Risk of bias assessment of included studies

As the studies included in this systematic review had different methodological approaches, I used two different RoB assessment tools. While the RoB2 tool was used to assess the methodological

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quality of the three RCTs, the RoBANS tool was used for the five UCBA studies. As the study by Klempel et al. (2013) was considered as a UCBA study as mentioned above, the RoBANS tool was found appropriate for the assessment. Both tools have six categories with different domains.

These are explained below. The RoB assessments including overall bias are summarized in figures which are adapted using RevMan 5.4 software. Graphical summaries of the judgements for each RoB across the studies presented as percentages can be seen from figure 7 and

judgements of RoB for each included study are given in figure 8. When the judgements were similar for both the primary and secondary outcomes, I showed the assessment for both outcomes on a single line. The RoB assessments in more detail for each study can be found in appendix 4.

32 3.2.3.1. Selection bias

In RoB2, selection bias was judged by random sequence generation and allocation concealment, while in RoBANS, it was judged by the selection of participants and confounding variables. For all the studies except the one by Johnson et al., there was low risk of selection bias. There were no baseline differences between different arms of the intervention and no problem with the randomization process and allocation concealment for the RCTs. For the UCBA studies, the participants were adequately selected and appropriate confounding variables were considered.

However, in the study by Johnson et al., some of the variables that might influence the results such as the level of physical activity and duration of stable weight prior to the study were not stated in inclusion/exclusion criteria, hence, there were some concerns regarding this domain.

3.2.3.2. Performance bias

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In RoB2, performance bias was judged by blinding of participants and personnel, while in RoBANS, it was judged by measurement of intervention. In one of the RCTs (20), both the participants and personnel were blinded and participants were not aware of the true aims of the study. However, there was no information about participant blinding in the two RCTs (17, 67). In the study by Cai et al., the study coordinator assigned the participants to the interventions.

Similarly, in all the UCBA studies, participants were aware of the aim, hence, there was a performance bias caused by inadequate measurements of intervention. The reasons that I

considered these as high RoB are, the self-reported methods used in the studies for obtaining the primary outcome of this review and the self-selected eating period in feed days included in the content of the interventions. When participants are not blinded or aware of the true aims of the study, their self-reporting might be influenced and in the self-selected feeding phase, they might choose different types of foods than what they normally consume in order to influence the results, which creates an RoB for both the primary and secondary outcome of this review. In the study conducted by Klempel et al. in 2013, as there is no ad libitum/self-selected feeding period included in the intervention, the RoB of this domain for the secondary outcome was low while RoB for the primary outcome was still high.

3.2.3.3. Detection bias

Detection bias arising from blinding of outcome assessment is a domain in both tools. I found that the RoB of this domain for all the studies was low. The measurement methods for both outcomes are unlikely to be influenced by assessors. Therefore, even when there was an absence of blinding or independency of the outcome assessors, I judged it to have no effect on the

outcome measurements.

3.2.3.4. Attrition bias

Attrition bias arising from incomplete outcome data is a domain in both tools. As it was

important for the judgements of this domain, drop-outs from the intervention arms of the included studies were given with the number, percentage, and reasons in table 9.

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In one of the RCTs (20), although there were considerable drop-outs, these were given with reasons and the allocations of those who withdrew from the study were re-allocated to new participants. Intention-to-treat (ITT) analysis was also conducted, hence, the RoB was low. In the study by Bhutani et al., RoB was high because of the high drop-out rate. In the study by Cai et al., although the drop-out rate was acceptable, baseline characteristics for drop-outs were not given and there was no ITT analysis. Hence, there were some concerns in this domain for RoB. For the UCBA studies, the reasons for drop-outs were given in all studies. For the study by Klempel et al.

(2010), the reasons were collected from the original study. Baseline characteristics for drop-outs were not given, with an exception of one study (68). In the study conducted by Johnson et al., the baseline characteristics were neither given for the drop-outs nor the completers. The RoB for this domain was high in four UCBA studies with high drop-out rates (33, 54, 68, 70). For the other UCBA study with a moderate drop-out rate, there were some concerns for RoB (69).

3.2.3.5. Reporting bias

Reporting bias was a domain common in both tools. In the study by Cai et al., the baseline values for the primary outcome were not given, however, the change from baseline to post-intervention

Table 9. Drop-outs From the Intervention Arms of Included Studies

Study ID: Number of Drop-outs Percentage of Drop-outs Drop-out Reasons

Beaulieu et al. 2019

6 25% Issue with foods or meal plan n=5

Personal reasons n=1 Cai et al.

2019

5 5.3% Could not adhere to diet n=2

Scheduling conflicts n=3 Bhutani et

al. 2013

9 36% Could not adhere to diet: n=3

Scheduling conflicts: n=6 Kalam et

First 3 months: 32.7%

Last 3 months: 11.4%

Disliked diet n=6 (Months 0-3 n=5, Months 4-6 n=1) Scheduling conflicts n=2 (Months 0-3 n=1, Months 4-6 n=1)

Unrelated medical issues n=2 (Months 0-3) Unable to contact n=11 (Months 0-3 n=9, Months 4-6 n=2) Hoddy et

al. 2016

15 20.3% Dietary issues (eg. dislike of foods provided on fast days) n=6 Scheduling conflicts n=2

Personal reasons n=4 Unspecified reasons n=3 Klempel

Inability to follow protocol n=2 (ADF-HF n=1, ADF-LF n=1) Scheduling conflicts n=1 (ADF-HF)

Klempel et al. 2010

4 20% Inability to adhere to protocol n=2

Time constraints n=2 Johnson

et al. 2006

5 35.7% Decided not to continue n=1

Non-compliant with the regimen n=1 Change in vacation plans n=1

Work-related travel n=1

Died of unknown causes during baseline measurements n=1

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was stated in the text. There were no selective outcome reporting and all the results for both the outcomes were present in all the studies, therefore, I assessed the RoB as low for all the included studies.

3.2.3.6. Other bias

I did not identify any other bias in the included studies. However, although these are not related to the methodological quality, I believe that it is important to mention some contradictions or errors in the data of some of the included studies. In the study by Cai et al., although it was not related to the outcomes of this review, there was a contradiction in the sex data in baseline

characteristics. Also, the results given for body weight change in the text, and data given for body weight in the table do not match for both the control and ADF group. In the study by Bhutani et al., although it was not related to the outcomes of this review, there was a contradiction about the duration of controlled and self-selected feeding periods. It was written that there were four weeks controlled and eight weeks self-selected feeding phase, however, they have also stated that the controlled feeding period was from week 1 to 4 while the self-selected feeding period was from week 8 to 12. In the study by Johnson et al., it is not specified whether the data were reported with SD or SEM and for the body weight change, the value for significance was not stated. Two studies had typographical errors (20, 33). In the study conducted by Beaulieu et al., the decrease in hunger from baseline to follow-up in pp analysis was presented without the negativeness in the value, however, the correct value can be seen when checking the given confidence interval in the article. In the study by Hoddy et al., the area under curve (AUC) values for appetite-related outcomes were lacking the last digits of the calculation, however, values can be calculated from the given figures.

3.2.3.7. Overall bias

Overall RoB for the study conducted by Beaulieu et al. was low for both outcomes. Overall RoB for the other studies, except the study by Klempel et al. (2013), was high with all having a high RoB in at least one domain for both outcomes. The study by Klempel et al. (2013), had high RoB overall for the primary outcome of this review, with high risk in one domain, and it had some concerns overall for the review‘s secondary outcome with having some concerns in one domain.