Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12615000360516
Ethics application status
Approved
Date submitted
2/03/2015
Date registered
21/04/2015
Date last updated
12/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The ATLAS (Active Teen Leaders Avoiding Screen-time) and NEAT (Nutrition and Enjoyable Activity for Teens) school-based health-related fitness programmes for adolescents
Scientific title
Cluster randomised controlled trial of two school-based gender-targeted programmes aimed at improving muscular fitness and key health behaviours among adolescent boys and girls.
Secondary ID [1] 286224 0
Australian research council (FT140100399)
Universal Trial Number (UTN)
Trial acronym
ATLAS and NEAT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Poor health-related fitness
 294270 0
Physical inactivity
 294446 0
Psychological wellbeing
 294447 0
Sedentary behaviour
 294448 0
Obesity 294449 0
Condition category
Condition code
Public Health 294590 294590 0 0
Health promotion/education
Diet and Nutrition 294591 294591 0 0
Obesity
Mental Health 294592 294592 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ATLAS and NEAT are two multi-component school-based physical activity and sedentary behaviour interventions originally designed for and evaluated among low-income adolescent boys and girls, respectively. The original 'ATLAS' and 'NEAT Girls' programs included multiple components that could not be disseminated in a cost effective manner. Therefore, the intervention strategies and materials have been revised for sustainability and delivery without the support of the research team. Although the original ATLAS and NEAT programs targeted the same outcomes (i.e., both were obesity prevention programs targeting key weight-related behaviours), there were a number of key differences in regards to the selected intervention strategies. Consequently, the revised versions of ATLAS and NEAT have been amended to be identical in terms of the structure and intervention components used. The key difference between the revised versions of ATLAS and NEAT is the gender-targeting strategies which aim to engage and motivate adolescent boys and girls, respectively, in each program. Although the efficacy of each of these programs has previously been evaluated, the evaluation was conducted among culturally homogenous study samples demonstrating risk-factors for obesity and related health concerns (i.e., low-active, high screen-based sedentary time). In light of this, and in recognition of the modifications made to the programs, there is a need to further evaluate the efficacy of the ATLAS and NEAT programs among a representative sample of adolescents prior to dissemination.


The trial will involve the evaluation of the revised ATLAS and NEAT school-based health-related fitness programs using a cluster RCT design in sixteen public secondary schools (8 intervention and 8 control schools). Both programs (i.e., ATLAS and NEAT) will be delivered simultaneously at the study schools during the intervention period. The students will receive the intervention over 10 weeks, with the total duration of the intervention (i.e., from baseline assessments to final follow-up assessments) being 12-months. The revised ATLAS and NEAT programs will both include the following implementation strategies and intervention components:

Implementation strategies:

1) Professional learning workshops for teachers: The research team will plan and deliver 1 full-day professional development workshop for 4 teachers at each of the intervention schools (2 PE teachers [1 male and 1 female] and 2 non-PE teachers [1 male and 1 female]). The workshop will occur in the school term prior to the commencement of the school sport sessions and will introduce teachers to the intervention aims and objectives. It will also focus on strategies to promote health-related fitness and physical activity, reduce sedentary behaviour, and improve social and emotional well-being in adolescents. Teachers will be provided with opportunities to improve their confidence and competence to model and teach resistance training and fitness skills to students. The workshop will provide teachers with an introduction to the principles of Self-Determination Theory (SDT), embedded through the SAAFE (Supportive, Active, Autonomous, Fair and Enjoyable) teaching principles, which will be used to guide their teaching during their facilitation of the ATLAS and NEAT programs.

2) Provision of fitness equipment and session resources: Schools will be provided with an equipment pack for conducting health-related fitness activities during the enhanced school sport sessions. The equipment pack will include a class set of Gymsticks (i.e., elastic band resistance training devices), boxing gloves and focus pads, skipping ropes, agility ladders, and hanging gym handles for performing suspended resistance training exercises. In addition, each school will receive program resources including circuit and workout cards and a teacher handbook to assist with program planning and delivery.

3) Ongoing professional support: Members of the research team will observe four school sport sessions at each school over the study period (2 ATLAS sessions and 2 NEAT sessions). Teachers will be provided with constructive feedback and on-going professional support. This component will also be used to assess intervention fidelity (i.e., compliance with the intended sport sessions structure and adherence to the SAAFE teaching principles outlined during the pre-program professional learning workshop).

Intervention components:

1) Interactive seminar for students: Participating students will attend 1 interactive seminar delivered by participating teachers at the study schools (30 minutes). The seminars will be delivered at the beginning of the program and will outline the key behavioural messages of the programs. In addition, the seminar will provide students with strategies to increase their physical activity, reduce their sedentary time and improve their nutrition.

2) Enhanced school sport sessions: Students will participate in 10 weeks of enhanced school sport (1 session/week for approx. 90 minutes). These sessions will be delivered by teachers and will include a range of vigorous physical activities designed to engage students and improve health-related fitness. Each session will include the following components: warm-up, resistance training skill development, high-intensity fitness challenge, small sided active games/yoga/Pilates/boxing fitness, and cool down.

3) Lunch-time physical activity sessions: Students will participate in 5 weeks of lunch-time physical activity sessions (1 session/ week for approx 20 minutes) during the second half of the program (i.e., the last five weeks). These sessions will be supervised by teachers but will be organised and led by students. The aim of these sessions is to provide students with the opportunity for more vigorous physical activity during the school week and to provide students with ownership and responsibility of their own physical activity.

4) Purpose-built smartphone applications: Two smartphone applications (1 for ATLAS and 1 for NEAT) will be provided to students free of charge at the commencement of the school sport sessions. The smartphone applications will be used for: (i) providing tailored informational and motivational messages; (ii) self-monitoring of physical activity; (iii) goal setting; (iv) conducting self-directed workouts; and (v) peer assessment of resistance training skills. Students will be provided with instructions on how to use the smartphone applications and will be encouraged to explore and use each of the features. However, there will be no explicit prescription for use of this component during the program. Engagement with the ATLAS and NEAT apps will be at the discretion of the participating students.
Intervention code [1] 291241 0
Lifestyle
Intervention code [2] 291242 0
Prevention
Intervention code [3] 291243 0
Behaviour
Comparator / control treatment
Wait list control. Students in the control group will receive standard treatment (ie. regular school sport program and health and physical education curriculum) during the intervention period and will receive a condensed version of the intervention after the 12-month follow-up assessments.
Control group
Active

Outcomes
Primary outcome [1] 294366 0
Upper body muscular endurance (student): assessed using 90-degree push-up test (Cooper Institute for Aerobics Research 2004)
Timepoint [1] 294366 0
Baseline, 6-month and 12-month
Primary outcome [2] 294367 0
Lower body muscular strength (student): assessed using a standing long jump test (Ruiz et al., 2011)
Timepoint [2] 294367 0
Baseline, 6-months and 12-month
Secondary outcome [1] 313140 0
Body mass index (student). Height and weight will be measured using a portable digital scale and stadiometer. Body mass index will be determined using the standard method (weight [kg] / height [m^2]).
Timepoint [1] 313140 0
Baseline, 6-month and 12-month
Secondary outcome [2] 313141 0
Cardio-respiratory fitness (student): assessed using a sub-maximal step test validated among children and adolescents (Francis & Feinstein, 1991)
Timepoint [2] 313141 0
Baseline, 6-month and 12-month
Secondary outcome [3] 313142 0
Flexibility: assessed using back-saver sit and reach test (Cooper Institute for Aerobics Research 2004)
Timepoint [3] 313142 0
Baseline, 6-month and 12-month
Secondary outcome [4] 313143 0
Resistance training skill competency (student): assessed by video analysis and subsequent grading using the Adolescent Resistance Training Skills Battery (RTSB) (Lubans et al., 2014), which includes the following exercises- body weight squat, push-up, lunge, suspended row, standing overhead press and front support with chest touches.
Timepoint [4] 313143 0
Baseline, 6-month and 12-month
Secondary outcome [5] 313144 0
Physical activity (student): Habitual physical activity will be assessed using a single-item self report measure developed for use with adolescents (Scott et al., 2015). Participation in resistance training-based physical activity will be assessed using another single item self-report measure previously used with adolescents (Martinez-Gomez et al., 2011). In addition, physical activity will be assessed objectively among a random sub-sample of participants using GeneActive wrist-worn accelerometers.
Timepoint [5] 313144 0
Baseline (all measures), 3-month (accelerometry-only), 6-month (self-report-only) and 12-months (all measures)
Secondary outcome [6] 313145 0
Global self-esteem (student): assessed using items from the Physical Self-Description Questionnaire - short form (Marsh et al., 2010)
Timepoint [6] 313145 0
Baseline, 6-month and 12-month
Secondary outcome [7] 313146 0
Self-reported physical fitness (student and teacher): assessed using the International Fitness Scale (IFIS) (Sanchez-Lopez et al., In press)
Timepoint [7] 313146 0
Baseline, 6-month, 12-month
Secondary outcome [8] 313147 0
Psychological well-being (student): assessed using Diener's psychological flourishing scale (Diener et al., 2009)
Timepoint [8] 313147 0
Baseline, 6-month and 12-month
Secondary outcome [9] 313149 0
Resistance training self-efficacy (student): assessed using a four-item scale developed for use with adolescents (Lubans et al., 2011)
Timepoint [9] 313149 0
Baseline, 6-month and 12-month
Secondary outcome [10] 313150 0
Recreational screen-time (student): assessed using a modified version of the Adolescent Sedentary Activity Questionnaire (ASAQ) (Hardy et al., 2007)
Timepoint [10] 313150 0
Baseline, 6-month and 12-month
Secondary outcome [11] 313151 0
Key dietary behaviours (student): sweets and junk food snack intake, and sugar-sweetened beverage consumption will be assessed using self-report items taken from the Australian Child and Adolescent Eating Survey (Watson et al., 2009)
Timepoint [11] 313151 0
Baseline, 6-months and 12-months
Secondary outcome [12] 313152 0
Sleep time and sleep quality (student): assessed by self-report using items from the School Sleep Habits Survey (Wolfson R & Carskadon, 1998)
Timepoint [12] 313152 0
Baseline, 6-months, 12-months
Secondary outcome [13] 313160 0
Motivation to participate in resistance training (student): assessed using an adapted version of the Behavioural Regulations in Exercise Questionnaire-2 (BREQ-2) (Markland and Tobin, 2004)
Timepoint [13] 313160 0
Baseline, 6-month and 12-month
Secondary outcome [14] 313162 0
Confidence to teach health-related fitness activities (teacher): assessed using an adapted version of an existing scale developed for use with classroom teachers (Morgan & Burke, 2007). The original scale was used to assess confidence to teach physical education. The items were adapted to apply specifically to health-related fitness activities.
Timepoint [14] 313162 0
Baseline, 6-month and 12-month
Secondary outcome [15] 313163 0
Perceived barriers to teaching health-related fitness activities (teacher): assessed using an adapted version of an existing scale developed for use with classroom teachers (Morgan & Hansen, 2008). The original scale was used to assess perceived barriers to teaching specific physical education content. The items were adapted to apply specifically to health-related fitness activities
Timepoint [15] 313163 0
Baseline, 6-month and 12-month
Secondary outcome [16] 313692 0
Autonomous motivation for physical activity (student): assessed using the autonomous motivation sub-scale of the Behavioural Regulations in Exercise Questionnaire-2 (BREQ-2) (Markland Tobin, 2004)
Timepoint [16] 313692 0
Baseline, 6-month and 12-month

Eligibility
Key inclusion criteria
Eligible schools are public secondary schools. Eligible participants must be males or females in grade 9 at the study schools.
Minimum age
12 Years
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Students will be ineligible if they have a medical condition or physical injury preventing testing or participation in physical activity.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sixteen secondary schools from the Hunter, Central Coast and Sydney Regions will be invited to participate in the study. School principals will be sent an Information Statement and Consent Letter inviting their school to participate in the study. Once schools have expressed interest in the project, the project manager will contact the schools and request an opportunity to present the research proposal to the physical education teaching staff. All grade 9 students at consenting schools will be invited to participate in the study following a presentation from a member of the research team. Once baseline data has been collected, randomisation will occur at the school level.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The project will use a group randomised controlled trial design with schools randomly allocated to intervention or wait-list control groups for the duration of the study. Schools will be match-paired, based on size and location, then randomly allocated by an independent researcher to the intervention or control group using a computer-based random number producing algorithm.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Wait list control design. Participants assigned to the control group will receive a condensed version of the intervention following the 12-month follow-up assessments.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Power calculation:
Sample sizes calculations have been based on estimated effect sizes for the primary outcome of muscular fitness assessed using the push-up and standing long jump tests (Cooper institute, 2013). Although the health benefits of muscular fitness are now well established (Smith et al., 2014), there is lack of consensus regarding the clinical significance of changes in muscular fitness in young people. In accordance with CONSORT guidelines, our power calculations were adjusted for the clustering of effects at the class level. We estimate that we will require a total of 640 students from 16 schools in order to achieve 80% power with alpha levels set at p < .05. Based on our pilot studies, we anticipate an effect size of d = 0.4 for muscular fitness (Lubans et al., 2011). We adjusted for clustering using a correction factor of [1+ (m-1)* p], where m = participants per class and p = the intra-class correlation coefficient (ICC). Assuming a class size of 20 participating students, two classes per school and an ICC for muscular fitness of 0.09, the correction factor is 2.7 [i.e., 1 + (20-1)*0.09]. Allowing for 10% loss to follow-up at 6-months and a further 10% loss at 12-months, the required sample size is 640 students from 16 schools (16 intervention classes and 16 control classes). The study will be adequately powered to detect significant between group differences at the primary end-point (6-months) and at follow-up (12-months).


Outcome analysis:
Statistical analyses of the primary and secondary outcomes will be conducted using linear mixed models in SPSS statistics for Windows, Version 21 (2010 SPSS Inc., IBM Company Armonk, NY), with alpha levels set at p <0.05. The models will be used to assess the impact of treatment (intervention or control), time (treated as a categorical variable with levels baseline, 6- and 12-months) and the group-by-time interaction, using random effects to account for the clustered nature of the data. The primary time-point will be 6-months from baseline. Compared to complete case analyses, mixed models include available data for all participants in the analysis and are thus more robust to bias and loss of efficiency. Mixed model analyses are consistent with the intention-to-treat principle, assuming the data are missing at random (White et al., 2012). The validity of this assumption will be explored by assessing relationships between missingness and observed values of covariates and previous outcomes. Multiple imputation and/or pattern mixture modelling will be considered as a sensitivity analysis if the dropout rate is substantial. Potential moderators (i.e., sex, household socio-economic status, and initial weight status) will be explored using linear mixed models with interaction terms and sub-group analyses will be conducted if p <0.1.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/04/2015
Actual
28/04/2015
Date of last participant enrolment
Anticipated
26/06/2015
Actual
18/06/2015
Date of last data collection
Anticipated
Actual
29/06/2016
Sample size
Target
640
Accrual to date
Final
627
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 290802 0
Government body
Name [1] 290802 0
Australian Research council
Country [1] 290802 0
Australia
Funding source category [2] 290803 0
Government body
Name [2] 290803 0
New South Wales Department of Education and Communities School Sport Unit
Country [2] 290803 0
Australia
Primary sponsor type
University
Name
University of Newcastle
Address
University Drive
Callaghan, NSW 2308
Country
Australia
Secondary sponsor category [1] 289483 0
Individual
Name [1] 289483 0
Prof David Lubans
Address [1] 289483 0
Priority Research Centre in Physical Activity and Nutrition
Level 3 ATC building
University of Newcastle
University Drive
Callaghan, NSW 2308
Country [1] 289483 0
Australia
Secondary sponsor category [2] 289484 0
Individual
Name [2] 289484 0
Prof Philip Morgan
Address [2] 289484 0
Priority Research Centre in Physical Activity and Nutrition
Level 3 ATC building
University of Newcastle
University Drive
Callaghan, NSW 2308
Country [2] 289484 0
Australia
Secondary sponsor category [3] 289485 0
Individual
Name [3] 289485 0
Prof Ronald Plotnikoff
Address [3] 289485 0
Priority Research Centre in Physical Activity and Nutrition
Level 3 ATC building
University of Newcastle
University Drive
Callaghan, NSW 2308
Country [3] 289485 0
Australia
Secondary sponsor category [4] 289486 0
Individual
Name [4] 289486 0
Mr Jordan Smith
Address [4] 289486 0
Priority Research Centre in Physical Activity and Nutrition
Level 3 ATC building
University of Newcastle
University Drive
Callaghan, NSW 2308
Country [4] 289486 0
Australia
Secondary sponsor category [5] 289487 0
Individual
Name [5] 289487 0
Dr Narelle Eather
Address [5] 289487 0
Priority Research Centre in Physical Activity and Nutrition
Level 3 ATC building
University of Newcastle
University Drive
Callaghan, NSW 2308
Country [5] 289487 0
Australia
Secondary sponsor category [6] 289488 0
Individual
Name [6] 289488 0
A/Prof Chris Lonsdale
Address [6] 289488 0
Institute for Positive Psychology and Education
Australian Catholic University
25A Barker Road
Strathfield NSW 2135
Country [6] 289488 0
Australia
Secondary sponsor category [7] 289489 0
Individual
Name [7] 289489 0
Dr Louisa Peralta
Address [7] 289489 0
Faculty of Education and Social work
Room 448, A35 - Education Building
The University of Sydney
NSW 2006
Country [7] 289489 0
Australia
Secondary sponsor category [8] 289490 0
Individual
Name [8] 289490 0
Dr Toni Hilland
Address [8] 289490 0
Faculty of Education
Monash University
29 Ancora Imparo Way
VIC 3800
Country [8] 289490 0
Australia
Secondary sponsor category [9] 290479 0
Individual
Name [9] 290479 0
Professor Jo Salmon
Address [9] 290479 0
School of Exercise and Nutrition Sciences, Deakin University,
221 Burwood Highway, Burwood, VIC, 3125
Country [9] 290479 0
Australia
Secondary sponsor category [10] 290480 0
Individual
Name [10] 290480 0
Professor Anthony Okely
Address [10] 290480 0
Early Start Institute, University of Woolongong, Northfields Avenue, Woolongong, NSW, 2522
Country [10] 290480 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292428 0
University of Newcastle Human Research Ethics Committee
Ethics committee address [1] 292428 0
University of Newcastle
University Drive
Callaghan, NSW 2308
Ethics committee country [1] 292428 0
Australia
Date submitted for ethics approval [1] 292428 0
15/09/2014
Approval date [1] 292428 0
23/10/2014
Ethics approval number [1] 292428 0
H-2014-0312
Ethics committee name [2] 292429 0
New South Wales Department of Education and Communities ethics committee
Ethics committee address [2] 292429 0
Policy, Planning and Reporting Directorate
NSW Department of Education and Communities
Level 1, 1 Oxford Street
Darlinghurst NSW 2010
Ethics committee country [2] 292429 0
Australia
Date submitted for ethics approval [2] 292429 0
17/09/2014
Approval date [2] 292429 0
18/11/2014
Ethics approval number [2] 292429 0
2012121

Summary
Brief summary
The aim of this study is to evaluate the revised versions of the ATLAS and NEAT school-based health-related fitness (HRF) programs for adolescents using a cluster randomised controlled trial in 16 secondary schools located in the Hunter, Central Coast and Sydney regions of New South Wales (NSW), Australia. The revised ATLAS and NEAT programs will be delivered over 10-weeks to male and female students in grade 9 at the study schools. The ATLAS and NEAT programs include a range of strategies aimed at improving HRF and social and emotional well-being among adolescents. Assessments will occur at baseline, 6-months, and 12-months. The primary outcome is muscular fitness (push-ups and standing long jump). Secondary outcomes for students include perceived and actual HRF, physical activity, resistance training skill competency, social and emotional well-being, self-esteem, screen-time, consumption of discretionary foods, motivation for resistance training and physical activity, sleep time and sleep quality. Hypothesised mediators of physical activity and HRF will also be explored. Secondary outcomes for teachers include confidence to teach HRF activities, perceived barriers to teaching HRF activities, and perceived fitness.
Trial website
No website currently available.
Trial related presentations / publications
Lubans, D. R., Morgan, P. J., Dewar, D., Collins, C. E., Plotnikoff, R. C., Okely, A. D., . . . Callister, R. (2010). The Nutrition and Enjoyable Activity for Teen Girls (NEAT girls) randomized controlled trial for adolescent girls from disadvantaged secondary schools: rationale, study protocol, and baseline results. BMC Public Health, 10, 652-665.

Lubans, D. R., Morgan, P. J., Okely, A. D., Dewar, D., Collins, C. E., Batterham, M., . . . Plotnikoff, R. C. (2012). Preventing obesity among adolescent girls: one-year outcomes of the nutrition and enjoyable activity for teen girls (NEAT Girls) cluster randomized controlled trial. Archives of Pediatrics and Adolescent Medicine, 166(9), 821-827.

Dewar, D. L., Morgan, P. J., Plotnikoff, R. C., Okely, A. D., Collins, C. E., Batterham, M., ... & Lubans, D. R. (2013). The Nutrition and Enjoyable Activity for Teen Girls study: a cluster randomized controlled trial. American journal of preventive medicine, 45(3), 313-317.

Smith, J. J., Morgan, P. J., Plotnikoff, R. C., Dally, K. A., Salmon, J., Okely, A., D.,, . . . Lubans, D. R. (2014). Rationale and study protocol for the ‘Active Teen Leaders Avoiding Screen-time’ (ATLAS) group randomized controlled trial: An obesity prevention intervention for adolescent boys from schools in low-income communities. Contemporary Clinical Trials, 37(1), 106-119.

Smith, J. J., Morgan, P. J., Plotnikoff, R. C., Dally, K. A., Salmon, J., Okely, A. D., . . . Lubans, D. R. (2014). Smart-phone obesity prevention trial for adolescent boys in low-income communities: The ATLAS RCT. Pediatrics, 134(3), e723-e731
Public notes

Contacts
Principal investigator
Name 55162 0
Prof David Lubans
Address 55162 0
Priority Research Centre in Physical Activity and Nutrition
University of Newcastle
University Drive
Callaghan NSW 2308
Country 55162 0
Australia
Phone 55162 0
+61 2 49212049
Fax 55162 0
Email 55162 0
[email protected]
Contact person for public queries
Name 55163 0
David Lubans
Address 55163 0
Priority Research Centre in Physical Activity and Nutrition
University of Newcastle
University Drive
Callaghan NSW 2308
Country 55163 0
Australia
Phone 55163 0
+61 2 49212049
Fax 55163 0
Email 55163 0
[email protected]
Contact person for scientific queries
Name 55164 0
David Lubans
Address 55164 0
Priority Research Centre in Physical Activity and Nutrition
University of Newcastle
University Drive
Callaghan NSW 2308
Country 55164 0
Australia
Phone 55164 0
+61 2 49212049
Fax 55164 0
Email 55164 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA school-based intervention incorporating smartphone technology to improve health-related fitness among adolescents: Rationale and study protocol for the NEAT and ATLAS 2.0 cluster randomised controlled trial and dissemination study.2016https://dx.doi.org/10.1136/bmjopen-2015-010448
N.B. These documents automatically identified may not have been verified by the study sponsor.