Editor Comments:
1. There is no need to place a comma between the authors’ name and the phrase “et
al.”. For example, lines 73, 84, 95, 107, and 108.
Thank you for identifying this, we have amended these issues throughout the doucment.
2. Lines 178 – 181. These two sentences were written in the past tense. I have the
impression that they will sound better if written in the future tense.
We have amended this section and now reads in future tense.
3. The date for database search should be updated to a date close to when the study
protocol will be submitted.
We appreciate the desire to have an up to date search. As this is projected to be
a large review (i.e. a large number of articles eligible for inclusion) we were proposing
that no further updates of the search beyond the date that we originally indicated
would occur. However, we can also see benefit of ensuring the search is as up to date
as possible. Therefore, we will update the search on 1st of December, 2021 and not
conduct any further search updates to ensure the search is reproducible. This has
been added in the manuscript on Page 10, Lines 215-216 (of the unmarked manuscript).
Reviewer One:
Overall, the manuscript is well written and designed. To determine if the interaction
of individual training variables to derive RT dose, dosing, and dosage can influence
muscle strength and determine if an optimal prescription range exists for developing
muscle strength. But I have some questions that I think are important to be answered.
Thank you for this positive outlook of our study design. We have responded to specific
questions below.
1. An interesting series of secondary analyzes were suggested, but did you also consider
comparing the responses of men and women?
Thank you for this suggestion. We are anticipating many studies that will be eligible
for inclusion in this systematic review and meta-analysis. As such we have included
in the secondary analyses that dose-response effects between males and females will
be assessed if sufficient data is available.
Page 16, Lines 323-326:
“After the primary analyses have been completed, a series of sub-analyses will be
conducted, if possible, to examine the effect of age (young vs. middle-aged vs. elderly),
sex (male vs. female), training status (trained vs. untrained), and assessed body
musculature (lower vs. upper-body) on muscle strength adaptation following RT.”
2. Among the outcomes described is Muscle Morphology. Do you intend to evaluate Muscle
Morphology? Because the direction of the entire manuscript suggests that only Muscle
Strength will be evaluated. If they intend to evaluate Muscle Morphology, the manuscript
needs to make this clearer.
We do not intend to evaluate muscle morphology, this term was used in the PICO (Table
1) “outcomes” which do not depict the outcomes proposed for this study. This outcome
was included in the search strategy as studies examining muscle morphology may also
evaluate muscle strength despite it not being a primary outcome. As such, this may
lead to additional eligible studies that would be included in our systematic review
and meta-analysis. As a result, no change has been made to the manuscript.
3. I suggest using the GRADE tool (Grading of Recommendations Assessment, Development
and Evaluation) to evaluate levels of evidence for each of the analyzes you intend
to do.
It may have been missed by the reviewer that we had stated in the manuscript under
the subheading “Assessment of Methodological and Outcome Quality (Risk of Bias)” that
quality of outcomes will be evaluated using the GRADE tool. The quality of individual
studies included in the review and to assist with formulating GRADE outcomes will
be determined by Pedro and Testex. To improve the clarity of this section and not
to inadvertantly reduce the emphasis of the quality of outcomes, we have removed “(Risk
of Bias)” from the sub-heading. This subheading now reads as:
“ Assessment of Methodological and Outcome Quality” and can be found on Page 13, Line
255.
4. The PROSPERO record number is in the abstract, please also add it in the text body.
When we originally submitted the protocol manuscript, we had submitted the protocol
for registration with PROSPERO. Since then, PROSPERO identified that we were not investigating
a clinical population and therefore decided to cancel the registration. To clarify,
the methods presented in this manuscript were not identified as an issue, only that
we were not investigating a clinical population. Our protocol has since been registered
with The Open Science Framework (OSF). The information has been revised in the abstract
and included in the methods.
Page 2, Line 18-19:
“(doi.org/10.17605/OSF.IO/EH94V) systematic review with meta-analysis...”
Page 10, Line 205-206:
“This systematic review protocol has been prospectively registered with Open Science
Framework (OSF),[51]...”
Please add information suggested in the Plos One submission guideline:
5. Where and when the data will be made available. See our Data Availability policy
for more.
There is no underlying data available to share for this protocol paper. Therefore,
at this time we can not share any data. Any data generated as a result of this review
is intended to be published via FigShare. The location of this data will be made available
when they have been fully curated and the findings are published.
Page 14, Lines 288-289:
“The extracted data will be published and freely accessible via FigShare after the
data have been fully curated and published.”
6. A completed PRISMA-P checklist must be provided as a supporting information (SI)
file. See PRISMA-P Explanation and Elaboration for more information on completing
your checklist.
We believe in being open and transparent in science. In our initial submission we
included a PRISMA-P checklist but we have referred the reader to this now in the manuscript.
Page 10, Lines 205-208:
“This systematic review protocol has been prospectively registered with Open Science
Framework (OSF),[51] and is reported in accordance with the preferred reporting items
for systematic reviews and meta-analyses protocol (PRISMA-P) guidelines (supplementary
file 1).[52]”
Reviewer Two:
Dear editor, the authors of the study in question propose to carry out a systematic
review with meta-analysis to understand the effect of the interaction between the
variables volume (series x repetitions x number of exercises) x intensity: dose; volume
x intensity x frequency: dosing; volume x intensity x frequency x duration: dosage;
in the maximum dynamics strength response after a resistance traning. A second objective
would be to indicate an optimal prescription for increasing strength based on the
results of these interaction.
1. There are already studies (i.e., systematic reviews) that individually analyzed
intensity, volume, frequency and duration, and quite few studies that have analyzed
the interaction of variables in the strength response. The reason to conduct a study
should not be by the number of studies available in a determined theme, but by the
reasoning, whether in biomechanics, physiology or any other field, which allows sustaining
the study hyphothisis, and further the execution of a study.
We agree with the reviewer in that there have been systematic reviews that have analysed
individual variables of resistance exercise prescription and some that have tried
to consider their interaction. However, in all of the reviews that we are aware of,
they have categorised the variables and compared one category to another. In the systematic
review by Borde et al. the authors noted that it was not possible to consider how
the variables interacted. In this review, we are proposing the most comprehensive
approach to integrating variables that we can identify. We are also proposing not
to simply compare groups or categories of exercise prescription but to conduct a dose-response
analysis using two continuous variables using an approach that has recently become
available. Most dose-resonse analyses use a categorical and continuous variable. Although
this does not specifically provide biomechanical or physiological reason, we have
added some text throughout the introduction to provide an overview of the possible
neurophysiological responses that might contribute to increased strength, noting that
the mechanisms of increasing strength are still debated.
2. The present study does not present any neurophysiological basis that justifies
the combined analysis of the variables mentioned in order to increase maximum strength,
and contribute to a more assertive prescription. In addition, the reason for performing
three analyses: dose, dosage and dosage instead one, two or even more, was not discussed.
It would be interesting to clarify the advantages of each analysis. Also, the Prospero
ID (ID number: 1922649) was not found (https://www.crd.york.ac.uk/prospero/) as announced.
We have added some text throughout the introduction to provide some possible neurophysiological
mechanism to contribute to increased muscle strength. Although this on its own probably
is not sufficient to satisfy this reviewer, we have also identified in the introduction
that the neurophysiological mechanisms for increasing muscle strength are still being
debated. It is important to note though, that this review nor other reviews, is designed
to identify potential mechanisms of increased strength, but to see if the strength
response is magnified when the resistance training prescription variables are considered
as a whole. While it is important to consider and hypthosise about potential mechanisms
and reasons for why there might be an interaction of variables (which we have now
included), we think it is just as important to determine if the variables interact.
If the finding indicates that interaction is occuring, further research on mechanisms
can then be undertaken.
The reason for conducting the series of meta-analytical dose-response functions is
to systematically add individual variables to the interaction and observe if the dose-response
function changes. This will assist in determining if there is any one or a combination
of variables that contribute most to the increased muscle strength that is a known
outcome associated with resistance training. Although we are not aware of a statistical
approach that will allow for the dose-response functions to be statistically compared,
it will be possible to plot the curves from each meta-analysis on the same axes to
demonstrate if any magnification in response is occuring.
The Prospero ID was registered. However, since the original submission of this protocol
manuscript Prospero re-examined the registration and identified that no clinical population
was being examined and therefore it was not suitable for registration with Prospero.
Importantly Prospero did not raise concerns about the method, simply stating that
the population was not appropriate to register the work with Prospero. We have now
registered the protocol with open science framework (OSF) and as noted in response
to Reviewer one, included this in both the abstract and the methods.
Page 2, Lines 18-19:
“(doi.org/10.17605/OSF.IO/EH94V) systematic review with meta-analysis...”
Page 10, Lines 205-206:
“This systematic review protocol has been prospectively registered with Open Science
Framework (OSF),[51]...”
3. The basis for investigating either interaction is weak and requires additional
information. To illustrate, the authors used more than one page in the introduction
to conceptualize the variables. This approach is necessary, but brief, being important
to substantiate/hypothesize why and how the interaction of these variables allows
for a greater increase in the strength production after an intervention.
We have added some text to the introduction to strengthen the rationale, specifically
trying to address potential neurophysiological mechanisms. However, the evidence for
mechanisms to increase muscle strength as a result of resistance training are equivocal.
We have tried to clarify other elements relating to the points above from this reviewer
and believe that there is now a strong rationale depicted for taking this approach.
4. The authors proprose to review studies without target subject or body members (upper
or lower), where the main inclusion criteria was the maximum dynamic strength been
evaluated before and after an intervention from three databases (CINAHL, MEDLINE,
and SPORTDiscus). This give me the impression of unfeasibility due to the extensive
number of studies. I believe that without a direction (i.e upper limbs or any specific
exercise or even population) this project is unlikely to be carried out.
The reviewers concern is noted. However, I would encourage the reviewer not to judge
feasibility without knowing the extent of the research team or any resources that
might be at our disposal. We agree that not specifying a target population or specific
body area will result in a very large search result. However, to be able to calculate
an accurate dose-response, it is critical to have a large data set. We fully expect
to have a much larger number of eligible articles than is typically identified from
a more specified and refined search, but fully believe that we have capacity to complete
this review. It is also partly the purpose for publishing the review protocol, to
demonstrate our committment to completing this and acknowledging that the findings
might take longer to arrive at and publish than a typical systematic review might.
5. Greater statistical detail is necessary, as it lacks information to explain how
the data will be treated to answer the study questions, and achieving the objectives
proposed.
As recommended, we have elaborated further on our statistical methods. The following
has been added to the manuscript.
Page 2, Lines 33-35:
“Meta regressions will investigate between-study variances and a funnel plot and Egger’s
test will assess publication bias”
Page 15, Lines 302-306:
“The main study outcome measure will be the standardised mean difference (SMD) in
muscle strength estimated as the mean difference of the cases and controls divided
by the standard deviation of the overall population in the study. The pooled standardised
mean differences (SMD) of the extracted muscle strength data (continuous outcome measure)
will be estimated using the DerSimonian and Laird random effects method [59].”
Page 16, Lines 316-322:
“Random effect models also assist in controlling for unobserved heterogeneity when
the heterogeneity is contact over time and not correlated with independent variables.[59]
Meta regressions will be constructed to investigate and quantify the proportion of
between-study variance explained by known study variables including age, sex, training
status, body musculature, muscle strength adaptations and risk of bias. Publication
bias will be assessed using funnel plots and Egger’s tests. Asymmetry will be considered
if the P < 0.10 for Egger’s test, indicating potential publication bias.[61]”
Page 16, Lines 326-327:
“Sensitivity analyses will be conducted by risk of bias, in which the analyses will
be re-run while excluding poor quality studies.”
In addition, we have added a new subheading “Data Treatment” which can be found on
Pages 14-15, Lines 290-300, and reads as:
“Data pertaining to resistance training variables extracted as described, will be
subjected to several treatment approaches to derive the proposed composite values
of dose, dosing, and dosage. The specific exercise prescribed in each study will be
identified and the relevant number of sets and repetitions will be recorded, along
with the prescribed intensity (load). For each exercise, the number of sets, number
of repetitions and prescribed intensity will be multiplied to derive the volume of
work for each specific exercise. Following this, the volume of work for each specific
exercise will be summed to derive the training dose. Once the training dose is derived,
this will be multiplied by the weekly training frequency to derive dosing. The dosing
will be multiplied by the training duration (weeks) to derive dosage. If sufficient
data is not available for each data treatment stage, the article will be excluded
from subsequent analyses.”
6. In the discussion it is said that the results can be the key to a prescription
of a defined variable or by combination. However, other important variables were left
out, for example: range of motion and pause. I believe that the text should be a little
more conservative and direct the discussion by the possible results found and not
extrapolate in the sense of formulating an ideal prescription based only on the investigated
variables.
It is indeed possible that other variables that we are not considering in this review
could contribute to the development of strength. However, the evidence for the importance
of these variables and how to use them in prescription is still being developed. For
this reason we don’t beleive that these additional variables can be quantified as
part of an interaction of variables to create a composite outcome. Despite not including
these variables, we have changed the discussion to be more conservative about the
potential outcomes of this review by specifying the training variables investigated.
7. For all the above aspects, I believe that the article is not fit for publication.
Other information is provided in the attached document, addressed to the authors.
In responding to the above aspects and providing additional rationale we hope that
you now believe the manuscript of our review protocol to be fit for publication. Additional
evidence of this is provided by responding to the below comments and associated changes
to the manuscript. We strongly believe that further consideration of how individual
variables interact is important to see if it is possible to simply modify a single
variable or if multiple variables should be manipulated in unison to encourage muscle
strength development.
8. Dear authors, below are my comments. In opinion the work needs major improvement
and should not continuing in the review. The work is well written, but the foundation
for the execution/reproducibility of the project is little sustaintable. It would
be interesting if the authors presented minimal mechanistic bases to justify the analysis
of the interaction of variables. There are several studies that analyzed each of the
variables in isolation, so why would it be necessary to carry out a combined analysis?
What supports this analysis? And why should it be done from the perspective of dose,
dosing, and dosage? What each of these analyzes contribute to the training prescription?
To illustrate, the authors used more than one page in the introduction to conceptualize
the variables (Ln 80-137). This approach is necessary, but brief, being important
to substantiate/hypothesize why and how the interaction of these variables allows
for a greater increase in strength production after an intervention.
Thank you for the positive comment relating to the writing. We appreciate the reviewers
concern around the mechanistic bases, and as previously outlined, have added elements
of this throughout the introduction to identify that different variables could be
inducing strength changes through various mechanism, and it is unclear if these are
additive. Although we considered taking a briefer approach to the introduciton, we
felt it important to clearly outline and define each of the variables of interest
(while acknowledging the potential role of other variables) and describing the potential
related mechanisms. Therefore the introduction has been expanded.
9. It would be interesting to clarify which are the dependent and independent variables
of the study and how the statistical procedures will contribute to the establishment
of dose, dosage, and dosage. Finally, I think you should have a specific group for
the analysis (adult, non-trainined, trained, atlhetes etc) or a region of the body,
or even a specific exercise. The work is very wide and without a direction it may
be unlikely to be carried out.
We have responded to the statistical approach below and made changes in the manuscript.
We also address the thought about delimiting the search to the specific comment below,
but in this instance of attempting to compute the dose-response function, do not believe
this to be appropriate. The size of the expected work should not be considered as
a reason for it being unlikely to be carried out. As we have and will indicate, part
of the purpose for publishing this protocol is to highlight that we are completing
this project, provide the clear protocol that we will be following and to maintain
accountability for completing the project. Noting that the time that it takes to complete
the project and publish the findings is likely to be greater than one would traditionally
expect with a tightly controlled and specified systematic review and meta-analysis.
10. Title: The terms dose, dosing, and dosage are confusing, and only explained along
the text. I suggest not leaving them in the title.
As suggested, we have amended the title to “The influence of considering individual
resistance training variables as a whole on muscle strength: A systematic review and
meta-analysis protocol”.
11. Ln 38. You wrote sets x repetitions. I think you would like to say: number of
sets x number of repetition. Please clarify.
It appears that this question is specifically for Ln 28. We have amended the abstract
as suggested. This now reads as:
Page 2, Lines 21-24:
“To derive RT dose, the following calculation will be implemented: number of sets
× number of repetitions × number of exercise × intensity, while RT dosing factors
in frequency and RT dosage considers program duration.”
12. Ln. 24. I did not find the Propero ID (https://www.crd.york.ac.uk/prospero/) by the number provided.
When we originally submitted the protocol manuscript, we had submitted the protocol
for registration with PROSPERO. Since then, PROSPERO identified that we were not investigating
a clinical population and therefore decided to cancel the registration, . To clarify,
the methods presented in this manuscript were not identified as an issue, only that
we were not investigating a clinical population. Our protocol has since been registered
with The Open Science Framework (OSF). The information has been revised in the abstract
and methods.
Page 2, Lines 18-19:
“(doi.org/10.17605/OSF.IO/EH94V) systematic review with meta-analysis...”
Page 10, Line 205-206:
“This systematic review protocol has been prospectively registered with Open Science
Framework (OSF),[51]...”
13. Ln 30 The word style seems to be different.
We have checked the manuscript to correct any differences in font size or style and
do not believe any differences remain.
14. Ln 33. The pooled standardised mean differences of what?
As suggested we have amended the sentence to the following:
Page 2, Lines 28-29:
“The pooled standardised mean differences for muscle strength will be estimated using
DerSimonian and Laird random effects method.”
15. Ln 34-37. It is necessary to describy what are you comparing.
We have clarified what we are comparing in the proposed systematic review and meta-analysis.
This now reads as:
Page 2, Lines 29-33:
“Linear and non-linear dose-response relationships will be estimated by fitting fixed
effects and random effects models using the one-stage approach to evaluate if there
is a relationship between exercise dose, dosing and dosage and the effect on muscle
strength. Maximised log-likelihood and the Akaike Information Criteria will be used
to compare alternative best fitting models.”
16. Ln 37-39. Why do you think the proposed variables are enough to compose the best
prespriction for strength increase? Previous studies indicated the strength increase
is specific to the range of motion training (https://pubmed.ncbi.nlm.nih.gov/23604798/; https://pubmed.ncbi.nlm.nih.gov/33977835/; https://pubmed.ncbi.nlm.nih.gov/31230110/). However, nothing is said about the range of motion. If the strength increase is
dependent of the range of motion trained, why this variable was not include or even
mentioned?
The descision to incorporate the number of sets, the number of repetitions, intensity,
frequency, and duration is due to the already established guidelines. We believe that
taking into account the above variables will provide an accurate account of the total
dose, dosing, and dosage of a resistance training program, as these variables can
be quantified in both relative (arbitary units) and absolute (kilograms or pounds)
terms. For other variables like range of motion; which indeed has shown to influence
muscle strength, further investigation is needed to determine how muscle strength
is impacted throughout the various ranges of motion for each exercise and muscle group.
Although research suggests that range of motion is important, all possible ranges
have not yet been identified and it is not clear if or how this effects the total
volume of work. On this basis, we do not believe that including range of motion in
the dose calculations for this study will add substantial benefit. Furthmore, the
method in which range of motion is assessed is often approximated using a goniometer
or visual observation. It is also reliant on the participant being consistent with
their range of motion for each repetition throughout the intervention, and that the
researcher can assure that the range of motion has been adhered to throughout the
intervention. If range of motion was incorporated as one of the variables for dose
calculations, it is likely that few studies would provide the specific range of motion
for each exercise. Consequently, this would mean that a study would not be quantifiable
and therfore excluded from the meta-analysis; severely limiting the available data
and potentially calculating a dose-response effect unlikely. Furthermore, it is hoped
that the application of these equations can be easily used within practical settings.
As such, we believe that including range of motion as one of the variables in the
equation would not be practical for most health and fitness professionals.
However, we appreciate that there are variables that we have not considered and have
added text to identify that we have selected variables based only on those recommended
and outlined in resistance training guidelines. We have also added text that identifies
the potential role of other variables (including range of motion). We have amended
the text to be more conservative about how the findings might be used.
17. Ln 51.” Resistance training guidelines have been developed to guide”: repetitve
terms.
We have amended this sentence to the following:
Page 3, Lines 45-46:
“Resistance training guidelines have been developed to direct the attainment of muscle
strength, hypertrophy, and power.[6, 7]”
18. Ln 55. why the other variables were not cited?
Thank you for identifying this, this appears to be an issue with EndNote. This has
now been corrected, and we have also included repetition cadence in the variables.
19. Ln 56. The reference cited only informs about volume and intensity. What about
the other variables mentioned? They shoud be covered by other references.
As addressed in response to comment 17, we have added additional references for the
other variables, and included repetition cadence. Please see Page 3, Line 50.
Page 3, Lines 46-50.
“These guidelines have been adapted for individuals across the lifespan, from children
to older adults,[8-11] and encompass the manipulation of training variables; exercise
selection and order, repetition cadence, range of motion, rest intervals, weight load,
frequency, sets and repetitions, to specifically stimulate mechanical and metabolic
stress.[12-18]”
20. Ln 56-58. You present a problem that you are not able to solve by the analysis
offered, as this prescription requires the analysis of other variables such as execution
speed, range of motion and pause. I recommend you be more conservative.
We understand that range of motion and pause, as well as repetition cadence are important
variables in exercise prescription. However, at this point do not believe that there
are accurate quantification methods being utilised and it is unclear how these would
contribute to training volume. As previously addressed, we believe that range of motion
should not be included in the dose calculation and that range of motion is often assessed
as an approximation and not utilising a machine or exercise that has in place the
specific range of motion being investigated. In addition, if range of motion was incorporated
as one of the variables for dose calculations, it is likely that few studies would
provide the specific range of motion for each exercise, which may severely limit the
data necessary to calculate a dose-response effect. With regards to execution speed,
or what is better known as repetition cadence, we believe that this is a variable
that can be quantified to some extent. We have not included this variable in the proposed
dose calculations as studies that specify a particular repetition cadence often don’t
specify if this cadence was performed for all exercises, and if this cadence was performed
during maximal strength testing, hence questioning the validity of measurement. If
the maximal strength test was not performed at the specified repetition cadence, then
it is possible that the maximal strength would not accurately reflect the relative
intensity of the exercise prescription, and consequently impacting the total dose
calculations. In addition, although repetition cadence can be quantified in seconds,
the contributions of concentric and eccentric loading to volume are presently unquantifiable.
Again we have identified that we are not considering all possible training variables
and have amended the text to be more conservative in our possible explanations and
uses. Further we have refined the statement of the problem to.
Page 3, Lines 56-59:
“It is not yet known how these specific variables (sets, repetitions, intensity, frequency,
and duration of a program) contribute to the total dose of RT as their interaction
has not yet been determined.”
21. Ln 66 You describe a problem (which variable is most important for maximal strength
increase...) that you won't be able to answer. I suggest rephrasing the sentence.
The sentence specifies that based on the literature, there is no clear resistance
training variable that is responsible for muscle strength development. We then expand
and propose that there may not be a single variable that is primarily responsible,
but rather a combination of variables. We have clarified in the manuscript the specific
variables that are being referred to as not all training variables can be investigated.
This sentence has been rephrased to the following.
Please see Page 4, Lines 67-70:
“Therefore, it remains unclear whether a specific training variable (e.g. the number
of sets, the number of repetitions, intensity, frequency, or duration) is more important
than another, or if the interaction of variables results in larger muscle strength
adaptations.”
22. Ln 71-73. The analysis of volume x intensity allows to understand the dose of
the training section. The analysis of volume x intensity x frequency allows us to
understand the weekly dose, but the analysis of these variables with duration would
allow which interpretation? nothing was said about it?
As suggested, we have amended this section, and is as follows.
Page 4, Lines 71-77:
“There are three potential ways in which the variables are likely to interact with
one another; 1) RT dose considers the interaction of RT volume (number of sets x number
of repetitions x number of exercises) and intensity, allowing an individual RT session
to be considered; 2) RT dosing considers the interaction between RT volume, intensity,
and frequency, allowing a week of RT sessions to be considered; and 3) RT dosage considers
the interactions between RT volume, intensity, frequency, and the duration of the
program intervention, allowing all RT sessions throughout the intervention period
to be considered.[28, 29]”
23. Ln 76. “must consider the duration of a program”. Why? Please, you need to clarify
these issue. What about other variable that were left out, such as workload? (https://pubmed.ncbi.nlm.nih.gov/21113614/)
Workload is often calculated as: sets × repetitions × intensity, however different
studies have clarified this term differently. Often in literature it is not clarified
if the workload calculated is for all exercises prescribed in the intervention or
for the exercises where maximal strength is being assessed. In this manuscript, we
propose that resistance training dose should be calculated as: the number of sets
× the number of repetitions × the number of exercises × intensity. This incorporates
the calculation of ‘workload’ while providing clarity on the number of exercises the
calculation is referring to. It is important to note that this calculation only considers
the potential effect of a single resistance training session, and that in exercise
prescription multiple training sessions are performed per week and can continue for
many weeks, months, and years. As such, when the frequency (the number of sessions
per week) is considered, this calculation considers the potential effect of resistance
training over the course of a single week. When the duration (the number of weeks
the intervention lasts) is considered, this calculation considers the potential effect
of the whole resistance training program. We appreciate the comment and have clarified
why resistance training duration should be considered, we hope this is suitable. The
amendment is provided below.
Page 4, Lines 77-80:
“Although Price et al.[29] considered the number of sets, repetitions, load, and frequency
in their evaluation of RT dosage, this fails to consider the duration of a program
which would incorporate all training sessions from the beginning until the end of
an intervention. “
24. Ln 80 a 137. The concepts of each variable could have been summarized in two paragraphs,
and then, the reasoning of the neurophysiological mechanisms that support the importance
of analyzing the interaction of the variables presented in the force response could
have been presented.
We agree that the concepts of each variable could have been summarised in two paragraphs,
however we feel that the expanded overview of each is necessary to define the variables
and potential interaction around dose, dosage and dosing. However, we also agree that
the neurophysiological mechanisms that might support the interaction of variables
was overlooked in this approach. Therefore, we have chosen to integrate the potential
mechanisms for each variable rather than presenting a separate section on the mechanisms.
Partly this is because the mechanisms of increased muscle strength remain inconclusive
and difficult to define. We hope that this approach satisfies the reviewer.
25. Ln 111. “It is also important to consider the influence of RT frequency and duration”
. Why it is importante to consider? Please clarify
To be more concise we have removed this sentence as it did not add any additional
material to this manuscript. The importance of considering RT frequency and duration
is described in the following section of the manuscript, which can be found on Pages
6-8, Lines 128-164.
26. Ln 115-117. No reference was given.
We apologise for missing this. A reference has now been added. Please see Page 6 Line
130.
27. Ln 122. It is important to metion that it is account only for the same muscle
group.
We have corrected this, and specified that the resistance training frequency was recommended
for individual muscle groups. This sentence has been amended.
Page 7, Lines 135-138:
“This RT frequency has been reaffirmed by Feigenbaum et al.[7] who recommend a 48
hour rest between concurrent training sessions, which corresponds to three training
sessions per week for individual muscle groups.”
28. Ln 135-137. Little information was given to “Duration” compared to the other variables.
The information around “duration” is limited but reflects the amount of research that
has been conducted on this topic. To the best of our knowledge, no original research
study or systematic review and meta-analyses has specifically attempted to investigate
the influence of resistance training program duration on muscle strength. Within resistance
training guidelines, there is also no recommendation for program duration. This is
possibly due to training being recommended to be life-long. However, this is a training
variable that could contribute to strength development particularly in specific populations
(i.e. untrained). While it could be considered that the program duration should be
4-6 weeks to be in line with broad recommendations about when overload should be applied,
there is no good quality evidence to support this.
Inadvertently this variable has been examined through the re-testing of maximal strength
throughout an intervention, with strength seemingly plateauing as duration is extended,
but limitations in the study design used do not enable conclusive interpretations.
As resistance training programs can vary widely from publication to publication either
through sample size, population characteristics, program intervention, and study design,
etc., it is not yet possible to transfer results from single or small numbers of studies
into real-world applications. We have added some text to highlight this in the manuscript
(Pages 7-8 Lines 151-164).
29. Ln 149. The question presented has not yet been answered and will not be answered
by the study. I see no justification for your permanence. Perhaps present a question
closer to the question you want to answer.
Although the question posed is an appropriate question, on reflection we recognise
the challenges with being able to conclusively answer that question. We have amended
the problem question to the following.
Page 9, Lines 180-181:
“Does the interaction of specific resistance training variables to quantify the amount
of training completed influence the dose-response function for muscle strength.“
We feel that this question better reflects the studies proposed aims, and that this
question can be answered with the study design we propose.
30. Ln 154-158. Please clarify how the dose, dosing and dosage could influence the
development of muscle strength.
It is plausible that the interaction of different resistance training variables in
the form of dose, dosing and dosage will positively combine neurophysiological mechanisms
for the development of muscle strength to lead to larger effects. We have added some
text to highlight the potential mechanisms that could be induced might be summative
and lead to a positive interaction with larger (magnified) dose-responses.
Page 9, Lines 189-199
“It is important to delineate how the dose (number of sets × number of repetitions
× number of exercises × intensity), dosing (sets × repetitions × exercises × intensity
× frequency) and dosage (sets × repetitions × number of exercises × intensity × frequency
× duration) influences the development of muscle strength, and if a primary driver
of this outcome can be identified. These combinations of variables have the potential
to induce different neurophysiological mechanisms including motor unit recruitment
and firing, motor learning (specific fibre types), agonist-antagonist co-activation,
metabolic stress, and increased cross-sectional area. However, it is unknown if these
variables and potential mechanisms indeed interact or are summative to induce larger
increases in muscle strength. Given that changes in training volume, training intensity
and intervention duration have been identified as important factors by Borde et al.[50]
and are likely to induce different mechanisms…”
31. Ln 174. “All” articles prior to july 2021? I think you should delimitated a specific
group (i.e., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4656698/), or a body member, or an specific exercise.
We understand and appreciate the reviewers concern about the size of this review,
however we believe that it is appropriate not to delimit the search in this instance
to ensure that a large enough sample is available to generate an accurate dose response
curve. Although we anticipate a high volume of articles, we believe that it is necessary
to encapsulate as many manuscripts as possible. We chose not to delimit to a specific
population because there is no good evidence to support variation in muscle strength
development between populations and we are interested in assessing if the resistance
exercise dose, dosing, or dosage required to stimulate muscle strength changes with
factors like age. These additional variables can be included in analyses as co-variates
and specifically investigated in sub-analyses. Depending on the number of studies,
there might be the opportunity to conduct sub-anlyses to see if the dose-response
curve is different for specific populations. We chose not to deliminate the whole-body
because we believe that this would impact the practical application of our data. For
example, the prescription of split upper- and lower-body resistance exercise is common
in experienced lifters, however, is not often prescribed for untrained populations.
We did not want to deliminate a specific exercise as we believe this would severely
limit the data that would be eligible for extraction, this would be particularly evident
in studies that include multiple exercises. Further, this would impact the calculation
of resistance training dose, as the calculation considers the number of exercises.
We understand that the approach that will be undertaken will result in many studies,
but we believe that it is necessary to answer questions and we have a specific research
team working on this to ensure that it is achievable. In response to the editor also
wanting the search to be the most up-to-date as possible, we have made a decision
to search up until 1st December 2021. Please see Page 10, Lines 215-216.
32. Ln 178. Which groups?
This sentence was describing the fact that we were considering non-exercise comparators
to be able to calculate the size of effect to be considered in the dose-response analysis.
We appreciate that this wasn’t expressed as clearly as it could have been. We have
made some adjustments to make this clearer.
Page 11 Lines 221-225:
“Muscle strength data from eligible intervention groups will be compared with data
from individuals receiving no exercise intervention or a placebo exercise intervention
(i.e. stretching and/or mobility exercise) not designed to improve strength. Aerobic
exercise only interventions have not been considered appropriate as a comparator to
exclude any potential strength benefits from this mode of training, particularly in
exercise-naïve populations.”
33. Ln 235. Please, give an example for better understanding. Why the median and not
the mean?
For the purpose of consistency between extracting data, we believe that extracting
the median is more appropriate given that intensity can widely range in exercise prescription
(e.g. 20%1RM to 100%1RM). From a provided range, it is not appropriate to calculate
the mean since the mean is determined from a series of exact values. Hence the decision
to use the median (central value). In most instances, we think the mean and median
would provide essentially the same value. We also acknowledge that the progression
of intensity over long durations will vary and may not be normally distributed. Moreover,
the duration of intensity prescription may not be normally distributed over the course
of an intervention. For instance, participants are prescribed 40%1RM for 2-weeks,
followed by 4-weeks at 60%1RM, 8-weeks at 80%1RM, and 3-weeks at 90%1RM. Therefore,
if the mean was used instead of the median, it is possible that intensity could be
under- or over-estimated. The median on the other hand provides the central tendency
for skewed number distribution, which given the previous example, would provide a
more accurate account of intensity. While we acknowledge that either approach is likely
to contain some degree of error, we feel that the most appropriate approach is to
determine the median.
We have provided an explanation why we have chosen the median, as the mean is often
reported in literature. The followed was added to the manuscript.
Page 14, Lines 273-277:
“The median was chosen as wide ranges in resistance training intensity (i.e. 20% 1RM
to 100%1RM) can be applied, along with variation in how it is progressed throughout
an intervention. If the mean was to be used instead of the median, it is possible
that intensity could be under- or over-estimated. Utilising the median will provide
the central tendency for skewed number distribution.”
34. Ln 245-248. Why 10%? What is the rationale for this procedure?
We are anticipating that this study will identify hundreds of eligible articles for
data extraction. Although it is recommended by Cochrane that data are extracted independently
by more than one person, it is also rare for systematic reviews to include the number
of articles that we are expecting. Therefore, we have made a pragmatic decision to
check accuracy of a single data extractor initially in 10% of included articles. As
this is a process to ensure integrity of data, if there is any variation in data extraction
outcomes, data from all articles will be completed independently by two investigators.
35. Ln 268. No answer is absolute. Each study adds knowledge on the subject and its
contribution cannot be disregarded. Please re-do the sentence.
Our intention certainly was not to disregard any study or findings, but simply to
identify that there are limitations in the evidence and that we are proposing a way
to potentially address some of these limitations. We have amended this sentence and
it now reads as:
Page 16, Lines 331-336:
“Although previous attempts to evaluate the dose-response of individual RT variables
using standardised mean effects have identified key variables of interest, there has
not been a consistent approach to determining the overall dose, dosing and dosage
obtained through the interaction of variables.[50] The approach proposed will utilise
dose as a continuous variable instead of categorising variables/outcomes to identify
if one category is different to another.”
36. Ln 269. “Instead, previous analyses have simply categorised variables/outcomes
to 270 identify if one category is different to another “ . As it is, it gives the
impression that the previous work was reduced and contributed little. I believe that
the phrase could be redone by valuing the previous work and at the same time adding
actions that would complement the previous initiative.
It was not our intention to devalue another authors work. We have amended this section
and further expanded from the above amendment. This now reads as.
Page 16, Lines 331-336:
“ Although previous attempts to evaluate the dose-response of individual RT variables
using standardised mean effects have identified key variables of interest, there has
not been a consistent approach to determining the overall dose, dosing and dosage
obtained through the interaction of variables.[50] The approach proposed will utilise
dose as a continuous variable instead of categorising variables/outcomes to identify
if one category is different to another.”
37. Ln 271-272. You are disregarding the other variables. I think the phrase would
be better if you commented only for the effect of the interaction between the variables
that are being investigated.
We acknowledge that we are not considering all potential variables and this is partly
because it is currently not clear how to best quantify some of these. To address this,
we have amended the sentence to specify the training variables that are being analysed
in the proposed study. This now reads as:
Page 16-17, Lines 336-340:
“By gathering, analysing, and synthesising the information about the number of sets,
number of repetitions, number of exercises, and RT intensity, frequency, and duration
of the RT program on a continuous scale and evaluating if the interaction of these
variables influences muscle strength differently, this study might offer new directions
for practice and future research.”
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