1000 Families Study, a UK multiwave cohort investigating the well-being of families of children with intellectual disabilities: cohort profile

Purpose The 1000 Families Study is a large, UK-based, cohort of families of children with intellectual disability (ID). The main use of the cohort data will be to describe and explore correlates of the well-being of families of children with ID, including parents and siblings, using cross-sectional and (eventually) longitudinal analyses. The present cohort profile intends to describe the achieved cohort. Participants Over 1000 families of UK children with ID aged between 4 and 15 years 11 months (total n=1184) have been recruited. The mean age of the cohort was 9.01 years old. The cohort includes more boys (61.8%) than girls (27.0%; missing 11.1%). Parents reported that 45.5% (n=539) of the children have autism. Most respondents were a female primary caregiver (84.9%), and 78.0% were the biological mother of the cohort child with ID. The largest ethnic group for primary caregivers was White British (78.5%), over half were married and living with their partner (53.3%) and 39.3% were educated to degree level. Findings to date Data were collected on family, parental and child well-being, as well as demographic information. Wave 1 data collection took place between November 2015 and January 2017, primarily through online questionnaires. Telephone interviews were also completed by 644 primary caregivers. Future plans Wave 2 data collection is ongoing and the research team will continue following up these families in subsequent waves, subject to funding availability. Results will be used to inform policy and practice on family and child well-being in families of children with ID. As this cohort profile aims to describe the cohort, future publications will explore relevant research questions and report key findings related to family well-being.

- Table 2 (presented on p. 11) describes the measures used within the study and indicates that they are measured at T1 and T2. Does this mean that these measures were collected during wave 1 and wave 2? -I would like to see a more detailed description of the child with ID. For example, the mean scores (and range) on the Vinelands that were collected and whether the authors collected any information about cognitive assessments that families could report, e.g., based on previous diagnostic assessments.
-In the description of the primary caregiver and family, it would be helpful to know how many siblings were in each family and whether the siblings had any diagnoses, such as ID or ASD. -In the cohort description, I would also like to know whether the authors collected information on other genetic conditions typically associated with ID, aside from autism and Down Syndrome (for example, Fragile X, tuberous sclerosis, Williams Syndrome, Cornelia De Lange etc.). Similarly, did the authors collect any information about medical comorbidities (e.g., epilepsy, cerebral palsy), which may affect family wellbeing over and above the ID on its own? It would be worthwhile to present this information in the description of the cohort.
-The authors have included information about the proportion of families living in the most deprived areas of the UK. It would be helpful to see where the participating families came from across the UK, perhaps using a visual? Findings to Date: -Much of the information in the 'Findings to Date' section belongs with the cohort description, as the authors are referring to the characterisation of the sample. Have there been any key findings or publications related to family wellbeing that have come from this sample? -The families were asked to describe the severity of their child's ID. It would be helpful to know how this was operationalised for the families. Future Directions: -The authors could provide more specific details about the questions that they hope to answer using this cohort and the rationale for future work. Strengths and Limitations: -In my opinion, the way that the comparisons of the characteristics of the families that did and did not take part in the telephone interviews is not very meaningful. Simply stating that one group had a higher mean score than the other, without indicating whether this difference was significant, nor an effect size or confidence intervals, does not tell us very much. I think this section could be reworked and presented more succinctly.

Summary
This manuscript reported on an ongoing cohort study of over 1000 families of children with intellectual disabilities ages 4-15 years. The report describes the methods of the study including detailed listing of measures to be obtained. It further provides descriptive information about the families. Finally, it reports that next stage (Wave 2) data collection is ongoing.
General Comment: I commend the authors for addressing the very important issue of treatment of children with ID as well as the comprehensiveness of the measures to be undertaken. However, the data as presented seems limited in order to make any clear assessment of the value of the study. In Table 1. SES and demographic data on Wave 1 information is presented. In Table 2 Given the large amount of information obtained from the parents, why not simply ask the parent what educational setting the child is attendingas this would provide at least a preliminary correlation with the function of the child.
Comment #5; Page 19, Line 3-31 "Children of caregivers who did not take part in the telephone interview had higher total SDQ scores with a mean score of 18.3 for the children whose primary caregivers did not take part in the telephone interview compared to a mean score of 16.8 for those who did. The child with ID having multiple diagnoses, however, did not decrease the chances that a primary caregiver would complete a telephone interview. For example, those children with ID whose primary caregivers completed a telephone interview were more likely to have a coexisting physical health problem (such as epilepsy, mobility problems, hearing or visual problems). The children whose primary caregivers completed a telephone interview had a mean number of health problems of 1.70 compared to 1.06 for the children with ID whose primary caregivers did not complete a telephone interview. Additionally, the children whose primary caregivers completed a telephone interview were more likely to have a greater number of diagnostic labels, with a mean number of 2.18 compared to 1.45 for the children with ID whose primary caregivers did not complete a telephone interview." From my reading of the manuscript, the above quoted paragraph contains the only information regarding results of measuresand specifically comparing parents who completed the phone interview vs. those that did not. Why is this information not located on page 15 under the heading "FINDINGS TO DATE"?
Clarification of this point is important to allow the reviewer to understand why only this information was presented and not others. More complete statistical data, such as standard deviation, would also be helpful.

VERSION 1 -AUTHOR RESPONSE
Reviewer #1 comments: 1.1 "This paper describes a cohort of 1000 families of children with intellectual disability, that took part in a study of family wellbeing. The cohort has strengths due to its size and includes cross-sectional and longitudinal data. While the study overall is important, this specific manuscript could be tightened to make sure that it is describing the cohort rather than the study as a whole".

RESPONSE
Thank you for your positive comments. We have made edits throughout the manuscript to ensure the focus is on describing the cohort, and to provide further information on the cohort to highlight the strengths outlined. Edits in response to the other reviewers' comments have also helped to achieve this.
1.2 "I think that the information in the 'Participants' and 'Findings to date' subsections of the abstract should be switched. Currently, the findings to date section includes a characterization of the sample, and the participants section contains information about the data that has been collected. I think that this should be reversed."

RESPONSE
This order of information has been reversed as suggested ('Abstract', p. 2).
1.3 "The strengths and limitations section makes reference to the 'study' in addition to the 'cohort'. Given that this manuscript is a cohort profile, the strengths/limitations could be tightened and more specifically describe the value of the cohort, for example, by stating that it includes people that cover the whole range of ID (from mild to severe)."

RESPONSE
This section has been reviewed to clarify where 'cohort' and 'study' are the most appropriate terms to use (article summary, p. 3). Further points relating to the cohort, such as the fact it includes children from mild to severe ID ('Wave 1 Cohort Description', p. 8), have been included.
1.4 "On p 6. Lines 4-6, the authors indicate that the sample includes 1000 families of children with ID. I wonder if it is worth specifying at this point that the families were all living in the UK at the time of recruitment." RESPONSE This information has been added.
1.5 "On p. 6 lines 35-36, the authors state that telephone interviews were completed by 649 primary caregivers. It may be helpful to indicate whether the characteristics of these families differ in any way to the characteristics of families who chose not to participate in the telephone interviews. I appreciate that this is in the strengths and limitations section, but it could be presented more succinctly."

RESPONSE
We have added a sentence at this point in the paper ('Cohort Description', p. 6) to highlight where the information comparing the interview cohort and the overall cohort can be found. More complete statistical information has then been added in the findings to date section (pp. 18-20), and this is also summarized succinctly in the strengths and limitations (pp. 22-23).
1.6 "Table 2 (presented on p. 11) describes the measures used within the study and indicates that they are measured at T1 and T2. Does this mean that these measures were collected during wave 1 and wave 2?" RESPONSE Yes, these measures were collected during Wave 1 and Wave 2the table has been updated to refer to W1 and W2 rather than T1 and T2, and these are defined in the note below the tables (see Table 3, pp.14-17).
1.7 "I would like to see a more detailed description of the child with ID. For example, the mean scores (and range) on the Vinelands that were collected and whether the authors collected any information about cognitive assessments that families could report, e.g., based on previous diagnostic assessments." RESPONSE Further information on the child, including mean scores and range on the Vineland as well as medical comorbidities, have been included in Table 1 (pp.11-12), as well as summarized in the text (such as Wave 1 Cohort description, pp. 7-9, and Findings to Date,. No cognitive assessments were conducted, and this is now discussed in the strengths and limitations (p.22).
1.8 "In the description of the primary caregiver and family, it would be helpful to know how many siblings were in each family and whether the siblings had any diagnoses, such as ID or ASD."

RESPONSE
This information has been added to Table 2 (pp.13-14), which now focuses on the sociodemographic information for the caregiver and family.
1.9 "In the cohort description, I would also like to know whether the authors collected information on other genetic conditions typically associated with ID, aside from autism and Down Syndrome (for example, Fragile X, tuberous sclerosis, Williams Syndrome, Cornelia De Lange etc.). Similarly, did the authors collect any information about medical comorbidities (e.g., epilepsy, cerebral palsy), which may affect family wellbeing over and above the ID on its own? It would be worthwhile to present this information in the description of the cohort." RESPONSE Information on the child (including diagnoses and medical co-existing conditions) has now been added to the text (p. 8) and Table 1 (pp.11-12) to provide a more complete description of the children and their families.
1.10 "The authors have included information about the proportion of families living in the most deprived areas of the UK. It would be helpful to see where the participating families came from across the UK, perhaps using a visual?"

RESPONSE
Location by UK country is now reported for families in Table 2 (pp. 13-14) and in the text (Wave 1 Cohort description, p. 8). We have chosen not to add a visual so as not to take up unnecessary space.
1.11 "Much of the information in the 'Findings to Date' section belongs with the cohort description, as the authors are referring to the characterisation of the sample. Have there been any key findings or publications related to family wellbeing that have come from this sample?"

RESPONSE
Our understanding of a Cohort Profile paper was that we should focus on describing the achieved cohort. No findings have been reported to date, and findings addressing the research questions will be reported in future papers. Any future publications (none currently exist) will cite the cohort paper. Therefore, this manuscript focuses on the cohort description as well as the background to the overall study.
1.12 "The families were asked to describe the severity of their child's ID. It would be helpful to know how this was operationalised for the families." RESPONSE A description of how severity of ID was defined for parent report has been added to the following section: Wave 1 Cohort Description (p. 8).
1.13 "The authors could provide more specific details about the questions that they hope to answer using this cohort and the rationale for future work."

RESPONSE
Further details have been added to Future Directions (p. 21) to clarify some of the questions that will be explored with this cohort.
1.14 "In my opinion, the way that the comparisons of the characteristics of the families that did and did not take part in the telephone interviews is not very meaningful. Simply stating that one group had a higher mean score than the other, without indicating whether this difference was significant, nor an effect size or confidence intervals, does not tell us very much. I think this section could be reworked and presented more succinctly."

RESPONSE
The section on characteristics of the families that did and did not take part in the telephone interview has been reworked, and now includes additional statistics allowing meaningful comparison. The findings are discussed in Findings to  and are summarized succinctly in Strengths and Limitations (pp. 22-23).

Reviewer #2 comments:
2.1 "However, the data as presented seems limited in order to make any clear assessment of the value of the study. In Table 1. SES and demographic data on Wave 1 information is presented. In Table 2, measures used within the study are presented as well. Notably, for most of the measures presented, the majority (> 50%, based on my calculations) were reported as being already completed by the parent. Yet very limited amounts of this were presented (see comment #5 below and page 19 of the manuscript). It is not clear to this reviewer why this data was not presented, as this precludes one's ability to adequately assess this manuscript. It more data is not available, then it is not stated what is the value and justification of publishing this manuscript at this stage, as opposed to waiting for completion of the next stage of data collection." RESPONSE See response to Reviewer 1 1.11. Also, in responding to points from both reviewers, more information about the cohort has been added to the paper.

RESPONSE
The suggested references have been added and the approximate prevalence rate reported has been revised (Introduction, p. 3).
2.3 "Besides noting the goal to "explore correlates of…", It might be valuable to examine specific questions that the literature currently does not address with focused hypothesis that can be addressed. Thus, for the example the authors in the introduction note the increased risk of both maternal and paternal psychiatric morbidity in those having a child with ID. What further information might the current study provide in this respect that justifies further study."

RESPONSE
The Future Directions section has been updated to provide a more detailed summary of future areas of research using data from this cohort (p. 21). However, given our understanding of the purpose of a cohort profile, we have not made further changes.

2.4
"It would be helpful to make comparison to other large cohort studies from other countries."

RESPONSE
Two example cohort studies from other countries have now been referenced in this section to acknowledge the international context (Strengths and limitations, p. 21). However, our main point here was about the selection of measures that would provide opportunities for comparison with other UK datasets and not comparison with other international datasets.
2.5 "Given the large amount of information obtained from the parents, why not simply ask the parent what educational setting the child is attendingas this would provide at least a preliminary correlation with the function of the child."

RESPONSE
Educational setting was included in Table 1. This has now also been added to the text alongside a summary of parent-reported intellectual disability severity and VABS scores for those who completed the telephone interview (Wave 1 Cohort Description, p. 8). Limitations of this approach are discussed in the Strengths and Limitations (p. 22).
2.6 "From my reading of the manuscript, the above quoted paragraph contains the only information regarding results of measuresand specifically comparing parents who completed the phone interview vs. those that did not. Why is this information not located on page 15 under the heading "FINDINGS TO DATE"? Clarification of this point is important to allow the reviewer to understand why only this information was presented and not others. More complete statistical data, such as standard deviation, would also be helpful."

RESPONSE
As requested, we have moved this information to 'Findings to date' (pp. 18-20) and we added further information to provide a clearer picture of those who did, and did not, take part in the telephone interview.

CONCLUDING COMMENTS
We have included a 'marked copy' with changes marked clearly as well as a 'clean' version of the updated manuscript. We thank the two reviewers for their feedback and consideration of this manuscript and we look forward to seeing our paper published with BMJ Open. Whilst making revisions, we took the opportunity to carry out a careful check of the data, and have included minor updated numbers in the tables and text where needed.

Lauren Taylor
King's College London, Institute of Psychiatry, Psychology and Neuroscience, UK REVIEW RETURNED 18-Dec-2019

GENERAL COMMENTS
Thank you for the opportunity to review the revised manuscript titled, "Cohort Profile: the 1,000 Families Study, a UK multi-wave cohort investigating the wellbeing of families of children with intellectual disabilities." This manuscript describes a cohort of 1,000 families of children with an intellectual disabilities, who are taking part in a study designed to investigate wellbeing in these families. The authors were very responsive to prior review comments and have subsequently made substantial changes in response to the reviewers comments. I have only very minor suggestions for further revision.
On the whole the revised manuscript more clearly distinguished between the 1,000 Families Study and the description of the cohort participating in the study. The additional detail about the child with intellectual disability also helped to contextualise the information that was presented in the manuscript.
My only suggestion is that there is a section heading for STUDY DESCRIPTION (or something similar), with following sections for Study aims, Wave 1 data collection, Wave 2 data collection, Study funding, measures, PPI & Ethics, because these are all general aspects of the 1,0000 Families Study. This would move the heading for COHORT DESCRIPTION further down the paper and would more clearly link the description of the cohort with information about the inclusion/exclusion criteria and cohort description/sample characteristics. It may also be helpful to open this section with a statement that the focus of the rest of the manuscript is a description of the cohort participating in the 1,000 Families Study. There is format problem in the references section in regard to reference #2 that should be corrected. _______________________________________________________ ______________________ Review response to Authors' Revisions Reviewer #2 comments: 2.1 "However, the data as presented seems limited in order to make any clear assessment of the value of the study. In Table 1. SES and demographic data on Wave 1 information is presented. In Table 2, measures used within the study are presented as well. Notably, for most of the measures presented, the majority (> 50%, based on my calculations) were reported as being already completed by the parent. Yet very limited amounts of this were presented (see comment #5 below and page 19 of the manuscript). It is not clear to this reviewer why this data was not presented, as this precludes one's ability to adequately assess this manuscript. It more data is not available, then it is not stated what is the value and justification of publishing this manuscript at this stage, as opposed to waiting for completion of the next stage of data collection." RESPONSE See response to Reviewer 1 1.11. Also, in responding to points from both reviewers, more information about the cohort has been added to the paper. Reviewer: OK 2.3 "Besides noting the goal to "explore correlates of…", It might be valuable to examine specific questions that the literature currently does not address with focused hypothesis that can be addressed. Thus, for the example the authors in the introduction note the increased risk of both maternal and paternal psychiatric morbidity in those having a child with ID. What further information might the current study provide in this respect that justifies further study." RESPONSE The Future Directions section has been updated to provide a more detailed summary of future areas of research using data from this cohort (p. 21). However, given our understanding of the purpose of a cohort profile, we have not made further changes. Reviewer: Unfortunately, I do not agree. If the goal of this study is to describe a cohort (see above highlighted in yellow), then a comparison with other cohort studies is in order.

REVIEWER
2.5 "Given the large amount of information obtained from the parents, why not simply ask the parent what educational setting the child is attendingas this would provide at least a preliminary correlation with the function of the child." RESPONSE Educational setting was included in Table 1. This has now also been added to the text alongside a summary of parent-reported intellectual disability severity and VABS scores for those who completed the telephone interview (Wave 1 Cohort Description, p. 8). Limitations of this approach are discussed in the Strengths and Limitations (p. 22).
Reviewer: OK 2.6 "From my reading of the manuscript, the above quoted paragraph contains the only information regarding results of measuresand specifically comparing parents who completed the phone interview vs. those that did not. Why is this information not located on page 15 under the heading "FINDINGS TO DATE"? Clarification of this point is important to allow the reviewer to understand why only this information was presented and not others. More complete statistical data, such as standard deviation, would also be helpful." RESPONSE As requested, we have moved this information to 'Findings to date' (pp. 18-20) and we added further information to provide a clearer picture of those who did, and did not, take part in the telephone interview.
Reviewer: OK

VERSION 2 -AUTHOR RESPONSE
Reviewer #1 comments: 1.1 My only suggestion is that there is a section heading for STUDY DESCRIPTION (or something similar), with following sections for Study aims, Wave 1 data collection, Wave 2 data collection, Study funding, measures, PPI & Ethics, because these are all general aspects of the 1,0000 Families Study. This would move the heading for COHORT DESCRIPTION further down the paper and would more clearly link the description of the cohort with information about the inclusion/exclusion criteria and cohort description/sample characteristics. It may also be helpful to open this section with a statement that the focus of the rest of the manuscript is a description of the cohort participating in the 1,000 Families Study.

RESPONSE
The two subtitles have been added as requested: STUDY DESCRIPTION (p.5) and COHORT DESCRIPTION (p.18) along with a sentence introducing the latter section (p.18) Reviewer #2 comments: 2.1 It would provide clarification to the reader if the stated aims of this being a description of the cohort appear in both the abstract and in the manuscript. What the goals of the cohort study should be mentioned in a separate context.