Review question

The purpose for conducting this scoping review is to map the evidence as it relates to time from diagnosis to treatment among adults living with MM. Our sub questions include:

1. Identify definitions and measures of TTI in MM.
2. Characterize reported time frames from diagnosis to treatment initiation.
3. Explore factors associated with delays in treatment.
4. Assess the impact of TTI on clinical outcomes (OS, PFS, symptom burden).
5. Identify gaps for future research.

Types of sources

This scoping review will consider experimental and quasi-experimental study designs (e.g., randomized controlled trials, non-randomized controlled trials, interrupted time-series studies). Observational studies including prospective and retrospective cohort studies, case-control studies and cross-sectional studies, and descriptive observational study designs will be considered for inclusion. Systematic reviews, commentaries and opinion papers will also be considered for inclusion in this scoping review.

Search strategy

An initial limited search in PubMed was undertaken to identify articles on the time to treatment in MM. Terms used in the titles and abstracts of relevant articles, and the index terms used to describe the articles were used to develop a full search strategy for PubMed under the guidance of a Health Sciences librarian (JC) (see Appendix II in S1 File).

Our search strategy was guided by the concepts identified in Table 1. Studies published in any language will be included where English translations are available. If English translations are not available these sources will be excluded. Studies published in or after the year 2000 will be included. Treatments for MM before 2000 were only moderately effective, and highly toxic dampening enthusiasm for early treatment. Since then, the treatment landscape has shifted dramatically, with more than 30 FDA approvals [10]. The increasing effectiveness and tolerability of new treatments have changed the costs and benefits of earlier treatment dramatically. Now there is a strong rationale and an increased appetite for earlier treatment which led to our decision to limit the search in this way.

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Table 1. Frame for review question and important literature search concepts.

https://doi.org/10.1371/journal.pone.0330907.t001

To validate our search strategy, we a priori identified four sources that a search strategy must identify to successfully achieve our aim of uncovering sources related to time to treatment among adults with newly diagnosed multiple myeloma, and then made sure our search strategy did in fact identify these sources. After validation of our search strategy, including all identified keywords and index terms, it was adapted for CINAHL Plus with Full Text (EBSCOhost), Scopus and Embase (Elsevier).

Study/source of evidence selection

Following the search, identified citations will be uploaded into EndNote X9 (Clarivate Analytics, PA, USA) and duplicates removed. De-Duplicated citations will be uploaded into Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia).

Screening will occur following a screening pilot test in which we will screen 25 sources and refine and modify our initial inclusion/exclusion criteria based on our search strategy concepts (Table 1). Reviewers will not be blinded during the screening process. Titles and abstracts will then be screened by two independent reviewers for inclusion in the review. Full text of sources identified for further review will be assessed independently by two reviewers for final inclusion. Reasons for exclusion of sources during full text review will be recorded and reported. After full text sources have been selected for inclusion, we will screen sources in their reference lists and also screen sources that have cited these included sources (identified in SCOPUS) using the procedures outlined above. Any disagreements that arise between reviewers at each stage of the selection process will be resolved through discussion until consensus.

The results of the search and the study inclusion process will be reported in full in the final scoping review and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR) flow diagram [11].

Data extraction

Data will be extracted from papers included in the scoping review by two or more independent reviewers using a data extraction tool developed by the reviewers. The data extracted will include specific details about the participants, concept, context, study methods and key findings relevant to the review question/s.

A draft extraction form is provided (see Appendix III in S1 File). The draft data extraction tool will be modified and revised as necessary during the process of extracting data from each included evidence source. Modifications will be detailed in the scoping review. Any disagreements that arise between the reviewers will be resolved through discussion. If appropriate, authors of papers will be contacted to request missing or additional data, where required.

Data analysis and presentation

Data will be summarized narratively and organized around answering our scoping review questions. We will summarize the ways time to treatment is defined and measured in the literature. We will describe narratively how sources defined and/or conceptualized time to treatment. We will characterize reported time frames of time to treatment in myeloma. Results will be stratified by transplant eligibility and induction treatment regimen as the data allows. We will describe factors associated with delays in treatment identified. We will summarize the ways the impact of time to treatment on clinical outcomes (survival, symptom burden) has been explored, and we will identify gaps in our knowledge on time to treatment in myeloma to guide future research.