Literature review for In Vitro Diagnostic (IVD) devices

Literature Review for In Vitro Diagnostic (IVD) devices

A systematic review literature search is a method to collect the clinical data for the performance evaluation of in vitro diagnostics (IVDs). A systematic assessment and analysis of clinical data requires to establish and verify the device's scientific validity, as well as its analytical and clinical performance.

A literature review is also required to establish the State of the Art (SOTA) for in vitro diagnostics (IVD) devices. It provides a thorough examination of existing knowledge, technological innovations, and clinical practices. This review plays a crucial role in identifying current standards, benchmarking new diagnostic devices, and ensuring adherence to regulatory requirements. Additionally, it guides future research by analyzing historical trends, findings and highlighting areas that need further exploration, and supporting risk management for identifying new risks with devices working on the same technique or alternative therapies. Furthermore, the review validates claims regarding clinical usability and effectiveness, which are essential for achieving market approval and ensuring patient safety. 

In this blog, we will explore the steps for conducting systematic literature review under the IVDR and how it fits into the performance evaluation process.

The procedures for performing a literature review:

1. Formulate the Research Questions :

Formulation of well-defined research question is important to define specific objective of the literature search. It allows us to identify the relevant clinical data for the performance of an IVD device.

A clearly defined question offers several benefits such as:

• Narrow down the scope of the search, making it easier to identify relevant articles
• It allows to select precise keywords
• To establish Inclusion/Exclusion Criteria
• Identifying Key Outcomes (e.g., accuracy, sensitivity, or clinical utility)
• Streamlining the Review Process
• Synthesizing the findings across articles, making it easier to draw meaningful conclusions

Example of a Well-Defined Research Question:

If your objective is to evaluate the effectiveness of a specific IVD device for diagnosing a disease, your question could be:

"What is the diagnostic accuracy of [specific IVD device] compared to traditional methods for detecting [specific disease] in adult patients?"

2. Literature Search Strategy

The initial step in conducting a literature search is to develop a search strategy that details how to identify relevant literature. This strategy should identify the sources to be searched, along with the search terms to be utilized. Documenting this search strategy as part of the systematic review protocol is essential. The strategy needs to be precise and comprehensive to allow regeneration of data in future with consistent results or to facilitate updates as necessary. This approach improves the reliability of the review and ensures that various reviewers can adhere to the same process without impacting the results.

3. Select Appropriate Databases: 

Analyze all available databases for literature search and select the most appropriate databases that will provide relevant and quality data and a provide a proper justification for selecting databases. Commonly used databases for literature searches include:

• PubMed
• Embase
• Cochrane
• Google Scholar

4. Apply Search Filters: 

Search filters are typically used to narrow down the search results, facilitating the retrieval of the most relevant data for the clinical and performance evaluation. Some commonly applied filters include:

• Date limits
• Study type
• Language limits

5. Creation of Search Terms: 

To develop effective search terms, the author must have a thorough understanding of the subject device, as well as any equivalent, similar, or alternative techniques and therapeutics. Utilizing the PICO framework with Boolean Operators (AND, OR, and NOT) can enhance the relevance of search terms:

• P - Patient, Problem, or Population
• I - Intervention (Device)
• C - Comparison, Control, or Comparator (Standard of Care)
• O - Outcome(s) (Performance and Safety Endpoints)

6. Perform Search:

Perform a comprehensive literature search using predefined search terms in chosen relevant databases (e.g., PubMed, Embase, Google Scholar) and export search results.

7. Identification of Duplicate Data:

After completing the literature search, identify and eliminate duplicate results from the search results to ensure each article is only considered once.

8. Literature Selection:

For selection of relevant literature, there should be pre-defined articles inclusion and exclusion criteria. These criteria can be varied per different type of devices. There are some inclusion and exclusion criteria mentioned below as an example.

Inclusion criteria

• Any articles that focus on specific IVD devices (e.g., molecular tests, immunoassays, point-of-care tests).
• Articles pertaining to a specific disease or condition that the IVD device is intended to diagnose (e.g., infectious diseases, cancer biomarkers).
• Studies must include human subjects relevant to the intended use of the IVD device (e.g., adults, children ,specific demographics).

Exclusion criteria 

• Articles not in English.
• Article does not contain patient data.
• Quality of the article is insufficient.
• Non-human studies (e.g., animal studies)
• Articles lacking sufficient data on performance metrics
• Case reports or anecdotal evidence
• Articles that do not provide clear methodology or outcomes

9. Article data Screening: 

The article data screening process for an IVD literature search can indeed be structured into two main phases: “Title and Abstract Screening” and “Full-Text Screening”.

Title and Abstract Screening

• After removal of duplicate, review the titles and abstracts of the remaining articles to assess their relevance to the research question. 
• Apply inclusion and exclusion criteria to filter out articles that do not meet the requirements.

Full-Text Review

• For articles that pass the title and abstract screening, obtain the full text and conduct a detailed review.
• Evaluate each article against your inclusion criteria (device type, target condition, study design, population, performance metrics, etc.).

10. Data Extraction:

In the data extraction process, it is essential to gather critical details from the relevant articles or reports to substantiate the performance of the device. The following key elements should be extracted and later will be used in different sections of the PER:

• Study characteristics (authors, year, journal)
• Study Objective
• Study Design
• IVD device details (type, intended use)
• Population demographics
• Risks/Benefits of IVD device / technologies 
• Performance outcomes (sensitivity, specificity, etc.)
• Conclusions and implications
• Limitations

11. Data Appraisal:

In the data appraisal process, the PRISMA diagram can be utilized for visual representation of literature data. To evaluate the relevance of this literature, the level of evidence can be established using the Oxford Centre for Evidence-Based Medicine's 2011 Levels of Evidence

Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence

* Level may be graded down on the basis of study quality, imprecision, indirectness (study PICO does not match questions PICO), because of inconsistency between studies, or because the absolute effect size is very small; Level may be graded up if there is a large or very large effect size.

** As always, a systematic review is generally better than an individual study.

Literature search report: 

The literature report must comprehensively document the entire literature review process and its outcome to establish the State of the Art (SOTA). This ensures that the benefit/risk ratio aligns with accepted practices and provides evidence for performance evaluation. The finding from the literature search should be included in the reports on scientific validity, analytical performance, and clinical performance, which help to analyze any new risks that may arise with the use of the device.

Our Expertise:

SARACA has helped 25+ In-Vitro Diagnostics Medical Device Manufacturers in developing technical documentation to get the CE Mark under IVDR. We have developed the 75+ PERs along with Clinical Performance Reports, Scientific Validity Reports and Analytical Performance Reports and Post market Surveillance Report including Post Market Performance Follow up(PMPF), Risk Management Report (RMR), Summary of Safety and Performance (SSP) for several diagnostics areas for class A, B, C, and D In-Vitro Diagnostics devices.

Some of the devices and technologies we have experienced include Flow cytometers, Immunoassay kits, Enzyme immunoassay analyzer, ELISA kits, Monoclonal Antibodies, Protein analysis reagents, Western blotting products, Cell culture mediums, Spectrophotometry devices, Mass spectrometers, Microplates, Hematological kits, Blood analyzers, Molecular diagnostic kits with calibrator, reagents & controls, Biomarkers, Fluorometers , Clinical chemistry analyzer, Self testing devices, Urine testing kits, Pregnancy test kits, Companion diagnostics testing & equipment’s, PCR thermocycler, Cell control kits, Genetic testing devices, Image analysis medical device software’s, Mass Spectrometry Software and many others.