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lifecycle approach. The Annex I of the MDR require that manufacturers reduce risks as
far as possible, and to do this, manufacturers must estimate and evaluate the risks
associated with, and occurring during, the intended use and during reasonably
foreseeable misuse.
46
The determination as to which risks require the generation of clinical data to support either
the probability and severity of a particular harm, or the effectiveness of a risk control
measure, is one which must be reached upon a case by case basis,
47
and the decision
as to when it is necessary to generate further clinical data is not addressed by ISO 14971
and should be an output of the process of clinical evaluation.
Considerations on aspects of risk evaluation, and considerations on the number of
patients needed to obtain sufficient data can be found in Appendix A7 of MEDDEV 2.7/1
rev. 4.
c. Benefit-risk determination, state of the art, alternative treatment options
The MDR requires that any risks which may be associated with the use of the device are
“compatible with a high level of protection of health and safety, taking into account the
generally acknowledged state of the art”
48
and that the determination of the acceptability
of the benefit-risk ratio is “based on the state of the art in medicine”.
49
It is important to remember that a medical device may be used for an indication for which
there are many alternative medical options. This may include the use of medicinal
products, other medical devices, other medical or allied health professional interventions,
a combination of any of these or no intervention. As such, in order to determine a benefit-
risk ratio, up-to-date alternatives must be considered for legacy devices. The
appropriateness and relevance of an alternative treatment option depends upon a wide
range of factors, including the nature of the healthcare system and patient preferences.
To help to describe alternatives, it is necessary to describe the ‘state of the art’ for the
treatment of the indicated clinical condition taking alternative treatments into account. The
state of the art in this context can be taken to mean the generally accepted most effective
treatment option, for the intended purpose relevant to the device under consideration.
Occasionally, this may be subject to differences of opinion between clinical evaluators as
to what is the state of the art, and where such differences exist, these should be described
and taken into account insofar as is possible. In such cases, a thorough evaluation of the
results from published clinical studies of high methodological quality shall be taken into
account. Moreover, where applicable, particular attention shall be paid to therapy
guidelines grounded on principles of evidence based medicine. Novel and innovative
device technology may be subject to a rapidly evolving state of the art for a particular
indication, and where this exists, it should also be noted.
Aspects that influence the acceptability of benefits and risks can be found in Appendix
A7.2 letter (e) and in Appendix A7.4 of MEDDEV 2.7/1 rev. 4.
46
MDR, Annex I, Chapter 1, section 3(c).
47
ISO14971:2007, page v, notes that an individual’s perception of risk can depend upon a range of factors including their cultural
background, the socio-economic and educational background of the society concerned, the actual and perceived state of health of
the patient, and many other factors.
48
MDR, Annex I, Chapter 1, Section 1.
49
MDR, Annex XIV, Part A, Section 1(a).