canadian medical cannabis regime by collating data from a wide variety of sources to provide an integrated overview of how the sector has evolved since inception. An extensive amount of data is processed to provide statistical snapshots of several dimensions of the Canadian medical cannabis system over time, including after legalization. The analysis I believe is mostly novel, the manuscript is well-written if not always technically clear, and there are no statistical errors that I can identify.

Unfortunately I can only recommend that PLOS reject the manuscript. The data handling, transparency, and accessibility clearly do not meet the standards of PLOS. This could be potentially fixed, which makes a case for major revisions, but my reading of the manuscript and the authors’ declarations suggests they will be unable to meet the PLOS data standards and hence I recommend rejection. I lay out a number of crucial issues leading to this recommendation below.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachments

Attachment

Submitted filename: plos_one_review.pdf

PONE-D-22-17767R1Lessons from 20 years of medical cannabis use in CanadaPLOS ONE

Dear Dr. Grootendorst,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please ensure that the revised manuscript, including the abstract, is accessible to an international audience; provide clarification regarding the number of grams authorized; and give the manuscript a thorough edit to increase clarity, e.g., ensure manuscript is written entirely in the past tense.

Please submit your revised manuscript by Mar 24 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Julian Aherne

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Based on the comments from one reviewer, the manuscript requires minor revisions: please ensure that the paper, including the abstract, is accessible to an international audience; provide clarification regarding the number of grams authorized; and

lastly the manuscript requires a thorough edit to increase clarity, e.g., ensure manuscript is written entirely in the past tense. I look forward to your revised submission.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The revised manuscript includes additional information requested by the other reviewer and me. The authors’ responses to our question and suggestions were thoughtful. I continue to think the information on the evolution of medical cannabis is Canada presented in the manuscript will be useful to the field. The authors do not run statistical models assessing statistical significance of associations or estimating magnitude of “effects” of policy changes. I think that is fine, although there are place in the paper where the authors should make edits to be more cautious about causal inferences.

The other reviewer raised concerns about data sharing and transparency. My understanding is that almost all the data used by the authors is already publicly available. Where they have put effort into interpreting or coding that data—e.g., rating restrictiveness of province policies—they provide information on their process for doing so. I am not entirely clear on all the rules for data sharing in PLOS ONE publications, but it seems like the authors are in accord with the spirit of transparency.

I had requested the authors make sure their paper was accessible to an international audience. The authors added some clarification on how the system of physician Colleges works in setting province-specific policies into the main body of the paper. It would help readers if the Abstract was written in a way that made it clear what Health Canada and physician Colleges are.

Both the other reviewer and I reacted to information reported on average daily doses of cannabis. The response letter provided some reasons why the average authorized dose under MMAR would have been so high. My takeaway from the authors response is that the number of grams authorized under MMAR, the average number of grams supplied under MMPR, and the actual number of grams per day consumed by medical cannabis users are very different things. It would help the reader if the authors added some clarifying information to the text of the manuscript. If they don’t, many readers, thinking in terms of actual grams consumed, are going to think that the high numbers are due to typographical or data coding errors.

In general, the writing quality of the paper is fine in terms of clarity. That said, this paper presents a lot of information and, if you are not Canadian, a lot of that information is new and confusing. The content of the paper also does not neatly fit into the conventional format of journal article. For example, should history of medical cannabis policy be in the Results section of the Abstract? The structure of the Abstract and the body of the manuscript do not match. The paper could be published in close to its current form, but I believe the authors would be much happier with their paper, and it would receive a much wider audience, if it received a thorough edit to increase clarity, eliminate some typographical and grammatical errors, increase precision of word choice, and, in general, make the paper more reader friendly. One recommendation I have is that the paper be written almost entirely in the past tense. There are several places where the authors slip into the present tense, which tends to impart stronger inferences than the past tense. The strength of inferences is general issue with this paper. The manuscript is primarily descriptive. I would caution against make statement that imply specific policy changes “caused…”

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Lessons from 20 years of medical cannabis use in Canada

PONE-D-22-17767R2

Dear Dr. Grootendorst,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Julian Aherne

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The revised manuscript addresses the concerns of the reviewers. I recommend that it is accepted for publication.

Reviewers' comments: