FROM SETTING THE GOAL TO THE LITERATURE SEARCH AND REVIEW PROTOCOL
In the forthcoming three part blog series, we would like to shed more light on the Literature Review process in accordance with the Medical Device Regulation (MDR).
In today’s blog, we will focus on the initial steps necessary for the planning of the literature search and review protocol.
Before we start, let’s keep in mind that:
- Technical documentation and clinical evaluation form the basis of the assessment for medical device conformity.
- A clinical evaluation is mandatory for medical devices of all risk classes.
- Clinical evaluation is a process where all significant clinical data concerning a medical device is gathered and subsequently evaluated.
- The Clinical Evaluation Report (CER) serves as an ID for the product and it analyses whether there is sufficient evidence to demonstrate product safety and efficacy.
A cornerstone for a compliant CER is a systematic and methodical literature review. It is crucial to plan every stage of this process in order to identify all the relevant published literature for the device and the claims made about it. A literature review consists of two phases – the literature search and the evaluation of the available literature.
In the following paragraphs, we will show:
- How to undertake a successful literature search
- How to write a literature search and review protocol
Before entering the clinical evaluation process, always use the valuable information provided in the guidelines, read them carefully:
CLINICAL EVALUATION: A GUIDE FOR MANUFACTURERS AND NOTIFIED BODIES UNDER DIRECTIVES 93/42/EEC and 90/385/EEC. MEDDEV 27/1 revision 4. 2016., A5, Literature search and literature review protocol, key elements”
MDCG document 2020-13, Clinical evaluation assessment report template, Section D
The Three steps to a successful literature search
Step One: Determine what should be found
It is very important to understand that the literature search needs to cover two categories of data:
- Clinical data on the medical device in question or its equivalent device and
- Data for the state of the art which may relate directly to the device in question and/or to equivalent devices, benchmark devices and similar devices and technologies as well as to the medical alternatives available to the intended patient population.
If a manufacturer possesses its own clinical data for the device, this is a definite plus. The literature is then considered together with the data to enable a consistent appraisal and overall analysis.
According to Section D of MDCG 2020-13:
“The clinical evaluation should clearly describe the selection criteria with respect to the regulatory purpose to which it will apply. The CER should clearly differentiate between the two types of data (device under evaluation or an equivalent device, state of the art or alternative treatment option). If the data does not relate to either of the above, provide a rationale with respect to its inclusion.”
Step Two: Understand the goal
The goal is to identify published scientific papers (reviews, clinical trials, meta-analyses) that hold valid results regarding the safety, performance and clinical benefits of the medical device in question and the state of the art for the device. The literature search should be precise, detailed and systematically documented.
The selection of literature should be objective and justified which means it should include all the relevant data, both favorable and unfavorable.
The selected papers should reflect the intended use of the device and this should be kept in mind when considering writing a literature methodology i.e., a literature search and review protocol.
Step Three: Write a Literature Search and Review Protocol
A Literature Search and Review Protocol should contain:
- Research question
- Databases that will be used
- Terms that will be used
- Inclusion/exclusion criteria
- Search methods used in the literature evaluation
- How the duplication of data from multiple sources will be addressed
- How data integrity will be ensured (e.g., quality control/second review of extracted data by additional reviewer)
- How each data source will be appraised and its relevance to the device in question
- How the data will be analyzed and processed
For more specifics on this, please see Appendix A5 in MEDDEV 2.7/1 Rev. 4.
The research question should be consistent with the scope of the clinical evaluation and carefully constructed using a PICO method or its variations.
PICO is a framework for creating a good clinical research question. It is a mnemonic used to describe the four elements of a clinical question:
- P = Population/Patient/Problem– How would I describe the problem or a group of patients similar to mine?
- I = Intervention– What main intervention, prognostic factor or exposure am I considering?
- C = Comparison– Is there an alternative to compare the intervention with? (optional)
- O = Outcome– What do I hope to accomplish, measure, improve or affect?
Let’s offer an example:
Research question: What are the risks of the use of splints as a limb immobilization method in patients with limb fractures or sprains?
P = Population/Patient/Problem: patients with limb fractures or sprains
I = Intervention: splints as a limb immobilization method
C = Comparison: none
O = Outcome: identify risks
If PICO is not sufficient to describe the key elements of all the questions in the desired medical field, sometimes the use of either the SPIDER (sample, phenomenon of Interest, design, evaluation, research type) or SPICE (setting, perspective, intervention, comparison, evaluation) methods is preferable.
Depending on the research question and the type of evidence needed, a number of databases could be selected.
MEDDEV 2.7/1 Revision 4’s Annex 4 recommends these databases:
- PubMed/Medicine: a solid baseline for starting the research
- EMBASE: provides complete information regarding the coverage of medical devices and therapies used in Europe
- Cochrane CENTRAL trials register: provides complete information regarding trials in Europe
MEDLINE (PubMed) and EMBASE are the leading literature databases while Cochrane is the leading option for controlled trials.
Cochrane Central Register of Controlled Trials (CENTRAL): www.cochranelibrary.com
Search terms can be both keywords and subject or index terms (MeSH terms) with both being useful and therefore advisable to use in the search. Keywords will help to broaden the results while index/subject terms will help to focus the search by seeking items that have had a specific term applied by an indexer.
However, the best approach is to combine these by using Boolean logic. There are three main Boolean operators – AND, OR and NOT and using these allows you to combine search terms in specific ways to broaden or narrow your results. Quotation marks and round brackets are also useful tools for improving the quality of the search process.
We want to undertake a search to find articles on state of the art for traction splints for femoral fractures.
Having found these MeSH terms – traction, splints, immobilization, femoral fractures – we can now combine these with the Boolean operators:
Traction AND (Splints OR Immobilization) AND Femoral Fractures
We will discuss these search combinations further in Part Two of this blog series.
These are the boundaries that must be set before the search is conducted; however scoping searches may need to be undertaken to determine the appropriate criteria.
Common Inclusion/Exclusion criteria are:
- Study design
- Type of publication
- Geographic location
- Peer review
For example, for our search for traction splints, we could set the following boundaries:
Review, Systematic Review, Humans, English. 2000-2020.
Always bear in mind that the Literature Search Protocol must be well constructed and precise since it forms the basis of every other step in the clinical evaluation process.
For notified bodies, just one look at your Protocol should demonstrate that you are serious, competent and that their own job of evaluation will be much easier with the aid of a clear and professionally written Literature Search Protocol.
In the next blog, we will focus on how to conduct a database search and analyse the search results.
Literature Search and Review at BioReg Services
BioReg Services specializes in systematic literature searches and reviews in compliance with the MDR Regulation (EU) 2017/745. Our team can design a comprehensive literature search protocol with complete documentation of the literature screening and data extraction process. We can obtain clinical evidence for the literature review for your new medical device or we can update the literature review of a CE-marked or legacy device to create an MDR compliant document.
Our unique skill set that makes us super qualified is that we are experienced in natural sciences, regulatory processes and scientific literature research. We think together so we can approach problem solving from different points of view. Clients can rely on us; we add the benefits of trust, knowledge and persistence on the journey to a MDR compliant destination.