PONE-D-21-07384

Support Models for Addiction Related Treatment (SMART) for Pregnant Women: Study Protocol of a Cluster Randomized Trial of Two Treatment Models for Opioid Use Disorder in Prenatal Clinics

PLOS ONE

Dear Dr. Forray,

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Academic Editor

PLOS ONE

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"I have read the journals policy and the authors of this manuscript have the following competing interests: Dr. Nancy Byatt has received salary and/or funding support from Massachusetts Department of Mental Health via the Massachusetts Child Psychiatry Access Program for Moms (MCPAP for Moms). She is also the statewide Medical Director of MCPAP for Moms and the Executive Director of Lifeline4Moms. She has served on the Medscape Steering Committee on Clinical Advances in Postpartum Depression. She received honoraria from Medscape, Miller Medical Communications and Mathematica. She has served on the Perinatal Depression Advisory Board for the Janssen Disease Interception Accelerator Program, Advisory Boards for Sage Therapeutics. She has also served as a consultant Ovia Health, Sage Therapeutics or their agents, and has received speaking honoraria from Sage Therapeutics. Dr. Kimberly Yonkers has consulted to Athenen Pharmaceuticals. Dr. Leena Mittal consulted to Sage Therapeutics."

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Partly

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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

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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

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This study presents a protocol for a trial aimed to investigate best practices for supporting OB care teams to integrate OUD treatment into OB care for pregnant women. I am happy to hear this trial is funded and going to take place, as we are desperately in need of evidence-based approaches at the ‘practice’ level to support providers in addressing the overdose crisis, especially for a priority population like pregnant and parenting people. Below I outline some queries and suggestions to strengthen the manuscript.

TEXT

- For the SMART ECHO program, is there a set curriculum that will be carried out across instutitons? Will it be one ‘hub’ for all participating study practices? Or will there be mlultiple?

- For the CC-OP, the registry is broight up in the methods multiple times, coming off as critical to proper data collection as well as effectivesnes of the intervention. Later on in the manuscript it starts to become more clear what this registry is – but would be helpful earlier on. For example, who is in charge of keeping this registry?

- Will there be one case manager per site? Full time positon? What qualifications will the CM have?

- Under primary outcomes, it says ‘treatmnet for opioid misuse’ – to be consistent with methods, I believe this should be OUD

- Will the treatment retention outcome be censored at 3 months? How will you handle that the ‘end of the study’ is 3 months but people may start treatment at different times

- Also, it is imperative that a justification for why this study will stop measuring outcomes at 3 months postpartum, rather than 12 months, is recommended – given that 7-12 months is the highest risk time for postpartum women with OUD for overdose, as an example.

- How will you measure if a patient was ‘offered’ MOUD? By provider doucmentaiton – and then chart abstraction? If yes, how will you mitigate information bias?

- Will substance use recurrence be measured only by urine drug test, or also by self-report? Post COVID, we are doing a lot more telehealth, so how will you take that into consideration for outcome measurement – such as for substance use recurrence?

- Please use person first language throughout. Ex: page 10, ‘users’ and ‘misusers’ is not appropriate, please use terminology more consistent with ‘individuals who use…’

- For the screening outcome, how will a ‘screen’ be measured? By use of a validated tool within context of a patient-provider interview?

- For the ‘contacts’ part under fidelity procedures, is this referring to contacts between providers?

- For the SMART ECHO measures – such as the leveraging of technologu, quality checklist, etc. Have these measures been used by other ECHO studies in other areas of medicine? If yes, references would be great.

- For the sample size descriptions, I don’t see any discussion that these #s will be feasible at the sites? For example, 90 eligible participation per cluster for hypothesis one paragraph is not a small number – will that be feasible? And how do you know that?

- The description of the qualitative methods is lacking – sample size justification, has the interview guide been developed – and based on what, planned analysis, etc. etc.

- Lastly, and very importantly, after reading the whole article it is not clear to me if the purpose of this study is to show which of these 2 models are BETTER at accomplishing the intended outcomes. Or is it rather to show that both are feasible and attain the intended outcomes?

TABLES/FIGURES

Figure 1: Is the NIDA Quick Screen what needs to be done for the screening outcome? How did you choose this one? In other studies, this is not superior to other tools such as 4Ps and SURP when restricted to pregnancy. Also, what is ‘Assigned OUD treatment’? Please delineate in table what are patient and what are provider measures.

Figure 2: In the text it says patients can be enrolled up to 34 weeks, but there is a 26 week questionnaire. What will be done for those who enroll after 26 weeks? Also, add ‘patient’ to title.

Table 1: Would be great if how these outcomes are specifically defined is added to table, or at least in footnotes.

Table 2: Same here, at least for the measures that are not self-explanatory

Reviewer #2: Thank you for the opportunity to review this protocol. The work is important and addresses an area of clear need. My main concern with the paper is the lack of clarity around the comparison and hypothesis. The study is a direct comparison of two models of care using a cluster RCT. There is no comparison to either usual care of gold standard care. The authors appear to hypothesize that the case manager model will be more effective, but this is buried in the paper and is not entirely clear. I think this needs to be explicitly addressed and the hypotheses explicitly stated and restated where necessary.

I have only a small number of comments which I hope will bring better clarity for the reader.

1. SMART is already a commonly used acronym in addiction treatment. SMART-Recovery (Self Management And Recovery Training) is an internationally recognised self-help group and this project could be confused with that (for e.g., its impact on pregnant women). This is a minor point only, but the authors may wish to consider a way of distinguishing the two terms.

2. I found the first paragraph of the introduction difficult to follow and the third sentence “Approximately 7%...use of their medication” unnecessary and should be removed. The key issue to my mind is that, due to the opioid crisis in the US, there has been an increasing number of women with opioid use disorder who are pregnant, but there is paucity of specialist obstetric/addiction providers. The introduction could be more clearly and plainly laid out.

3. Second paragraph under Methods and Design – there is superfluous detail regarding Institutional Review Board approval, for e.g., I do not think the address of the IRB is needed.

4. Minor error paragraph 1, page 6, “buprenorphine-wavered” should be “buprenorphine-waivered”.

5. More detail is required for site recruitment. Presumably the obstetric centres recruited were approached directly by the study team? Can the authors provide a little more detail on how an “obstetric centre” is defined?

6. Individual participants (i.e., eligible women) will have to provided consent, what data if any will be collected on those who do not provide consent?

7. Page 14, it would be beneficial for the authors to restate each of the hypotheses to contextualise the power calculations.

8. How many trial participants are expected to be interviewed in the qualitative arm? A little more detail in this section would be useful.

9. Will there be any health economics data collected?

10. Will social outcomes be measured? For example, how many of the infants are removed by social services? Or what level of social service involvement for each group?

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Reviewer #1: No

Reviewer #2: No

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Support Models for Addiction Related Treatment (SMART) for Pregnant Women: Study Protocol of a Cluster Randomized Trial of Two Treatment Models for Opioid Use Disorder in Prenatal Clinics

PONE-D-21-07384R1

Dear Dr. Forray,

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.

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Kind regards,

Yukiko Washio, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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

**********

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

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you authors for addressing the reviewer comments. The paper is a lot more clear, understandable, and thus will be an even better addition to the literature for a general audience. A couple minor things below to consider before publication:

- As a clinician, it is still not clear to me the role that the case manager will play in the trajectory between screening > assessment by provider for OUD > treatment options presented > treatment initiation. Will the CM be the one to contact the pt if the screen is positive? Or does the provider refer the patient to the CM after discussing a positive screen with the patient? Then the CM coordinates follow up apts for the OUD assessment? etc. ? Thank you for clarifying.

- How long after a patient 'receives' the diagnosis of OUD will the pt be recruited for study participation? It can be challenging, and overwhelming, for patients entering care let alone OUD treatment for the firs time during pregnancy - and then also being approached for a research study can further that. Is there a limit' on how long after OUD dx people remain eligible to participate - the more flexibility the better, likely, to allow for optimal recruitment rates.

- Thank you for adding the information about the specifics of the hypotheses. It is interesting (yet not surprising) that all the hypotheses lean towards the case management arm outperforming the ECHO arm. Yet based on the descriptions of the trial interventions/arms earlier in the paper, I was coming into this section of the manuscript thinking they were likely going to be on par with one another. Potentially adding one sentence to the discussion or elsewhere stating WHY the authors hypothesize that the CM arm will achieve better patient outcomes than the ECHO arm will be useful for context.

-A chunk of the discussion revolves around payment/costs, which is very important. What is in the protocol, data collection wise, to ensure that a proper, robust cost benefit analysis will be able to be performed at the conclusion of this trial?

Reviewer #2: The authors have generally and adequately addressed my queries.

However, consistent with my earlier comment, given the potential confusion with SMART recovery, I suggest the authors reconsider the title by either removing the acronym SMART or add in the word “Project” as a prefix to the acronym. I believe this would benefit the readership and avoid confusion, but the suggestion is at the author's (or the editor) discretion.

Likewise, I appreciate that a health economics component is not part of the trial and I think that is disappointing as any intervention for this group will need to be economically viable for the healthcare system and is therefore an important piece of the effectiveness puzzle. As such, I would encourage the authors to at least consider this point in the discussion. Again, however, how much the authors engage with this should be a the author’s discretion.

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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

Reviewer #2: No