Steps Ahead: optimising physical activity and health in people with cystic fibrosis: Study Protocol for a pilot randomised trial

Dear Dr Sarah Rand,
 
Re: Steps Ahead: Optimising physical activity in adults with cystic fibrosis: Study Protocol for a pilot randomised trial
 
We sincerely thank you for your detailed and critical analysis of our article. Please find our responses below after your feedback (in bold). All changes have been made and are illustrated through italics and will be submitted in the second version of this article:
 
Thank you for asking me to review this interesting and very topical protocol.
The authors have made a very good effort at identifying the need for undertaking this study (which is even more relevant given the current circumstances around the world) for PWCF. As the authors correctly say there is an ever-increasing research base investigating telehealth for individuals with long term conditions such as CF so this is a pertinent and relevant study protocol.
 
Thank you for your positive response. We believe this is very timely research, particularly considering current circumstances and the current landscape for PWCF. We have attempted to address your concerns below to enhance the quality and transparency of our research.
 
Below are some specific section comments:
Title:
The title is a little confusing as health is all encompassing and can include many factors from physical to mental health. Physical activity itself also includes exercise so I think that the authors perhaps need to consider making the title a little more specific to the study aims and objectives. For example is exercise going to be assessed separately to physical activity from the steps data using perhaps HR data from the FitBits? In the abstract introduction quality and wellbeing have been used as secondary 'endpoints' - is this what the authors are referring to when they say health in the title. Perhaps the title should be more specific to reflect this? Also is the aim of the study not more focussed on investigating the ability of telehealth to impact on health behaviours in PWCF? There is no mention of telehealth or technology in the title - perhaps this should be considered?
 
Thank you for highlighting this.  We agree the title should be more specific and so this has been changed to “Steps Ahead: optimising physical activity in Adults with Cystic Fibrosis: Study protocol for a pilot randomised trial using wearable technology”.
 
Exercise is not being assessed separately to physical activity (step count data) in this present study. The Fitbit Charge 2 can measure ‘activity minutes’, through the use of heart rate (HR) data, however, this has not yet been evaluated as a valid and reliable measure for HR in people with CF. In fact, a recent study assessed HR data amongst 15 healthy participants and found that the Fitbit Charge 2 could underestimate HR by almost 30 beats per minute (Benedetto et al., 2018). Therefore, this pilot study is focusing on step count alone as a proxy measure for physical activity.
 
Thank you for this important observation. The use of the word health is broad and initially was used to refer to a number of variables described in the methods. As this is a pilot study, we are keen to investigate if this intervention will improve a range of clinical outcomes (including step count itself, lung function, exercise capacity, quality of life, wellbeing, and sleep). The word health in our study was used to broadly encompass these key components. However, our primary aim is to improve PA and so we have removed the word health from the title. We have provided further description of the health behaviours in the introduction and methods.
 
 Abstract:
The abstract is relatively clear however consistency with the title as suggested above is needed in terms of the aims of the study.
The manufacturer details are needed for the Fitbit and the Fitabase to ensure reproducibility.

The title has changed to reflect your comments above.
Manufacturer details have been added under the title primary outcome measure – Fitbit Charge 2, as follows:
“The Fitbit Charge 2 (Fitbit Inc.) will be used to record step count during this study with data uploaded to Fitabase (Small Steps Labs LLC).”
 
What does the online monitoring system actually do - there are limited details pertaining to this? What type of data is collected and how often and therefore what type of information is available to the healthcare professional.

Thank you for this comment which has been addressed in the script in the intervention “wearable technology section” as follows:
 
“Fitabase, the online monitoring system enables the physiotherapists to access step count data remotely. When a participant enables Bluetooth and syncs their Fitbit through the use of the Fitbit app, this automatically updates on the Fitabase website. This ensures that data is continuously collected over the full study duration. The data collected through the Fitbit Charge 2 and recorded on the Fitabase system are step count, activity minutes and sleep. However, for the purpose of this study, the researchers are only investigating step count alone. Any further research would require the Fitbit to be assessed under each of these conditions to ensure validity and reliability. This is outside the scope of this research.”
 
I think the authors need to be clear about what the text messages will include - is it only positive reinforcement plus changes to targets based on the weekly step counts etc (how will this be progressed? Is a standardised method going to be used for all participants? References perhaps needed for this. Or will it also include 'feedback'? What will the 'feedback' include? 

Thank you for this feedback. They following text has been added to the intervention section to ensure clarity around text messaging.
 
“The text messages in this study will be personalised, one-way texts with positive reinforcement on step count attained by the participant.  
A metanalysis found personalisation strategies such as using a participant name has been proven to increase intervention efficacy (Head et al., 2013) and tailoring messages is a key ingredient in text messaging interventions (Noar et al., 2007). Furthermore, one way communication is as effective as two-way dialogue (Head et al., 2013). Therefore, this study investigated one-way messages only.
An individualised message will be sent to each participant once a week, at a day and time chosen by the participant at the start of the intervention. The authors will follow a standardised approach. The message will address the participant by name and will have positive feedback in the form of encouragement and praise messages (Adams et al., 2013) in relation to their step count attained in the previous week. It will then focus on a physical activity related goal set by the subject and will sign off with a further positive comment.  Research has indicated that it is crucial to reinforce improvements to develop new behaviour or to strengthen a habit (Hovell et al., 2009, Glanz et al., 2008, Bandura, 2004).  Each time a participant meets his/her goal they will receive positive feedback. Participants who do not meet the goal will be provided with a positive comment in relation to their step count achieved to date and provided their next step goal. This is to avoid negative messages that could be discouraging (Adams et al., 2013).”
 
Is there a need for a wash-in period (to allow for the novelty effect) at the beginning of the study and/or a washout period between the 12 week time period to allow for the positive or negative impact of familiarisation of using a fitness tracker?

The authors acknowledge that no wash-in or wash-out period was applied and accept that there may be a novelty effect at the start of the study. This study included public and patient involvement (PPI) at the methodological development stage and both participants and clinicians felt that a 12-week intervention would be more readily accepted by this cohort as the study appointments could coincide with their routine clinic appointments. However, data will be regularly uploaded to Fitabase and therefore we can analyse and determine if there is a significant increase in steps in the first two weeks in comparison to subsequent weeks per participant and as a group.
 
A point of note: wearable technology is a more appropriate term rather than fitness tracker. 
Thank you for this comment. We agree with this and the term wearable technology has been used throughout the article.
 
Background:
There is a lack of data to support the statements being made throughout this section e.g. 'higher levels of exercise' what do the authors mean by higher and using what outcome measures?
More specific detail is required in terms of the evidence base being used to support the aims, objectives and methodology of this protocol under the 4 sub sections - CF, PA, telehealth and goal setting. A clear definition of physical activity is needed. Exercise is a sub section of physical activity and it is not clear if an specific 'exercise' intervention is planned via the SMS 'feedback' which should be outlined.

The authors thank the reviewer for this comprehensive feedback. A definition of PA has been added to the introduction along with further evidence to support PA in CF. There is no specific ‘exercise’ intervention planned via the feedback provided through the text messages. The study aims to look at step count behaviour only. The statements around ‘higher levels of exercise’ has been re-phrased. The following has been added/modified to the introduction:
 
“PA can be described as any bodily movement that causes an increase in energy expenditure above that of resting energy expenditure including leisure-time PA, occupational PA and exercise (Caspersen et al., 1985). Exercise and physical activity (PA) are widely documented in consensus statements as key components in the management of CF ( Castellani et al., 2018). PA has several positive benefits in this population as it has been shown to improve sputum clearance (Dwyer et al., 2009), bone mineral density (Gupta et al., 2019) and muscle strength (Burtin et al., 2013). More importantly, PA can improve aerobic capacity (Hebestreit et al., 2010) and it can slow the rate of decline in lung function  (Schneiderman et al., 2014), both of which are linked to increased survival in CF (Nixon et al., 1992). As a result, the optimisation of exercise and PA among PWCF is important, however, a Cochrane review found that there was a lack of evidence regarding strategies to promote PA in this population and consideration should be given towards telemedicine applications and health coaching ( Cox et al., 2013b).
 
Numerous subjective and objective methods are reported in the literature for the assessment of PA in adults with CF. Step count measurement can be used to quantify and monitor PA behaviours (Tudor-Locke and Bassett, 2004). Despite the clear benefits of PA in CF, a recent systematic review found that adults with CF fail to meet recommended PA and step count guidelines (Shelley et al., 2019). Therefore, interventions which aim to increase PA in this population are of considerable interest.
 
In addition to telehealth, goal setting and reviewing goals regularly should be considered to support patients with chronic illness ( Coleman & Newton, 2005). In order for goals to be achieved, feedback should be provided that reveals progress in relation to the goal ( Locke & Latham, 2002). Furthermore, setting specific goals should offer a plan to break PA goals into more practical, manageable steps ( Shilts et al., 2004) which should increase self-efficacy and hence promote continued regular PA levels ( Bandura, 2004). Previous literature from patient preference research and effective PA promotion approaches reports that successful strategies include specifically targeting PA (Conn et al., 2008), the use of behavioural strategies such as feedback and goal setting (Conn et al., 2008, Kosma et al., 2005) (George et al., 2012) and the ability to self-monitor (Conn et al., 2008). The Irish national framework for self-management includes goal setting and action planning in chronic disease management ( Chronic Conditions Working Group, 2017). PA interventions using pedometers have been shown to be more effective at increasing PA if they include step goals (Bravata et al., 2007). However, goal setting to increase PA in adults with CF is poorly investigated.”
 
In addition in the background reference to the need for an assessment of delivery and acceptability is made but this has not been mentioned in the abstract or introduction.

Thank you for highlighting this. The following has now been added to the introduction:
 
“This pilot randomised trial aims to explore the impact of wearable technology, text message personalised feedback and goal setting on PA and health outcomes in adults with CF. For the purpose of this study these specific health outcomes include lung function, aerobic capacity, body composition, quality of life, well-being and sleep. Poor sleep quality has been previously highlighted as an issue in adults with CF (Milross et al., 2002) and PA interventions can improve sleep quality in other populations (Yang et al., 2012, Lan et al., 2014).
 
In addition, it is important to conduct a qualitative analysis to evaluate the implementation, delivery and acceptability of the intervention as this is the key to the development of future research which this pilot study aims to inform. Therefore, semi structured interviews will be conducted with the study participants and with the healthcare professionals providing the intervention. This will aim to inform future studies in this evolving research area.”
 
Methods:
What do the authors mean by efficacy? Is engagement with the technology enough for the study to be deemed efficacious? Will engagement with the technology be recorded? 
The authors are referring to the ability of the tracker to change PA levels, FEV1 or exercise capacity (being the primary outcome measures).

Thank you for your feedback on this. The term efficacy is nebulous and so this has been changed to more concrete term reflecting what we aim to do in this study -

“This study represents a single centre pilot randomised trial which will compare the effect of wearable technology with personalised text message feedback and goal setting to wearable technology alone in adults CF.”

Efficacy refers to the ability of the wearable technology, text message feedback and goal setting to increase PA levels (being the primary measure). The following has been added in relation to engagement with the technology:

“Engagement with the technology will be monitored through systematic review of online data. Participants in both groups will receive a “reminder” message on his or her mobile phone if their data has not been synced via the Fitbit App in the previous seven days. This ensures that data is continuously collected over the full study duration.”

Will the outcome measures be measured during routine outpatient appointments - or will additional appointments need to be made? What will the additional burden (physical and time) be for the participants? Has there been any PPI used in the planning of this study to take this into account?

Thank you for highlighting this. We have added the following for clarification on appointments -

“Each adult with CF attends their routine clinic appointments every three months. Therefore, we chose this duration for our intervention to dovetail with routine CF care and limit the need for participants to attend on a more regular basis for testing appointments. This was decided through PPI (completed with adults with CF) and with clinician input. If the participant cannot attend on a particular clinic day, then they will be offered an additional appointment to suit their schedule.”
The cardiopulmonary exercise test (CPET) is only completed at annual assessment typically, and so, this will require additional time on their routine clinic appointment. It is aimed to conduct this CPET either pre or post clinic review. The anticipated time to complete the CPET is between eight to 12 minutes. 
 
Exclusion criteria - why have individuals with a FEV1<25% been excluded?

The following has been added to the exclusion section:
 
“Individuals with FEV₁ <25% would typically require supplemental oxygen for exercise and at this point may require transplant assessment. Furthermore, they are more likely to experience exacerbations and would not be suitable for a study over 24 weeks. This is a lower cutoff FEV₁ than most studies would include (Kriemler et al., 2013, Hebestreit et al., 2010, Klijn et al., 2004)”

The term PWCF who are pregnant rather than pregnancy should be used.

Thank you, this has been changed in the manuscript.
 
No mention of 'usual care' has been given and would be useful for the reader to understand with respect to physical activity advice and interventions that the participants normally receive.

Thank you for this suggestion which the authors agree would be helpful to include in the manuscript. We have added the following to the methods section of the article:
 
“Usual care would typically include PA and exercise advice as per Australian and New Zealand Cystic Fibrosis guidelines (Button et al., 2016). People with CF are advised to exercise for at least 30 minutes, five days a week. They are advised to include a combination of aerobic and resistance training. It is personalised depending on patient preference (Button et al., 2016).”

Randomisation: the lung function categories are confusing - <70% mild - should this not be 70% and above? 30-50% moderate - what about those with 51-69%.....?

Thank you for this comment. This was an oversight and has been adjusted as per below.
 
“Following this a minimisation randomisation procedure will be completed based on lung function, where FEV₁ of >80% predicted lung function will be classified as having mild lung disease. While those with an FEV₁ of 50-79% predicted lung function will be classified as having moderate lung disease, 30-49% as severe lung disease and <30% indicating severe lung disease (Ranu et al., 2011)”
 

Intervention - more detail is needed to clearly explain and outline all of the details pertaining to the initial information - how will this be provided - verbal or written form? What will it include? Etc.

We have endeavoured to provide more detail on the intervention in the manuscript as follows:
 
“Baseline activity levels will be obtained using an ActivPAL accelerometer as part of a parallel study which assesses PA levels in this group. This will be used to inform goal setting only. The data obtained from the ActivPAL will be discussed with the participant at baseline.  Data will be included if at least four full days (at least three weekdays and one weekend day) of measurements with a minimum of 10 hours (h) for the weekdays and 10 h for the weekends are measured (Freedson et al., 2005). Based on PPI it was reported by the participants that they did not want to wear an ActivPAL other than at baseline as it is a thigh worn device which is not ‘fashionable’. Similar concerns have been cited previously in the research (Dias et al., 2012).
 
“The intervention consists of wearable technology, text message feedback and goal setting.

Wearable technology:
If the participant is allocated to the intervention, they will be provided with wearable technology (Fitbit Charge 2), educated on how to use it, and this will also be linked to an online monitoring system (Fitabase). Participants will be encouraged to enable Bluetooth and upload data regularly.

Goal setting:
The physiotherapist will discuss the participant’s PA levels (as measured at baseline by an accelerometer) and individual patient centred PA goals will be set with each participant. These will be discussed with their physiotherapist to ensure they are specific, measurable, achievable, realistic and timed (SMART). They will be encouraged to write a minimum of three goals. Participants will be asked to set a step count target for week four, eight and 12 and consider ways to achieve these goals, both of which will be discussed with the physiotherapist during the baseline appointment. Goals will be individualised to the participant taking into account their preferences. Participants may also set goals related to health outcomes being assessed – for example, a participant may have a goal to improve lung function, aerobic capacity, sleep etc. during the study period. The text message feedback will refer to step goals only.  The participant will be given a copy of their goals.
 
Text message feedback:
The text messages in this study will be personalised, one-way texts with positive reinforcement on step count attained by the participant.   A metanalysis found personalisation strategies such as using a participant name has been proven to increase intervention efficacy (Head et al., 2013) and tailoring messages is a key ingredient in text messaging interventions (Noar et al., 2007). Furthermore, one way communication is as effective as two-way dialogue (Head et al., 2013). Therefore, this study investigated one-way messages only.
An individualised message will be sent to each participant once a week, at a day and time chosen by the participant at the start of the intervention. The authors will follow a standardised approach. The message will address the participant by name and will have positive feedback in the form of encouragement and praise messages (Adams et al., 2013) in relation to their step count attained in the previous week. It will then focus on a physical activity related goal set by the subject and will sign off with a further positive comment.  Research has indicated that it is crucial to reinforce improvements to develop new behaviour or to strengthen a habit (Hovell et al., 2009, Glanz et al., 2008, Bandura, 2004).  Each time a participant meets his/her goal they will receive positive feedback. Participants who do not meet the goal will be provided with a positive comment in relation to their step count achieved to date and provided their next step goal. This is to avoid negative messages that could be discouraging (Adams et al., 2013). If the participant does not achieve their target step count goal then the physiotherapist will set a target increase of 10% from the mean step count achieved in the previous week.

A sample text message is as follows:
Hi Paul, Well done on achieving an average daily step count of 7,600 steps this week. Next week aim to hit your goal of 8,000 steps. Keep up the good work! 
 
How will baseline physical activity be measured? Using the Fitbits provided or another accelerometer? How long will this be measured for? Specific details are needed here - number of hours and on which days - weekdays and/or weekends etc.
 
As per above previous comment above, baseline PA levels will be measured by an ActivPAL accelerometer (PAL technologies). This will not be further used in the study as based on PPI adults with CF will not comply to wear this device on subsequent testing. This has been added to the methods section of the article.

Goal setting intervention - what strategies and approach will be used for this? Will a specific standardised format be used for each participant? How many goals will be used? Will this be standardised?

Please see previous paragraph on goal setting. This will be illustrated under the Intervention section of the article.

As previously mentioned are wash-in and washout periods needed for data collection? Would a randomised crossover study design be more useful to account for this?

As mentioned above we felt that a wash-in and wash out period would not be necessary in a small pilot study that is 12 weeks in duration with a further 12 week follow up. A crossover study would increase the need for a washout period and would prolong the length of the study. We had considered a crossover design but we felt this was too complex for a small pilot study and taking into account overall patient burden.
 
Outcome measures:
Primary: In the abstract PA is included as a primary endpoint but listed as a secondary outcome here

Thank you for highlighting this. This has been changed. It is a primary outcome measure.

Is CPET an appropriate primary outcome measure - an exercise intervention has not been included or described in this protocol. Is the aim for fitness to be impacted or PA only? This needs to be clarified.

Thank you for this feedback. CPET is a secondary outcome measure.
 
Has the well validated supramaximal verification CPET protocol for PWCF been considered as an option?

Thank you for this suggestion. The supramaximal verification protocol will be used. This has been added to the methods section of the study.  

“Supramaximal verification be conducted to ensure a maximal effort during the CPET.  After an incremental CPET, participants will be provided with a ten-minute break. They will then be asked to complete a supramaximal exercise test (Causer et al., 2018, Saynor et al., 2013) whereby participants will exercise at 110% of their power output (as determined by CPET test previously). This test has been conducted amongst PWCF previously and has been deemed safe and ensures validity of the results which are obtained in a CPET test.”

More details are required regarding the 'ramp protocol' that has been referred to and a reference added. What outcomes will be used from the CPET - VO2 max only or will others be considered e.g. VE/VO2, RER as well as standard CPET outcomes in terms of duration, load etc. More details are needed.

Thank you for this comment. The following text has been added to the methods section under secondary outcome measures and “CPET”.

“The reference standard exercise test is an incremental cardiopulmonary exercise test (CPET), utilising a ramp protocol. The ramp protocol ensures that work rate is progressively and linearly incremented until maximal effort is achieved (Herdy et al., 2016). All standard CPET outcomes will be considered including duration, load, pulmonary ventilation (VE), Respiratory Exchange Ratio (RER), ventilatory equivalents for oxygen (VE/VO ₂) and for carbon dioxide (VE/VCO ₂).”

Is FEV1 only going to be used as a classification measure? If this is the case then it is not a primary outcome measure but purely a method of categorising the participants rather than a measure of change or a measure of the impact of the technology.
Are other PFTs measures going to be considered?
 
Thank you for highlighting this. FEV₁ will be used as a classification measure but will also be used to determine the effect that this intervention may have on FEV₁ as a secondary outcome measure. Furthermore, we will also consider other PFT’s such as FVC and FEF25-75. The following has been added to the methods section:
 
“Forced expiratory volume in one second (FEV ₁) will be used to classify the severity of CF lung disease for each participant. It will also be used to determine the effect the intervention may have on pulmonary function. Other pulmonary function measures such as % forced vital capacity (FVC) and forced expiratory flow (FEF25-75) will also be considered.”

Secondary
More detail regarding the step count data collection needed. How frequently will data be collected? How will this be analysed - how many timepoints? Will all 7 days be used or only those with a pre-specified number of hours data? Etc.
 
The data will be continuously collected throughout the study time period.
Every time the participant syncs their Fitbit, the data will automatically upload on to Fitabase.
The following has been added to the data analysis section: 

“Data will be collected over seven days and an average weekly step count will be obtained.  It is anticipated that step count data will be analysed to assess for a novelty effect in the first two weeks, at week six and 12 during the intervention and at week 18 and Week 24 for the follow up. A repeated measures ANOVA, controlling for baseline values and other potential confounders will be conducted.”

More detail is needed regarding the protocols for each of the outcome measures e.g. hand dynamometry - will it be a best of three measure, what unit of measurement will be used, will a standardised protocol be used - what does this include?

Thank you for this feedback. We have added more detail to the protocol in the methods section.

“The participant will be asked to stand and hold the dynamometer in by their side, with their elbow at 90 degrees and forearm in neutral. They will be instructed to squeeze the device as hard as possible. They will be provided with a 30 second rest period between each trial. The greater of two trials from each hand will be used and added together to give overall handgrip strength. This will be measured in kilograms (Martínez-García et al., 2020).
 
Will the participants complete the questionnaires independently or in the presence of a study team member?

Thank you for highlighting this. The following has been added to the Data Collection and Management section:
 
“All self-report measures will be completed by the participants independently, however a research assistant (RA) (AJ) will be available if there are any queries or concerns. These subjective assessments will be analysed by the RA who is blinded to group allocation.”

Why is sleep being used as an outcome measure? What is the relevance or need for this? It’s not clear. This perhaps comes back to my comment regarding a need for a clear definition from the outset for 'physical activity and health'.
 
Thank you for this suggestion. We have added the following to clarify these specific health outcomes in the introduction section:

“This pilot randomised trial aims to explore the impact of wearable technology, text message personalised feedback and goal setting on PA and health outcomes in adults with CF. For the purpose of this study these specific health behaviours include lung function, aerobic capacity, quality of life, well-being and sleep. Poor sleep quality has been previously highlighted as an issue in adults with CF (Milross et al., 2002) and PA interventions can improve sleep quality in other populations (Yang et al., 2012, Lan et al., 2014).”

There are a lot of outcome measures - again the burden to the participant needs to be considered? Has participant fatigue been considered? Are all measures necessary to answer the research question? 

Participant fatigue has been considered. The authors have used a PPI approach in the study design and set up and based on feedback participants were satisfied with timing and breaks between each outcome assessment. Furthermore, the adults with CF attending this CF centre would be familiar with most of these outcome measures which would be conducted as part of their annual assessment. As this is a pilot study the authors incorporated a range of outcome measures to answer the key research questions and to inform future research.

Data analysis: limited statistical analysis plans have been provided. Further details are needed and some reference to intention to treat analysis, missing data and drop outs is required. In addition it would be useful to have an idea as to the possible options for data display.

The following has been added to the data analysis section:
“Primary analyses will be performed according to intention-to-treat (ITT) principles with all participants who were originally allocated by randomisation and those who dropped out from the study. In case of missing values, a multiple imputation method, inverse probability weighing or mixed models will be used to handle the missing data. Data will be presented as means and SDs for data that is normalised and medians (IQR) for data that is skewed.”
 
Discussion:
The discussion is quite limited and a number of broad generalised statements have been made which require further detail and explanation to fully convince the reader of the rationale and need for this study.

The discussion has been revised with further detail added on the rationale and need for the study.

A clear and evidence based discussion as to the validity and reliability of the chosen wearable technology is also needed.

Thank you for highlighting this. This research has been conducted and has been submitted for publication. This research concluded that Fitbit Charge 2 ranged from weak to very strong correlations when compared to visual observation (0.34-0.84). The Fitbit Charge 2 underestimated step count by 2.8%-9.2%. This is within acceptable limits of variability based on previous research (Schneider et al., 2004). The following has been added to the methods:
 
“Prior to this intervention, the validity and reliability of the Fitbit Charge 2 to measure step count in CF was assessed by the same research group (Curran et al., 2020). Twenty-one participants were recruited from an adult CF Centre for a single session of testing. Participants walked for five minutes at five pre-determined speeds in a controlled testing environment (2, 2.5, 3, 3.5 and 4 miles per hour on a treadmill) and at three self-selected speeds on a corridor (slow, medium and fast). The Fitbit Charge 2 was compared to visual observation. It was found that the Fitbit Charge 2 ranged from weak to very strong correlations when compared to visual observation (0.34-0.84). The Fitbit Charge 2 underestimated step count by 2.8%-9.2%. This is within acceptable limits of variability based on previous research (Schneider et al., 2004).”
 
A brief reference to the fact that gene therapy will be monitored during the study has been made - this is a very important point and needs to be considered carefully. A clear outline of what 'other' data will be monitored during the study is also needed - e.g. hospital admission, clinical appointments, colonisation status etc.

Thank you for this comment.

“The research team will also monitor exacerbation rates (participants requiring oral or IV antibiotics during the study period), hospital admission rate and colonisation status.”
 
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