Table A4.

PRISMA List for LCA2 Studies.

Section/Topic	#	Checklist Item	Reported on Page #
TITLE
Title	1	Identify the report as a systematic review, meta-analysis, or both.	Page 1
ABSTRACT
Structured summary	2	Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implication ns of key findings; systematic review registration number.	Page 53, (Appendix A.7)
BACKGROUND
Rationale	3	Describe the rationale for the review in the context of what is already known.	Page 1–2 (Introduction)
Objectives	4	Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).	Page 2 (Materials and Methods); page 4 (Results); Table S1 (Supplemental).
METHODS
Protocol and registration	5	Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.	Informal proposal/protocol assessed and peer-reviewed at the University of Edinburgh.
Eligibility criteria	6	Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.	Table S1 (Supplemental); Appendix A.4.
Information sources	7	Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.	Table S1 (Supplemental); Appendix A.1. page 15.
Search	8	Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.	Appendix A.1. page 15; Appendix A.2, page 21.
Study selection	9	State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).	Appendix A.2, page 21; Appendix A.3, page 31.
Data collection process	10	Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.	Page 4 (Materials and Methods).
Data items	11	List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.	2 NRSI studies were supported by academic funding (Jacobson 2012, Le Meur 2018); 1 NRSI was supported by both academic and industry funding (Bainbridge 2015); 2 NRSI studies were supported by industry funding (Testa 2013, Weleber 2016); 1 RCT was supported by industry funding (Russell 2017).
Risk of bias in individual studies	12	Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.	Page 4 (Materials and Methods); Appendix A.5 and Appendix A.6.
Summary measures	13	State the principal summary measures (e.g., risk ratio, difference in means).	Page 4 (Materials and Methods).
Synthesis of results	14	Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis.	Page 4 (Materials and Methods); Page 8–16.
Risk of bias across studies	15	Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).	Page 4 (Materials and Methods); Appendix A.5 and Appendix A.6.
Additional analyses	16	Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.	n/a
RESULTS
Study selection	17	Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.	Page 5, Figure 1 (Results)
Study characteristics	18	For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.	Table S1 (Supplemental); Appendix A.2.
Risk of bias within studies	19	Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).	Appendix A.5 and Appendix A.6.
Results of individual studies	20	For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.	Table 3, page 13.
Synthesis of results	21	Present results of each meta-analysis done, including confidence intervals and measures of consistency.	Table 3, page 12.
Risk of bias across studies	22	Present results of any assessment of risk of bias across studies (see Item 15).	Table 2, page 11
DISCUSSION
Summary of evidence	24	Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).	Page 15 (Conclusion); Appendix A.7 (Structured summary).
Limitations	25	Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).	Table 2, Page 11; Appendix A.5 and Appendix A.6.
Conclusions	26	Provide a general interpretation of the results in the context of other evidence, and implications for future research.	Page 15 (Conclusion); Table S4a,b.
FUNDING
Funding	27	Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.	None.