This systematic review will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [
12]. Because this review will only use publically available information, an ethics review board approval will not be required.
Search strategy and search term development
A review of the literature will be conducted to identify published studies from the following bibliographic databases: Ovid MEDLINE, Ovid EMBASE, Cochrane Library, EconLit, BIOSIS, WHOLIS, PAIS International, and Scopus. Due to social science work within the area, a manual review of relevant journals will also be carried out.
The search strategy will be developed using keywords and controlled vocabulary terms (e.g., National Library of Medicine’s Medical Subject Headings). Additional papers will be obtained through the use of citation-tracking software, pursuing bibliographical references of papers electronically identified in the database searches and through further exploration of gray literature (Tables
2 and
3).
Table 2
Database search summary
MEDLINE (OvidSP) | 145 | 62 |
EMBASE (OvidSP) | 1580 | 194 |
Cochrane Library & HEED | 104 | 0 |
EconLit (ProQuest) | 296 | 29 |
BIOSIS & Web of Science (Thomson Reuters) | 159 | 37 |
WHOLIS, WHO Library Database | 12 | 0 |
PAIS International, ProQuest | 12 | 8 |
Scopus | 1181 | 147 |
Gray literature/hand search | – | 31 |
Subtotal (n =) | 3489 (3520 inc gray) | 508 |
Duplicates | | 146 |
Total | | 362 |
Subject heading | Clinical adoption MeSH: Technology assessment, Biomedical, Cost-Benefit Analysis
| Cell-based therapeutics MeSH: Cell- and Tissue-Based Therapy, MeSH: biological therapy, MeSH: Regenerative Medicine | Conventional therapeutics MeSH: Therapeutics, Drug Therapy, Enzyme therapy, Molecular Targeted Therapy, Immunotherapy, Transplantation, Monoclonal Antibodies, Vaccines, biosimilars, small-molecule drugs | Emerging technologies MeSH: technology assessment, Biomedical, High-Cost Technology | Barriers |
Keywords | Clinical adoption, implementation, technology assessment, appraisal, tools, methodology, commercialization | Biologics, gene therapy, regenerative medicines, cell- and tissue-based therapy, stem cells, tissue engineering | Medicines, pharmacological agents, organ transplant, monoclonal, vaccine | Translational medical research | |
Key data regarding electronic database and Thomson Reuters Cortellis™ searches is provided below.
The above electronic databases were first accessed on 17 November 2015.
Key words and medical subheadings:
Subheadings: cell therapy; biomedical technology assessment; cost benefit analysis; financial management; economic aspect; commercial phenomena; biological therapy; cell therapy; cost; healthcare cost; stem cell; regenerative medicine
Key words: commercialization; cell therapy; reimbursement; barrier; regenerative medicine
Thomson Reuters Cortellis™ Competitive Intelligence Software:
This software will be searched to identify cell therapy products from 01/01/2010 to 01/05/2016 (access date: 01/05/2016). Identified products will be stratified by phase, i.e., launched (in market) or in discovery phase.
Key search terms: cell therapy; gene therapy (limited to AAV and lentivirus); mesenchymal stem cell
Synthesis
The data synthesis and extraction scorecard will be categorized into eight key domains, which are outlined below:
2.
Regulation and intellectual property
Such domains were identified as being key through brief review of the literature in the area. Each domain will be further subcategorized into important components, e.g., within the
Manufacturing domain, subcategories will include
Scalability,
Automation, and
Supply Chain. The tabulated scorecard serves to:
i.
Facilitate the assignment of a perceived impact and/or importance score
ii.
Serve as a record of frequency for which a barrier/domain was mentioned in a manuscript
The data synthesis and extraction scorecard will be piloted on a sample of 23 manuscripts and completed by two independent reviewers. The pilot sample will be acquired from the 83 records identified by stratifying them according to highest impact factor journal (n = 13) and number of paper citations (n = 10). The scorecard will subsequently be applied to all 83 identified records and completed by two independent reviewers. The IRR (inter-rater reliability) will be calculated following analysis.
The data synthesis and extraction scorecard will score each paper on the perceived impact and importance of a cited factor, as seen below in Table
4.
Table 4
Data synthesis and extraction scorecard excerpt
Essential (4) | Major (3) | Moderate (2) | Negligible (1) |
Imperative barrier, definitive consideration | High priority, key consideration | Lower value or narrower impact | Low priority or relevance to field, minimal impact |
The excerpt above displays a linear scale ranging from Essential to Negligible, which is accompanied by a numerical value (see parenthesis). The scorecard will also facilitate the documentation of additional information, including publication details (e.g., year, journal, country of publication), cell-based therapy characteristics (e.g., therapeutic indication, autologous vs. allogeneic, cell type), generalizability (e.g., if nature of findings are limited to a particular region by the regulatory system described), and sources of funding and potential conflicts of interest. An additional free text box will be included for “other” challenges or barriers identified in the reviewed manuscripts that did not fall into one of the predetermined domains or subcategories.
A PRISMA-P file is included as Additional file
1. There is no PROSPERO registration number.