Literature Search Protocol (LSP)

Within the Clinical Evaluation Plan (CEP), a clear and systematic articulation of the literature search plan (LSP) and methodology is of critical importance. This section, whether outlined in the main body of the CEP and detailed in an appendix or presented as a standalone chapter, has the core purpose of prospectively defining a scientific, rigorous, and reproducible process for comprehensively and objectively identifying and retrieving published scientific literature and safety data relevant to the device under evaluation. A well-thought-out Literature Search Protocol is a key safeguard for ensuring that the external evidence upon which the clinical evaluation relies is both sufficient and unbiased.

The LSP should clearly delineate the complete strategy, from defining search objectives to the final selection of literature.

Defining the Objectives and Scope of the Literature Search

The core objectives that the literature search aims to achieve must be clearly defined. These objectives typically align closely with the overall goals of the clinical evaluation and may include (but are not limited to):

• Establishing the current State-of-the-Art (SOTA) for the relevant medical field, device type, and specific clinical conditions.
• Gathering clinical data and safety/performance information on the device under evaluation itself (if any publicly available studies or reports exist).
• Identifying and obtaining clinical data on similar devices, benchmark devices, or identified equivalent devices for comparative analysis or to support claims of equivalence.
• Collecting information on potential clinical hazards, adverse events, complications , and known risks associated with this class of device or technology.

After clarifying the objectives, the scope of the literature search should be defined. This includes determining the time period for the search (e.g., the last 5 years, 10 years, or a specific window based on the pace of technological development and product characteristics), language preferences for literature (typically English-dominant), and any particular device characteristics, clinical application scenarios, or patient subgroups that will be prioritized during the search.

Formulating Clear Research Questions

To make the literature search more targeted and effective, prospectively defining clear research questions is an indispensable step. These questions should stem from the core objectives of the clinical evaluation, the intended use of the device under evaluation, its key clinical claims, and any uncertainties or information gaps identified during risk assessment or review of existing data.

Research questions can be organized around different themes, such as:

• Research questions for the State-of-the-Art (SOTA): These questions aim to comprehensively understand the current treatment landscape for the relevant disease, mainstream technologies, alternative therapies, and their respective clinical safety and performance profiles.
• Research questions for device-specific searches (including the device under evaluation, similar/equivalent/benchmark devices): These questions are more focused on gathering directly relevant clinical evidence to assess the specific safety and performance of these devices or to conduct head-to-head comparisons.

Developing a Comprehensive Search Strategy

The search strategy is the heart of the Literature Search Protocol, detailing how the required information will be systematically sought.

Selection of Data Sources: The types of databases and information sources to be searched must be clearly specified.

Development of Search Terms and Search Strings: This is a critical technical aspect for ensuring the comprehensiveness and accuracy of the search. A systematic approach to selecting and combining search terms should be described.

• Foundational Information Gathering: Conducting broad preliminary information gathering before constructing complex database search strings is highly beneficial. This helps to comprehensively understand the relevant disease context, current clinical practices, authoritative guideline recommendations, key safety and performance evaluation metrics, and unmet medical needs. This initial exploration (which can utilize general search engines like Google Scholar) lays the foundation for the subsequent selection and optimization of precise search terms.
• Selection and Combination of Core Search Terms: A systematic list of keywords should be developed around the characteristics of the device under evaluation (e.g., generic name, technological principle, key components), its intended use (relevant diseases, indications, surgical procedures), target population, clinical outcomes of interest (e.g., safety indicators, performance indicators, efficacy indicators), and comparator devices (e.g., trade names, generic names of similar/equivalent devices).
• Application of Search Logic: Explain how Boolean operators (AND, OR, NOT), truncation symbols, wildcards, and field tags (e.g., title, abstract, keyword fields) will be used to combine these keywords into specific search strings adapted for the syntax of different databases.
• Tailoring Strategies for Different Search Objectives: The emphasis and combination of search terms may differ when searching for SOTA, the device under evaluation, or similar/equivalent/benchmark devices. These should be considered and planned separately.

Application of Search Limits and Filters: Specify if and how any particular search limits will be applied, such as publication date ranges, language of literature, or study types (e.g., RCTs, systematic reviews). However, caution is advised when using study type filters for safety-related searches, as important signals from non-traditional studies (like case reports, adverse event databases) might be missed.

Planning the Literature Screening and Selection Process

After executing the searches and obtaining initial results, the CEP must plan a systematic and transparent literature screening process to accurately identify truly relevant publications.

• Inclusion and Exclusion Criteria: Emphasize the necessity of pre-defining clear and specific criteria for including or excluding literature at each stage of screening (e.g., title and abstract review, full-text review). These criteria should be directly derived from the previously established research questions and evaluation scope.
• Execution of the Screening Process: Briefly describe how the screening process is planned to be carried out.

Data Extraction and Documentation of the Search Process

The CEP should also briefly mention the plan for systematically extracting relevant data from the finally included literature (e.g., a pre-designed data extraction form specifying key information fields can be developed).

The entire literature search process—from database selection, search dates, full search strings actually used, number of hits from each database, to the number of articles included/excluded at each screening stage (presented in the CER using a PRISMA flow diagram or similar)—will be fully and meticulously documented. Such comprehensive documentation is fundamental to ensuring the transparency, reproducibility, and auditability of the literature search process.

Linkage to Data Appraisal

All literature identified as pertinent through this systematic search process will proceed to the next step—rigorous data appraisal according to the methodology planned in the “Appraisal and Analysis of Pertinent Data” chapter of the CEP.

By planning and articulating the Literature Search Protocol in this manner, it ensures that the literature evidence relied upon for the clinical evaluation is obtained through a systematic, comprehensive, unbiased, and reproducible process, thereby providing high-quality input for subsequent data appraisal, analysis, and ultimately, the conclusions of the clinical evaluation.