Long-Term Follow-Up Cares and Check Initiative: A Program to Advance Long-Term Follow-Up in Newborns Identified with a Disease through Newborn Screening

Round 1

Reviewer 1 Report

This is a well-presented paper on a very important topic of NBS, long term follow-up. If this system works and involves many sites with high coverage of valid data, this will indeed be a great way of collecting critical information on NBS for SMA (and later for more diseases). Also, comparing long term outcome data in early identified children with four (or more) SMN2 copies with and without pre-symptomatic treatment will also be an important question that may be answered.

Some minor thoughts and comments below.

Can the title be changed to avoid abbreviations?

What is the difference between this follow up system and registries? Are there any differences?

Line 53 whose?

Any legal issues in setting this national system up?

In figure 2; how will cognitive function be measured? Any standardized testing tools that will be used? In the box other outcomes, do you mean for example validated patient reported outcome measures (PROMS) and or patient reported experienced measures (PREMS)?

Line 214; why not longer than five years?

One very important thing is also to follow up cases with SMA not picked up by present screening algorithm. If understood correctly (line 220) this will not be done or?

Line 244; From September 2022?

Perhaps not the scope of this article but, do all sites (states) have the same possibility for treatment without symptoms in all genetically defined types of SMA (that is SMN2 copy number)?

Author Response

Thank you for taking the time to provide feedback. We greatly appreciate it! Please let me know if I have thoroughly addressed all suggestions. Thanks again.

1. Can the title be changed to avoid abbreviations?
   1. Done
2. What is the difference between this follow up system and registries? Are there any differences?
   1. LTFU Cares and Check is designed to be a model program for clinicians and state newborn screening programs to work collaborate in the the longitudinal follow-up of newborns identified with a condition through newborn screening. Health information about each newborn comes from the clinicians who care for the newborn and is shared in aggregate format with the state newborn screening program if they are interested in receiving it. It is a registry of sorts but the intent is to build data collection and sharing tools for individual programs to customize and implement.
3. Line 53 whose?
   1. Updated based on recommendation.
4. Any legal issues in setting this national system up?
   1. LTFU Cares and Check is not a national system although this experience could inform national efforts. There are expected to be ethical, legal, and social (ELSI) considerations in setting up a national system.
5. In figure 2; how will cognitive function be measured? Any standardized testing tools that will be used? In the box other outcomes, do you mean for example validated patient reported outcome measures (PROMS) and or patient reported experienced measures (PREMS)?
   1. Added information to include. Since it is based on the clinical site, the language added is as follows: All measurements related to outcomes were reported by the clinicians based on their individual practice.
6. Line 214; why not longer than five years?
   1. It was not longer than five years since newborn screening implementation for SMA began in July of 2018. We expected that the majority of cases would be under five years of life. The text was updated to include this information along with a citation.
7. One very important thing is also to follow up cases with SMA not picked up by present screening algorithm. If understood correctly (line 220) this will not be done or?
   1. This is correct.
8. Line 244; From September 2022?
   1. Updated based on recommendation.
9. Perhaps not the scope of this article but, do all sites (states) have the same possibility for treatment without symptoms in all genetically defined types of SMA (that is SMN2 copy number)?
   1. This is outside of the scope of this article and we did not gather information about state coverage of SMA treatment in presymptomatic cases identified through newborn screening.

Author Response File: Author Response.pdf

Reviewer 2 Report

The authors of the manuscript entitled “LTFU-Cares and LTFU-Check Initiative: A Program to Advance Long-Term Follow-Up in Newborns Identified with a Disease Through Newborn Screening” have embarked on one of the most important and relevant issues nowadays in NBS programs: monitoring long term follow-up after referral. LTFU and sharing data and best practices is of utmost importance for the improvement of clinical care for patients and families. I applaud the authors for their tremendous efforts with this manuscript. The LTFU-Cares and LTFU-Check is based on a well-thought-out design that takes the perspective of patients, families and clinicians into account. I look forward to the implementation of the SMA dashboards as wells as to the initiation of more LTFU initiatives for other conditions in the NBS programs.

Could the authors elaborate on the following:

-        Do parents of patients provide consent for their data to entered into the LTFU Cares and Check Initiative? The information on family income/medical coverage seems quit personal to post on a dashboard.

-          The examples of data dashboards you are presenting in Figure 3 and 4 are visually very appealing. Who would have access to these dashboard? Just clinical sites and state NBS programs or would these dashboards and the data also be available for other countries/NBS program/the public?

-          What would the authors recommend to other NBS programs when starting up similar initiatives? In retrospect, are there any steps that you would have done differently?

Minor comments

-          Line 53-58. Very long sentence, consider splitting

-          Reference 3. Would include scientific publication on benefits of early treatment in SMA patients

-          Introduction: would include additional reference on NBS for SMA and early treatment in addition to Lee et al. It is refered to six times in the text.

Author Response

Thank you for taking the time to provide feedback. We greatly appreciate it! Please let me know if I have thoroughly addressed all suggestions. Thank you again.

•         Do parents of patients provide consent for their data to entered into the LTFU Cares and Check Initiative? The information on family income/medical coverage seems quit personal to post on a dashboard.
•  All of the clinical sites reviewed the project with their Institutional Review Boards (IRB) and received exemption from IRB review and therefore parental consent was not required.

-          The examples of data dashboards you are presenting in Figure 3 and 4 are visually very appealing. Who would have access to these dashboard? Just clinical sites and state NBS programs or would these dashboards and the data also be available for other countries/NBS program/the public?

• Only clinical sites and state NBS programs will have access to site-specific data. The data will not be shared outside of the clinical site and state NBS program.

• - What would the authors recommend to other NBS programs when starting up similar initiatives? In retrospect, are there any steps that you would have done differently?
  • Gathering input from all stakeholders is important to identify the disease-specific and general data points that are most helpful to facilitate care coordination, inform evidence-based treatment, enable continuous quality improvement, and contribute to new knowledge discovery. If the project had additional time, gathering more input on a minimal data set would have been helpful

Do you have any recommendations? See above

Minor comments

-          Line 53-58. Very long sentence, consider splitting Done

• Updated based on recommendation.

-          Reference 3. Would include scientific publication on benefits of early treatment in SMA patients

• Updated to include reference on early treatment

•          Introduction: would include additional reference on NBS for SMA and early treatment in addition to Lee et al. It is referred to six times in the text.
  • • We updated to include additional text.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments for author File: Comments.pdf

Author Response

Thank you for providing your feedback. Please see attachment.

Author Response File: Author Response.pdf