Home /  Open Letter to Experts and Manufacturers concerning (EU) 2017/745

Open Letter to Experts and Manufacturers concerning (EU) 2017/745


Neil Atkins, Medaval Ltd.

30 May 2018

Introduction

Last May, new regulations regarding the medical devices were introduced by the European Parliament and the Council of The European Union. [1] These must be adopted by member states by 20 May 2020 and come into force from that date, or six months after adoption, whichever is the later. They will, therefore, be in force in all member states by 20 November 2020.

These regulations have to be welcomed, particularly when considered in the light of the recommendations the editorial published last August by Eoin O’Brien and George Stergiou and those in the EHL policy statement of 2016. [2, 3]

Validations and equivalences that do not comply with these regulations will not be applicable from the date of enforcement.

This has several implications for blood pressure monitors that need to be addressed so that manufacturers can be in compliance, in advance of that date, to ensure that validations and equivalences will apply.

Validations under (EU) 2017/745

A consensus document on a universal protocol has been published. [4, 5] It is now important that the protocol proper is completed, so that all new publications from 20 May 2020 use this protocol so that it ties in both with the new regulations and also the call for this to be the mandatory protocol [2]. For this to happen it should be published ideally by the 20 May 2019, providing notice of at least one year.

In the light of the regulations and also the call to “Improve validation procedures by providing safeguards for performance, analysis, and reporting of validation results” [2], the protocol should include an Appendix with a checklist and forms.

Violations made in validation studies have been well documented [6]. Most of these are due to misunderstandings and omissions made by both investigators and reviewers. A checklist of requirements and forms will make it clear both for investigators and reviewers as to what is required. This exercise has already been completed when the Medaval Accreditation Procedure was drawn up for the current ESH-IP 2010 and AAMI/ANSI/ISO 81060-2:2013 protocols and it has been tested for 30 devices.

This can be adapted for inclusion in the new universal protocol in order to eliminate any excuses for protocol violations and to provide the necessary safeguards. A huge amount of work went into the accreditation procedure. Of particular importance is how it addresses validations in special groups, where it is impossible to prescribe for every eventuality in a standard protocol. Instead, fundamental scientific principles are demanded so that, if the sample requires, by its very nature, a variation, the list requires the investigator to support this with appropriate literature. Ad-hoc validations or amendments have to be eliminated from validations.

Another important inclusion that should be made is a sunset statement for current validations carried out by ESH-IP 2010, AAMI/ANSI/ISO 81060-2:2013 and also by all previous protocols. This is important, not only for Regulations compliance, but it will provide an unequivocal line and a date from which the only validation that will matter will be those carried out according to the universal protocol. To be fair to manufacturers who have already carried out validations, and to ensure that they continue to do so in the interim period, there will have to be a reasonable date, perhaps 20 May 2025, from which validations by any protocol other than the universal protocol will no longer be recognised.

Equivalences under (EU) 2017/745

By far, the biggest implications of the new regulations are for equivalences. No existing equivalence will apply anywhere in the EU from 20 November 2020. Relevant sections from the Regulations are included in the Appendix A below. While the Regulations do not include details of how an equivalence should be performed, the clear similarity of PART A (Clinical Evaluation)of ANNEX XIV (Clinical Evaluation and Post-Market Clinical Follow-Up)to Appendix A1 (Demonstration of equivalence)of MEDDEV 2.7/1 revision 4[7] (see Appendix B below) cannot be ignored. Early last-year, following a lot of work and valuable input and insight by many experts, the Medaval Comparative-Equivalence procedure was completed specifically to ensure compliance with MEDDEV 2.7/1 rev 4. This means that the protocol that will ensure compliance with (EU) 2017/745 has been written already.

These regulations for equivalence are extremely important and detailed and will become mandatory, within the EU, from 20 May 2020.

Given the detail, provided in MEDDEV 2.7/1 rev 4, concerning the requirements for equivalence protocols the resulting protocol, for any device, becomes inevitable. It is not as if there is a choice on what aspects are to be compared or on how they should be compared. The requirements are laid out in such a manner that only one protocol, for any measurement technology, should emerge. (Devices that include different types of measurements should have separate equivalence protocols for each. This allows, for instance, for technologies that are provided in both separate and hybrid devices.)

Though detailed in nature, at its heart is a very simple hypotheses that if two devices are marketed as being different, then they are clearly different in some way. Therefore, for equivalence to be proven, it must be proven that the differences have nothing whatsoever to do with technical, clinical or biological aspects of measurement. If the difference is just a rebranding, it should be simple to prove, but it still needs to be proven.

While sunset clause in the universal protocol can cover existing validations, there is no way to cover existing equivalences. Furthermore, for every blood pressure measurement technology developed, there are dozens of different devices that use this technology. The original manufacturers often have several devices aimed at different groups and these can be provided in different languages or even, in some counties, under different brands. When it comes to OEM versions, some devices are sold under several brands or the housing may be changed to suit a particular style. Under the new regulations each and every one of these must undergo either a new validation or an equivalence.

While, on the one hand, this may seem onerous, the new regulations should be recognised as hugely advantageous for both manufacturers and consumers. Families of devices become defined by sets of devices where equivalence can be proven for every pair of devices in the set. In these instances, the results of the validation of any device within a family will apply to all devices in the family, since that device is equivalent individually to all other devices in the family. It, therefore, becomes much more practicable to have multiple validations, with different cuffs and on different populations, and the result can be applied to all equivalent devices. All manufacturers have to do is set out all of the device features on the Medaval Registration Form that was designed specifically for equivalence comparison. Any two devices can be compared, the differences shown and equivalence either proven or disproven.

Equivalence is considered as a scientific study, subject to hypotheses testing and rigorous analysis, as for any validation study. Equivalences sought will be checked and reviewed scientifically as for any scientific study. A detailed report will be provided to manufacturers and results, excluding details of sensitive material, will be published providing consumers with evidence of equivalence and of differences.

We need to make it so simple and easy for genuine manufacturers. This does not mean that there is any compromise on the science or the scrutiny. At all stages, this has to be performed on the belief that the devices are not equivalent, as it is the rejection of that hypothesis that proves equivalence. It is only when one is forced to reject that hypothesis that equivalence is proven. However, from a manufacturer perspective, this should become part of a standard routine whenever a new device is being marketed.

While details of the implementation of the regulations have yet to be completed and published, it is important that manufacturers become aware of and are encouraged to begin implantation of compliant equivalence as soon as possible. The benefits to both them and consumers will be evident from immediately and devices will become regulation compliant seamlessly.

Medaval has already initiated contact with regularity authorities regarding the implantation of the regulations. The company is in an ideal position to assist manufacturers in ensuring that all of their devices will be compliant.

The Need for (EU) 2017/745

Fake Validations

There are now, numerous sites that purport to provide “best” and “top” lists of monitors but are really just advertising sites for Amazon and some other marketing sites. Many of these contend to perform their own “validations” but which are statistically useless. Furthermore, many of the brands listed are, when examined, untraceable. Yet they are presented as reliable brands with “Clinically Validated” devices, often with accompanying FDA and other approvals, and several positive fake reviews. A few big names (usually Omron) are included in the list to make it seem legitimate but the real target devices are the brands promoted as being equally reliable but far cheaper and, therefore, best value and, of course, best buy.

Contact information is often completely unavailable or Chinese-phonetics drivel. A search on Google maps, where addresses are provided, leads generally to a private residence. For example, Figure 1 shows the manufacturer address for the Ourlink brand (source Google Maps). Companies appear for a while and vanish but are replaced by new ones. They can advertise what they want; the devices are “dirt cheap”, so it is not worthwhile chasing up if they don’t work and, even if someone is harmed, they cannot be traced anyway. This isn’t an odd isolated case – this is now the norm. Even organisations whose logos are used incorrectly cannot do anything about it.

All of this is legal. Independent validation and proof of equivalence is not required. The devices sold can probably be best described as “harmless”, at least in terms of mechanical safety. They do not have to conform to anything more than would be required of a toy.

Confusing for the Customer

From most lay consumers’ perspectives, and probably those of many more professional consumers than we would hope, an approval or recommendation by a known body is assumed to mean a fully validated device. Terms like “Clinically Validated” are advertised, knowing that they are inferred as meaning a proper validation and that few ever try to see what they mean. In most cases, no explanation is provided at all.

Regulations usually require that at least one “FDA”, “ISO”, “CE” symbol is provided but few check to see exactly which regulations are applied. This information is often only included in a manual for which purchase is required.

Many devices are sold without a model number or even a name – merely described generically as “Upper Arm” or “Wrist”. After a period these can be replaced with a different device, also “Upper Arm” or “Wrist”.

Even when names and model numbers are provided, they are often reused when models are preplaced by a new generation or even to different concurrent devices. Medaval has had to attach a “(v1)”, “(v2)” to many devices to provide some method of distinguishing them. The information can also be omitted in validations and it can be impossible to know to which device the validation applies.

Inconsistency from Experts

There is no consistent direction, as to where to find reliable information. Medaval, BIHS, DHL, Hypertension Canada, the ESH and others all offer different lists [8-12]. These are difficult and very time-consuming to construct and to keep up to date and correct. The same devices can appear differently on different lists or are shown as separate devices for different cuff validations.

The problem is illustrated in the recent list of devices published on behalf of the ESH [12], was compiled from the Medaval, BIHS and published version of the DHL list [13]. Despite the effort, the list contains no less than 56 mistakes, ranging from incorrect device names, duplications and non-existent devices to unproven validations and equivalences. Many of these are mistakes made at the source but were carried on to print.

The BIHS is cited as a source for validated devices for this list. Yet the BIHS do not publish internal validations and they apply equivalence to “derivatives”, simply on the say-so of the manufacturers. [9] The term is defined in the statement “Devices that are listed as being derivative of other models have been approved for addition to these lists on the basis of information supplied to the BIHS by the manufacturer. This information has not been rigorously tested but has been accepted in good faith.”

The German Hypertension League put huge emphasis on the their quality seal but yet they do not publish internal validations and apply equivalence to devices described as “baugleich” (structurally identical or identical in construction) [10]. The term is defined in the statement “Die mit „ÄP“ gekennzeichneten Geräte sind baugleich mit einem bereits zu einem früheren Zeitpunkt getesteten Messgerät” (Thedevices labelled “ÄP” are structurally identical to a previously tested meter). They do not provide any information on how or to which devices it is applied.

Hypertension Canada recommend 38 devices, according to a gold or silver rating, from seven brands with links to respective sellers [11]. The terms are defined in the statement “Those with a Gold rating meet the highest and most current international standards, and those with the Silver ratings meet the highest international standards available prior to their most recent updates. Both Gold and Silver levels are accepted as accurate”. There is no explanation as to which of “various standards” are used and no proofs are provided. As regards the silver rating, it is unclear whether “prior to their most recent updates”, refers to the devices or to the standards. Validation publications are available for only four of the devices listed.

It is extremely unfair to manufacturers to have such a confusing and inconsistent set of criteria. It is little wonder that many have just not bothered.

The Grand Alignment

As is often the case in history, there is a time when order rises out of chaos and the timing of (EU) 2017/745 could hardly be better.

It echoes loudly the calls by Eoin O’Brien and George Stergiou and those in the EHL policy statement of 2016. [2, 3].

The agreement and publication of the consensus document on a universal protocol provides a platform to publish the protocol for implementation to coincide with the implementation of the regulations.

A protocol for equivalence of blood pressure monitors, according to MEDDEV 2.7/1 rev 4, which will satisfy the requirements has already been written.

The EU is leading the world as regards device regulation and putting validation and equivalence at the level of importance that is needed.

Blood pressure monitor validation is far ahead of other devices in this regards and, the new protocols will provide clarity for all manufacturers.

Already manufacturers can be given guidance regarding equivalence. There is no reason why the manufacturers who wish to be compliant cannot proceed immediately. There is no dependence on validations – they apply after equivalence is proven.

By encouraging genuine manufacturers, fake manufacturers will be far clearer to consumers even before the regulations come into force. There is no reason to wait for another two years.

Once these regulations are in place, like the universal protocol, there should be call for other countries to follow suit. In particular it will become important for the US, Britain, Canada and Australia to join the EU. These, along with the EU, will bring in many other countries who adopt their regulations – effectively making it not worthwhile to have devices that do not comply.

Figure 1

This is an image of the registered address for Ourlink. The Image was taken from Goole Maps Streetview on 28th May 2018.

References

  1. The European Parliament and the Council of the European Union. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance). Official Journal of the European Union. 2017 May 05;60(L 117):1-175. Available from: eur-lex.europa.eu.
  2. O’Brien E, Stergiou GS. The pursuit of accurate blood pressure measurement: A 35-year travail. J Clin Hypertens (Greenwich).2017 Aug;19(8):746-52. doi: 10.1111/jch.13005. Epub 2017 Apr 21. PMID: 28429879.
  3. Campbell NR, Gelfer M, Stergiou GS, Alpert BS, Myers MG, Rakotz MK, Padwal R, Schutte AE, O’Brien E, Lackland DT, Niebylski ML, Nilsson PM, Redburn KA, Zhang XH, Burrell L, Horiuchi M, Poulter NR, Prabhakaran D, Ramirez AJ, Schiffrin EL, Touyz RM, Wang JG, Weber MA. A Call to Regulate Manufacture and Marketing of Blood Pressure Devices and Cuffs: A Position Statement From the World Hypertension League, International Society of Hypertension and Supporting Hypertension Organizations. J Clin Hypertens (Greenwich). 2016 May;18(5):378-80. doi: 10.1111/jch.12782. Epub 2016 Feb 8. PMID: 26852890.
  4. Stergiou GS, Alpert B, Mieke S, Asmar R, Atkins N, Eckert S, Frick G, Friedman B, Graßl T, Ichikawa T, Ioannidis JP, Lacy P, McManus R, Murray A, Myers M, Palatini P, Parati G, Quinn D, Sarkis J, Shennan A, Usuda T, Wang J, Wu CO, O’Brien E. A Universal Standard for the Validation of Blood Pressure Measuring Devices: Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Collaboration Statement. Hypertension. 2018 Mar;71 (3):368-374. doi: 10.1161/HYPERTENSIONAHA.117.10237. Epub 2018 Jan 31. PMID: 29386350.
  5. Stergiou GS, Alpert B, Mieke S, Asmar R, Atkins N, Eckert S, Frick G, Friedman B, Graßl T, Ichikawa T, Ioannidis JP, Lacy P, McManus R, Murray A, Myers M, Palatini P, Parati G, Quinn D, Sarkis J, Shennan A, Usuda T, Wang J, Wu CO, O’Brien E. A universal standard for the validation of blood pressure measuring devices: Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Collaboration Statement. J Hypertens. 2018 Mar;36 (3):472-8. doi: 10.1097/HJH.0000000000001634. PMID: 29384983.
  6. Stergiou GS, Karpettas N, Atkins N, O’Brien E. European Society of Hypertension International Protocol for the validation of blood pressure monitors: a critical review of its application and rationale for revision. Blood Press Monit. 2010;15(1):39-48. doi: 10.1097/MBP.0b013e3283360eaf. PMID: 20087174.
  7. European Commission – Health technology and Cosmetics. MEDDEV 2.7/1 rev.4: Guidelines on Medical Devices – Clinical Evaluation: A Guide for Manufacturers and Notified Bodies under Directives 93/42/EEC and 90/385/EEC. Brussels, Belgium: European Commission; June 2016 (65 p). Available from: http://ec.europa.eu/DocsRoom/documents/17522/attachments/1/translations/.
  8. Medaval Ltd. Blood Pressure Monitor Registry. [Internet] Dublin, Ireland: Medaval; 2018. http://medaval.ie/device-category/blood-pressure-monitors. Accessed 2018 May 29.
  9. British and Irish Hypertension Society. BP monitors, Derivative Devices. [Internet] Leicester, UK: BIHS; 2017/2018. https://bihsoc.org/bp-monitors/. Accessed 2018 May 28.
  10. Deutsche Hochdruckliga eV DHL. Geprüfte Messgeräte 2001-2017. [Internet] Heidelberg, Deutschland: DHL; 2018 Apr 28. https://www.hochdruckliga.de/messgeraete-mit-pruefsiegel.html. Accessed 2018 May 21.
  11. Hypertension Canada. Blood Pressure Devices Recommended by Hypertension Canada. [Internet] Markham, Ontario, Canada: Hypertension Canada; 2018. https://hypertension.ca/hypertension-and-you/managing-hypertension/measuring-blood-pressure/devices/. Accessed 2018 May 30.
  12. Stergiou GS, Asmar R, Myers M, Palatini P, Parati G, Shennan A, Wang J, O’Brien E; European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. Improving the accuracy of blood pressure measurement: the influence of the European Society of Hypertension International Protocol (ESH-IP) for the validation of blood pressure measuring devices and future perspectives. J Hypertens. 2018 Mar;36(3):479-87. doi: 10.1097/HJH.0000000000001635. PMID: 29384984.
  13. Tholl U, Lüders S, Bramlage P, Dechend R, Eckert S, Mengden T, Nürnberger J, Sanner B, Anlauf M. The German Hypertension League (Deutsche Hochdruckliga) Quality Seal Protocol for blood pressure-measuring devices: 15-year experience and results from 105 devices for home blood pressure control. Blood Press Monit. 2016 Aug;21(4):197-205. doi: 10.1097/MBP.0000000000000186. PMID: 26998590.