Major cardiac implants categories.

This study analyzes different cardiac implants categories; the focus is made on the following four major cardiac implants categories:

• An ‘Implantable Cardioverter Defibrillator (ICD)’ is an implant placed under the collarbone. It can detect dangerous arrhythmias, and respond with an electrical signal to restore a normal rhythm [7].
• A pacemaker is also implanted under the collarbone. A lead is placed from the device to the inside of the ventricle wall to keep the heart beating regularly [8].
• Cardiac Resynchronization Therapy (CRT), which is also implanted under the collarbone, has three leads and can sense dangerous arrhythmia, and then deliver a pulse to correct the rhythm back to normal. CRT has either ICDs or pacemaker inside, so it is called either CRT-ICDs or CRT-Pacemaker [9].
• A coronary stent is a very small wire mesh tube used to prop open an artery during angioplasty [10].

Definition and classification of medical device recall.

According to the U.S. Food and Drug Administration (FDA), a recall is an action taken to address a problem with a medical device that violates FDA law [11]. Recalls are classified by the FDA to indicate the relative degree of health hazard presented by the product being recalled [12]:

• Class I: will cause serious adverse health consequences or death;
• Class II: may cause temporary or medically reversible adverse health consequences or where the probability of serious adverse health consequences is remote;
• Class III: is not likely to cause adverse health consequences [12].

In addition, in comparison to device regulation centralized at the national level by the FDA in the U.S, the EU provides guidance but directives are interpreted by national Competent Authorities and private Notified Bodies [13]. EU member states use a different recall system to the US FDA system, namely the “Field Safety Corrective Actions”[14]. A “Field Safety Corrective Action” is an action taken by a manufacturer to reduce a risk of death or serious deterioration in the state of health associated with the use of a medical device that is already placed on the market. Such actions, whether associated with direct or indirect harm, should be reported and should be notified via a Field Safety Notice [14].

Implantable cardioverter defibrillator (ICD).

Of all 42 recalled ICD reports, 50% had battery problems, 23.8% had problems related to therapy delivery, and 21.4% were associated with software malfunctions. One report was related to data output express issues, and another report was related to connection issues. Ten out of 21 reported battery problems recalls were due to capacitor issues. The latest recall was mentioned by Medicines and Healthcare Products Regulatory Agency (MHRA) in Sep. 2013, until recall issuing date, 38,500 ICDs and CRT-Ds have been distributed worldwide. The recall reason was due to the accelerated degradation of the capacitors, which in turn depleted the battery at a faster rate, thereby increasing the risk of faulty therapy delivery [18].

Pacemaker.

Of all 15 reported pacemaker recalls, 33.3% involved a software malfunction, 20.0% had battery problems, and 20.0% were associated with therapy delivery inhibition. Two associated with delivering incorrect output data, another two with connection problems. Regarding the software malfunction issue, the latest recall was issued by Swiss Agency for Therapeutic Products (Swissmedic) in Dec. 2012. Approximately 8,200 of such devices have been distributed worldwide until the recall issuing date, and approximately 6,000 of these were estimated to be implanted. The related pacemakers did not provide a change in sensor driven (rate responsive) pacing rates in response to patient’s physical activity [19].

Coronary stent.

15 recalled coronary stent reports were included in this study, whereas all of the recall reasons were associated with ‘therapy delivery problems’. Six reports were due to the fracture of the device; seven reports referred to a partially deployed or failed therapy, and two reports were associated with the inadequate size of the coronary stent. In July 2004, FDA issued two Class I recalls of coronary stents (TAXUS stent and Express² stent). The recall involved approximately 85,000 TAXUS stent systems out of 500,000 in total which have been distributed worldwide until the recall issuing date. Approximately11, 000 Express² stent systems were affected from a total of 600,000 distributed worldwide. The manufacturer received reports of one death and 18 serious injuries associated with the TAXUS stent systems, and two deaths and 25 serious injury reports related to the Express² stent systems[20]. The recall reason was because of the characteristics in both design did not allow the balloon to deflate, which resulted in the impeded removal of the balloon after stent placement [21, 22].

Cardiac resynchronization therapy (CRT).

This review included 13 recall reports of CRTs, whereby nine reports were recalled due to battery issues, two reports were associated with software problems, and two reports with therapy delivery problems. Of all nine reported battery issue reports, six had capacitor malfunctions, and two experienced premature battery depletion. The latest recall was issued by Federal Institute for Drugs AND Medical Devices (BfArM) in Aug. 2013. A total of approximately 264,000 identified devices have been distributed and implanted, especially a subset of 38,500 devices that was manufactured prior to Dec. 2009 and has experienced a higher number of low voltage (LV) capacitor malfunctions. This referred to approximately 0.67% of the overall affected rate; the affected rate of other 225,500 devices was approximately 0.0093%. The reason for the recall was that the manufacturer identified a low voltage (LV) capacitor component in some devices, which may lead to diminished performance after two or more years from the time of implantation [23].

Leads.

A total of ten recall reports associated with the malfunctioning of leads were included in this study. Nine had a recall reason related to connection problems, and one was due to an issue with the fracture of the device. Of the nine cases associated with connection problems, two were due to a separation of wires, five to a lead insulation abrasion, and two others were due to coating materials detaching from guide wires. The latest recall was issued by Swissmedic in Dec. 2012. The manufacturer confirmed 30 reports out of a total 13,500 devices implanted worldwide, where the analysis of the returned leads identified internal insulation breach under the right ventricular (RV) and the Superior Vena Cava (SVC) defibrillation coil electrode, resulting in low pacing impedance, ventricular oversensing and inappropriate therapies[24].

Implantable artificial organs.

Our analysis identified a total of eight reports concerning implantable artificial organs. Three of them were related to inability to provide correct technical feedback data, four had connection problems, and one was due to the inadequate size of the device. The latest recall was issued by Therapeutic Goods Administration (TGA) in Jan. 2014 due to the high potential of implanting oversized valves. The rate of oversized valves occurred at a rate of 0.33%[25].

Weaknesses found in the current cardiac implant recall system.

To ensure patients’ safety in relation to cardiac implants, providing safety information to the public and relevant stakeholders such as patients, relatives, physicians, regulatory authorities, and HTA bodies is a basic requirement. The system for the provision of such safety information warrants further improvement from the current status quo. During the research process we identified that only eleven regulatory authorities provided detailed information regarding recalls in their medical device safety information (including regular updates), which were accessed in English, German or Chinese by the author group. Out of 39countries (34 OECD countries (The Organization for Economic Co-operation and Development)[31]and five BRICs countries (Brazil, Russia, India, China and South Africa)[32]), three regulatory authorities provided English data, additionally to reporting in the local language.

For the purpose of investigating different recall management styles among regulatory authorities, the author group chose one adverse event report, which was reported commonly in seven different regulatory authorities. The chosen recall report refers to the Sprint Fidelis Defibrillator Leads manufactured by Medtronic, which was recalled in Oct. 2007. Table 4 summarizes recall information in details from seven different national regulatory authorities [28, 33–38].

From a comparison of provided information, the following issues can be identified:

• Recall level: all regulatory authorities defined this recall at the highest level of the recall classification.
• Volume and effect: FDA and BfArM provided more detailed information with the number distributed worldwide in total and the local country, also regarding the ratio of defective devices. Other regulatory authorities provided the number distributed in local countries only.
• Only Health Canada (HC-SC) has published that there were five death reports involved in connection to this event.
• All regulatory authorities explained recall reasons and risks related to the affected device.
• Except China Hong Kong Health Department (China HK), all regulatory authorities provided background information on the affected device for stakeholders.
• Contact persons and telephone numbers have been provided for affected stakeholder groups by every regulatory authority.
• Outcome of the event treatment: only MHRA identified the exact date by which the recall had been completed.

Recommendations for the improvement of the safety information provision and management.

In accordance with the results from a study by Kramer et al., referring to limits regarding lack of data on safety outcomes in both US and EU settings, we would like to propose some essential components to be included in a recall report [39]. First of all regarding a unique report name, it is recommended to take the name of recall report from the manufacturing company. This will enable reporting from each regulatory authority according to a unique report name. Secondly, recall reports should highlight the affected product category. Third, the recall issuing date and the deadline for completing withdrawals should be a necessary component of a recall report. This is especially important in the context of indicating the time period of completing the recall, which is missing in most current recall reports. The fourth is that recall classifications should be provided to highlight the risk level of affected devices. It is recommended that each regulatory authority provides a clear description and explanation of their recall classification system. Fifth, providing clear recall reasons and background information can help stakeholders to get a better understanding of the recall situation. Providing information on risk factors is to avoid adverse events occurring in the future in the context of patient safety. The sixth recommendations relates to the volume of affected devices distributed and implanted worldwide and in local countries, for the sake of comprehensive reporting. Seventh, death and injury reports should also be highlighted in the recall reports as a crucial aspect of protecting and ensuring patient safety. The last recommendation refers to the outcome of the recall management including the final effect and completion date, which should be added to recall reporting.

In the study by Kramer et al., it has been reported that the structure of the reporting system in most countries like US, EU, China and Japan is based on recall date of cardiac implants [39]. The use of a centralized reporting system is the current base of the recall system. We propose one additional feature to this useful concept in order to further strengthen reporting. For an improved overview and understanding of recall reasons, an additional product-based recall classification system as shown in the structured analysis is recommended by our author team. The results of this study can be taken as a small scale example of a safety-reporting system. The 103 cardiac implant recall reports analyzed in this study can be sorted into six product categories shown in Fig 2. The cardiac implant recall reasons can be sorted into five categories and 27 sub-categories. When inputting data into the database, it is recommended that under each product category, the recall reasons (plus sub-categories) are highlighted for each recalled medical device, as indicated in Table 2. Based on the product-category to improve a safety-reporting system, the provision of clear information would benefit patients, physicians and researchers and other stakeholder groups in the context of patient safety. For patients, information on recalls is comprehensive and accessible. Such a system could help physicians and patients to make more informed decisions when deciding about diagnosis and treatment measures. For the manufactures and researchers it aids in the analysis and comparison of the recall reasons of each product category, as well as the recall reason ratio.

As highlighted by Silva et al. and his colleague, there is an increasing importance of medical device registry especially registry for pacemaker, meanwhile registries provide re-usable data for researchers and relevant stakeholders [40]. It is recommended to implement implant registries in the context of a post market surveillance system. For example, as of September 2012, there were 38 cardiovascular device registries in the EU [41]. An implant registry is a tool to deliver long-term observational data related to the performance of medical devices, but can also be regarded as an overriding tool when it comes to controlling the high incidence of adverse events[41]. Although registries do not handle recall management per se, they have played an important role in the quick identification of patients, when a recall or adverse event occurred [42]. In addition, registries can survey large populations, providing a powerful scientific method for long-term observational data collection [43]. The authors’ recommendations can provide helpful tools for the use of implant registries in the context of a post market surveillance system. In addition, implant registries can facilitate communication among different stakeholders. For example, within the EU, the European Heart Rhythm Association (EHRA) takes a role in helping to coordinate dialogue among stakeholders. Some unexpected performance of medical devices has been identified early to improve patient safety [44]. A recent development includes plans for a compulsory-nation-wide registry for all medical implants in the Netherlands, based on legal provisions established by the Dutch parliament [45].

In addition to the important issue of patient safety, the consideration of the economic impact of recalls is important. As such, economic losses on the industry and health care payer side can be significant when large numbers of medical devices are recalled. Further, the negative impact resulting from a recall on the reduction of industry market shares needs to be considered. It is estimated that Medtronic’s Fidelis recall cost Medicare (The Official U.S. Government Site for Medicare) some $287 million over five years for monitoring or replacing the leads[46]. Another example that the case of Johnson & Johnson suffering significant losses with a decrease of 7.7% in revenue over the previous year in 2010 because the company had recalled various products due to problems with their quality [47]. Therefore, it is important for manufacturers, insurance companies and the health care system overall to invest in a strong monitoring and surveillance system of medical devices in order to make industry investments more efficient and less risky, in addition to protecting patient safety. Registries play an important role in a strong surveillance system.