Since the entry into force of Regulation 2017/745 and the Guideline MDCG 2020-6, manufacturers have had to verify the availability and assess the quality of clinical evidence, and therefore, clinical data on their medical device to demonstrate its efficacy and safety.
From an analysis of evidence for insufficient quantity and, in particular, quality, it becomes necessary to collect clinical data on the device.
It is well known that the Regulation mandates the conduct of a clinical investigation for Class III medical devices and implantable devices except in cases where:
- the device has been designed with modifications to a device already marketed by the same manufacturer,
- the manufacturer has demonstrated that the modified device is equivalent to the marketed device, in accordance with Annex XIV, point 3, of Regulation 2017/745 and the notified body has approved such demonstration, and
- the clinical evaluation of the marketed device is sufficient to demonstrate compliance of the modified device with the relevant safety and performance requirements.
The same obligation, which we might also call an obviousness, applies to innovative devices, thus new, not yet introduced to the market.
For legacy medical devices, that are CE marked, therefore, already on the market, manufacturers can use methodological and systematic processes to collect evidence and thus clinical data, other than a clinical study, such as a survey or an analysis of operational data contained within devices equipped with software components.
In both cases, it is important to remember that it is always essential to build an adequate level of evidence supported by the targeted analysis of the scientific literature on the device under examination, in order to gather all available performance and safety information.
The survey is structured as a questionnaire submitted to the user of the medical device or to distributors or healthcare operators (doctors, pharmacists, etc.) who respectively use, convey or prescribe the use of the medical device, in order to collect responses to questions aimed at detecting the performance and safety of the device itself.
Take, for example, a survey formulated and distributed for the collection of clinical data on a substance-based medical device, namely a barrier effect gynecological cream that helps to restore the physiological pH of the vagina and allows the restoration of optimal conditions for the proliferation of natural lactobacilli. The medical device is used to alleviate signs and symptoms usually present in these circumstances or as symptomatic adjunct to antifungal treatment and for the prevention of recurrent vaginal infections.
The survey starts by asking the user of the medical device their age and the circumstances that could have led to the development of vaginal disease.
In order to have data available to evaluate the performance of the gynecological cream, the survey asks to select the present symptoms, in particular the most persistent and for how long, assigning an intensity score from absent to very severe, both before and after the use of the medical device.
It is then asked whether the use of the device, as a preventive treatment, has led to a reduction in episodes of vaginal infection.
With the aim of collecting safety data of the device, the survey asks the user if any adverse effects or reactions occurred after using the vaginal cream. If affirmative, it asks to specify which.
The survey concludes with a request to express an overall judgment on the use of the medical device and, therefore, on the possibility of recommending the cream to another person presenting with vaginal disease.
The data collected through the survey have been analyzed and processed according to statistical methodology to obtain objective data on the performance and safety of the device, statistically significant.
Another possibility of collecting clinical evidence on the medical device is given by the presence of software and hardware components, capable of recording and storing the operating parameters of the medical device while it is used to achieve its intended use.
This is the case, for example, with an active medical device intended for dosing therapy with inhaled nitric oxide (NO) in gaseous form.
The device allows healthcare facility doctors and nurses to dose and monitor the flow of NO and O2 and, at the same time, to ensure with continuous monitoring that the concentration of NO2, a highly toxic gas that could form in the inspiratory ventilation line of a patient undergoing treatment with inhaled nitric oxide (iNO), is kept below safety levels.
The device provides patients with a specific and stable dosage, set by the doctor, of the nitric oxide (NO/N2) mixture, while recording, along with other useful parameters, the desired and supplied gas dosages every 30 seconds.
Moreover, the device has a series of alarms to alert of a problem during therapy.
The data are generated in CSV format directly by the medical device and are available for statistical analysis.
Each therapy log file is created when the device is turned on, and the final record corresponds to the moment when the device is turned off. The duration of the therapy is a few days.
Each therapy log file is associated with a specific machine and a specific therapy (both are identified by an ID).
The alarm log files consist of multiple lines, each corresponding to different alarms that occurred at a particular time.
From the extraction and processing of the medical device's data, it was possible to perform a statistical analysis that provided evidence on the performance and safety of the medical device.
In particular, comparisons between the desired dose and the actual dose, the time required to administer a certain dose from the moment it is specified by the doctor, the average duration of therapies, calculated as the difference between the date/time of the last and first recording of a therapy, are performance parameters of the device.
Variables considered for the demonstration of the medical device's safety were "patient flow" (l/min), "dosing flow" (ml/min), and the amount of "NO" and "NO2" (ppm) delivered.
It was indeed interesting to assess how often the “patient flow” exceeded 120 l/min or the “dosing flow” exceeded 5000 ml/min, as recordings that exceed these thresholds cannot be considered reliable.
For this reason, safety alarms are generated, as well as in the case of an abnormal duration of treatment/therapy.
The above cases are just some examples of how, through the definition of a methodological process of collecting clinical data on a medical device, followed by a statistical analysis of the data itself, it is possible to satisfy the requirement of demonstrating the performance and safety of the medical device by having sufficient clinical evidence.