Evidence-Based Guidelines MM
Evidence-Based Guidelines MM
Evidence-Based Guidelines MM
Abstract
Background: Patients with multiple myeloma (MM) are often treated with chemotherapy, radiation, and, if indicated,
autologous stem cell transplant. In addition to side effects of the treatment, patients with MM often have bone pain,
pathological fractures, spinal cord compressions, fatigue, and muscle weakness, which negatively impact functional
performance and quality of life. Currently, there are no related guidelines for safe and effective physiotherapy
(PT) management. Accordingly, the aim of the present study is to develop guidelines for effective physiotherapy
management of patients with MM by systematically reviewing and evaluating the available evidence followed by
a consensus process to specifically describe the research questions as detailed below.
Methods/design: Physiotherapy management guidelines for patients with multiple myeloma will be developed
based on the results of a systematic search of the following databases: US National Library of Medicine Database
(PubMed), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE),
Cumulative Index to Nursing and Allied Health Literature (CINAHL), Elton B. Stephens Co. (EBSCO), Web of Science,
Database of Abstracts of Reviews of Effects (DARE), Cochrane Database of Systematic Review, and Physiotherapy
Evidence Database (PEDro). All articles will be screened for inclusion and exclusion criteria. Relevant potential
articles will be identified and systematically reviewed for final phase of inclusion. Two independent reviewers will
systematically review and analyze the quality of identified articles using standardized assessment tools. Scientific
conclusions will be drawn and recommendations will be made based on a critical appraisal process. The guideline
development will also be based on the team’s judgment about the overall quality of the studies and a
consensus process.
Discussion: Draft guidelines will be developed in the form of action statements based on the strength of
evidence and grades of recommendations. The draft guidelines will be reviewed internally by two independent
reviewers using AGREE II and externally by a methodological expert from Evidence-Based Care – Cancer Care Ontario
and will be sent to the Canadian Physiotherapy Association (CPA) for feedback from physiotherapists.
Systematic review registration: PROSPERO CRD42017064056
Keywords: Multiple myeloma, Physiotherapy, Guidelines
* Correspondence: [email protected]
1
Medicine, Oncology and Palliative Care, Health Sciences North, Sudbury,
Ontario, Canada
2
Northern Ontario School of Medicine, Sudbury, Ontario, Canada
Full list of author information is available at the end of the article
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Jeevanantham et al. Systematic Reviews (2018) 7:118 Page 2 of 8
The recommendations will be sent to the CPA to obtain effort and publication bias [19, 20]. This study will
feedback from physiotherapists. The guidelines will also be adhere to the Preferred Reporting Items for Systematic
reviewed by a methodological expert from Evidence-Based Reviews and Meta-analyses Protocol (PRISMA – P 2015)
Care - Cancer Care Ontario. checklist. The PRISMA – P 2015 checklist is comprised of
17 items, categorized into administrative information,
Development of research questions introduction, and methods [21, 22]. The completed
Defining the research questions is a critical step that PRISMA-P checklist is included as an additional file (see
provides the framework for defining eligibility criteria Additional file 1).
and facilitating good clinical research [14, 15]. This study
will address the following answerable research questions Types of studies
developed based on the PICO (population, intervention, The studies that are of interest for this current investiga-
control, and outcomes) format [18]. Table 1 shows the tion are those that focus on physical therapy intervention
key research questions in PICO format. Accordingly, the in patients with MM who had been actively receiving
specific objectives of the present study is to develop cancer treatment and in follow-up care. However, a pre-
evidence-based guidelines for the following: (1) safe liminary literature search suggested that few randomized
mobilization of patients with MM in an acute care set- controlled trials addressing this topic were available.
ting, (2) effective pain management in patients with Therefore, the guideline development team has decided to
MM, (3) physiotherapy (PT) management in patients include systematic reviews, meta-analyses, interventional
with MM receiving chemotherapy, (4) PT management and observational studies, and case series, which collect-
in patients with MM receiving radiation, (5) PT manage- ively might be informative and helpful in developing the
ment in patients with MM receiving a stem cell trans- guidelines. In addition, a gray literature search will be con-
plantation, and (6) management of fatigue and muscle ducted to ensure that any potential informative articles
weakness in patients with MM. are not missed. Only articles published in the English lan-
guage from the earliest to Aug 2017 will be included.
Study registration and design
This study is registered in the International Prospective Types of participants
Register of Ongoing Systematic Reviews (PROSPERO) Articles with human participants diagnosed with MM of
published by Centre for Reviews and Dissemination, any age, regardless of gender, tumor stage, and type of
University of York, in order to reduce duplication of cancer treatment will be included.
Table 1 PICO (population, intervention, control, and outcomes) Types of interventions/exposure and comparison
Review question What are the available evidence for the following:
Articles examining the effects of exposure or the effects
- Safely mobilizing patients with multiple myeloma of physical therapy interventions including physical activity,
in an acute care setting exercise, and other modalities will be included. Articles
- Effective pain management in patients with
multiple myeloma
with comparison groups with standard interventions or no
- Physiotherapy (PT) management in patients with intervention will be included.
multiple myeloma receiving chemotherapy
- PT management in patients with multiple
Types of outcome measures
myeloma receiving radiation
- PT management in patients with multiple Articles reporting on the following primary outcomes of
myeloma receiving a stem cell transplantation interest will be included: (1) pain, (2) safety, (3) labora-
- Management of fatigue and muscle weakness in
patients with multiple myeloma
tory values, (4) length of stay, (5) range of motion, (6)
muscle strength, (7) balance, (8) gait, (9) endurance, (10)
Population Multiple myeloma or myeloma or plasma cell
myeloma fatigue, (11) physical performance, (12) functional per-
formance, and (13) aerobic capacity. The secondary out-
Intervention Physiotherapy or physical therapy, ambulation,
mobilization, mobility, functional mobility training, comes of interest are (1) quality of life and (2) anxiety/
exercise, strength training, endurance training, depression.
cardio-pulmonary exercise, aerobics exercise,
anaerobic exercise, high-intensity exercise,
low-intensity exercise, home-based exercise, Search strategy
multi-modal exercise, flexibility exercise, physical A detailed literature search will be conducted on the US
activity, pain management, and fatigue National Library of Medicine Database (PubMed), Medical
management
Literature Analysis and Retrieval System Online
Comparator Stated interventions compared with placebo or
no interventions
(MEDLINE), Excerpta Medica Database (EMBASE),
Cumulative Index to Nursing and Allied Health Lite-
Outcomes All possible outcomes
rature (CINAHL), EBSCO, Web of science, Database
Jeevanantham et al. Systematic Reviews (2018) 7:118 Page 4 of 8
of Abstracts of Reviews of Effects (DARE), Cochrane Boolean operators that will be used for each database
Database of Systematic Review, and Physiotherapy Evi- and for each research question, number of articles re-
dence Database (PEDro). All relevant literature from trieved from each database, number of duplicates, and
the abovementioned databases will be retrieved for number of articles that will be archived at each phase
each research question. Table 2 shows the search of review.
terms including the Boolean operators that will be
used for each research question in the PubMed data- Screening and selection of studies
base. A literature search will be conducted by a single Steps recommended by Pai et al. [23] will be followed in
reviewer using relevant subject headings, and key- screening and selecting the studies. Each article in the
words and modifications will be done based on the da- EndNote software will be screened by two independent
tabases searched. All the articles will be retrieved and reviewers. In particular, the titles and abstracts of each
exported to EndNote software. As a first step, a single article will be screened and include articles that meet
reviewer will de-duplicate in EndNote. The research the above described inclusion criteria and exclude all ar-
assistant of the study will maintain a search log re- ticles that are deemed irrelevant. The reviewers will
cording, search strategies, and search terms including meet and resolve any disagreements. Articles will be
included if both the reviewers are in agreement. In case of Guidelines for Research and Evaluation II (AGREE
of disagreement, a third reviewer will be involved in the II) tool [29] to ascertain adequate quality and appropri-
decision-making. All articles identified in the phase I ateness of the evidence to be used in guideline develop-
screening process by mutual consent will be included in ment. The above-described tools are recommended by
the phase II screening. In the phase II screening, full the APTA [16] and have been used in guideline devel-
texts of all the identified articles in phase I screening will opment by other groups [17, 30, 31]. Critical appraisals
be thoroughly read and screened for the inclusion cri- will be performed by two independent reviewers. The
teria by two independent reviewers. Articles considered two reviewers will undergo training and will practice
eligible after full-text view by mutual consent will be in- the critical appraisal tools before doing the actual criti-
cluded in the final analysis. The research assistant will cal appraisals. The scores between the two reviewers
continue to keep track of the number of articles and the will be compared, and discrepancies will be resolved. A
rationale of excluding the articles at each of the screening third reviewer will be involved upon disagreement.
phases. The research assistant will develop a flow diagram Scientific conclusions will be drawn and recommenda-
to report the number of articles included and excluded tions will be made based on the critical appraisals, the
and the selection process as per the PRISMA guidelines. guideline development team’s (team with expertise on on-
cology, physiotherapy, exercise specialists, clinical psych-
Data extraction and management ology, teaching, and research) judgment about the overall
Two independent reviewers will extract the data from all quality of the studies and consensus from the expert group.
the articles that are included in the final selection phase
using a standardized data extraction form. The standard- Levels of evidence
ized data extraction form will be customized from the data The levels of evidence for each article will be determined
extraction and assessment template proposed by “The based on the recommendations of Kaplan and colleagues
Cochrane Public Health Group” [24]. Data extracted by [32] and critical appraisal scores. Evidence obtained from
mutual consent will be included for the final review. A high-quality studies (≥ 50% critical appraisal scores) will
third reviewer will assist in the decision-making upon dis- be assigned “level I” and evidence obtained from lesser
agreement between the two primary reviewers. The data quality studies (< 50% critical appraisal scores) will be
extraction form will be pilot tested with two articles and assigned “level II.” Studies with unacceptable quality will
will be revised based on suggestions by the team mem- be excluded from consideration in the guideline. Table 3
bers. The following data will be extracted from each shows the description of the levels of evidence that will be
article: (1) general study details: Title, authors, source, used for determining levels of evidence of the articles.
country of study, publication type, and year of publica-
tion; (2) study eligibility: type of study, participants Grades of action statements
characteristics including, number of participants, age, The Grading of Recommendations, Assessment, Develop-
gender, diagnosis, type of cancer treatment, stage of ment and Evaluation (GRADE) will be used to determine
cancer, inclusion/exclusion criteria, setting, methods the strength of evidence [33]. See Table 4 for the criteria for
including design/allocation, blinding, sampling, loss to the grades of recommendations for action statements. The
follow-up, recruitment rates, retention rates, and ad- guideline development team will use their judgment and
herence rates, intervention characteristics including
type of exercise/physical activity, types of outcome Table 3 Levels of evidence
measures including self-reported outcomes, objective Level Criteria
outcomes; (3) study details: aim of study, aim of inter- I Evidence obtained from high-quality diagnostic studies,
prognostic or prospective studies, cohort studies or
vention, details of intervention including, setting, strat- randomized controlled trials, meta analyses or systematic
egies used, frequency, intensity, duration, program reviews (critical appraisal score > 50% of criteria).
length, provider, co-interventions, subgroups, details of II Evidence obtained from lesser-quality diagnostic studies,
outcomes, and results of the study. The data extraction prognostic or prospective studies, cohort studies or
will be documented in a Microsoft Excel spreadsheet. randomized controlled trials, meta
analyses or systematic reviews (eg, weaker diagnostic criteria
and reference standards, improper randomization, no blinding,
Critical appraisal process <80% follow-up) (critical appraisal score <50% of criteria).
Each article will be critically appraised using standard- III Case-controlled studies or retrospective studies
ized critical appraisal tools including the PEDro scale, IV Case studies and case series
the Methodological Index for Non-Randomized Studies
V Expert opinion
(MINORS), the Critical Appraisal Skills Programme
Reprinted from Kaplan SL, Coulter C, Fetters L. Developing evidence-based
(CASP) checklists [25], the Measurement Tool to Assess physical therapy clinical practice guidelines. Pediatr Phys Ther. 2013;25:257–
Systematic Reviews (AMSTAR) [26–28], and the Appraisal 270, with permission of Wolters Kluwer Health Inc.
Jeevanantham et al. Systematic Reviews (2018) 7:118 Page 6 of 8
Table 4 Definition of Grades of Recommendation for action as recommended by the APTA. The action statements
statements will be described in terms of Who, When (under what
Grade Recommendation Quality of Evidence specific conditions), Must, Should, or May (the level of
A Strong A preponderance of level I studies, obligation), Do what (precise action), and to Whom. Ac-
but least 1 level I study directly on the tion statements will be supplemented by action state-
topic support the recommendation.
ment profiles listing aggregate decisions made by the
B Moderate A preponderance of level II studies guideline development team and consensus process. The
but at least 1 level II study directly on
topic support the recommendation. action statement profiles will include the following head-
ings: aggregate evidence quality, level of confidence in
C Weak A single level II study at less than
25% critical appraisal score or a evidence, benefits, risks, harm, costs, benefit-harm as-
preponderance of level III and IV sessment, value judgments, intentional vagueness, role
studies, including statements of of patient preferences, exceptions, policy level, and dif-
consensus by content experts support
the recommendation. ferences of opinion [16, 34].
D Theoretical/foundational A preponderance of evidence from
animal or cadaver studies, from Consensus process
conceptual/theoretical models/ Five physiotherapists across Canada experienced with
principles, or from basic science/
bench research, or published expert
the care of patients with MM will independently review
opinion in peer-reviewed journals the contents of the guidelines and provide feedback. Ag-
supports the recommendation. gregate level of evidence will be assigned after the group
P Best practice Recommended practice based on reaches consensus on the evidence supporting each key
current clinical practice norms, action statement. The guidelines will be revised till 80%
exceptional situations where validating
studies have not or cannot be consensus is achieved on each of the statements and
performed and there is a clear benefit, profiles. Action statements that do not reach 80% con-
harm, or cost, and/or the clinical sensus after three rounds of consensus process will be
experience of the guideline
development group. removed from the guideline document.
R Research There is an absence of research on
the topic, or higher-quality studies Internal review
conducted on the topic disagree with Three independent reviewers will evaluate the guideline
respect to their conclusions. using AGREE II. It is a reliable and valid instrument
The recommendation is based on these
conflicting or absent studies. used to assess the quality of clinical practice guidelines.
Reprinted from Kaplan SL, Coulter C, Fetters L. Developing evidence-based AGREE II consists of 23 items clustered under 6 do-
physical therapy clinical practice guidelines. Pediatr Phys Ther. 2013;25:257– mains (scope and purpose, stakeholder involvement,
270, with permission of Wolters Kluwer Health Inc.
rigor of development, clarity of presentation, applicability,
and editorial independence) developed to assess the qual-
weigh the quality of the collective evidence and potential ity of the guidelines. Each item in the questionnaire is
benefit against potential harm for assigning grades to the evaluated on a 7-point scale where score 1 refers to strong
action statements as recommended by the APTA [16]. disagreement and score 7 refers to strong agreement.
External review
Linking levels of evidence and grades of action
The guideline will undergo two external reviews. The
statements
guideline will be sent to CPA for feedback from physio-
The following terms will be used in describing levels of
therapists. The guideline will also be reviewed by a
obligation as recommended by the APTA ([16], pg. 32).
methodological expert from Evidence-Based Care - Cancer
The term must will be used if the evidence supports a
Care Ontario. The draft guideline will be posted on the
strong recommendation (grade A) and harm might
Health Sciences North (HSN) website for public comment.
occur if the action is not followed. The term should will
be used if the evidence supports a strong (grade A) or
Strengths and limitation of this study
moderate (grade B) recommendation. The terms may or
This study will employ validated methodologies such as
could will be used if the evidence is weak (grade C).
PICO guidelines, systematic reviews, and consensus
process. This study will also use standardized quality as-
Creating action statements sessment tools for specific research designs. The litera-
Recommendations will be made in the form of action ture search and data extraction processes will be done
statements. Brief, precise, quality-driven action-oriented by independent reviewers thereby enhancing the validity
statements will be created using a BRIDGE-Wiz software of the study. Additionally, the review panel will consist
Jeevanantham et al. Systematic Reviews (2018) 7:118 Page 7 of 8
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