A new report by the FDA highlights weaknesses in medical device quality in the US over the past decade.

The FDA’s report, Understanding Barriers to Medical Device Quality, stated that while revenues in the medical technology industry have grown over the last ten years, “serious adverse events” have outpaced this growth by 8% each year.

Failures in medical device design and manufacturing process control were found to account for more than half of all product recalls.

“While medical device flaws may vary by device, some sources of error are pervasive throughout the field,” the report reads.

“Identifying and addressing systemic barriers may yield improvements in medical device quality on a large scale.”

The report was launched by the FDA’s Center for Devices and Radiological Health in order to understand and improve gaps in device quality, and outlines recommendations for both industry and federal regulators.

The analysis found that “nearly 60% of the adverse event reports” involved cardiovascular, in vitro diagnostics and general hospital/surgical equipment.

“Our efforts revealed that there are systemic gaps within the medical device industry's quality approach that result in these issues,” said the report. “Attempts to improve quality are hindered by challenges within the industry as well as specific aspects of the agency's regulatory approach.”

According to the FDA, medtech manufacturers are facing a series of challenges which are impeding device quality, such as the increasing complexity of devices, time to market competition, and cost pressures.

Identified opportunities for improvement include postproduction monitoring and feedback, creating quality incentives, and improving design and engineering.

The report also cited steps for the FDA to incorporate, such as clarifying Agency requirements and learning from regulators of similar high-tech industries.

A similar initiative is underway in Europe to improve medical device regulatory assessment processes, with support from Eucomed.

What level of medical device failure is acceptable? Brad Abbey argues that the industry needs to arm itself against the threat of litigation – not with lawyers, but with the right kind of evidence.

I was somewhat taken aback by a letter in the British Medical Journal last December, where under the unlikely-sounding title ‘FDA is gold standard of review’, Mark B. Leahy, president and CEO of the US Medical Device Manufacturers Association, while singing the praises of the industry, said that a recent study of FDA-approved medical devices from the past 5 years showed that fewer than 1% had been recalled.

Most recalls, he said, were due to manufacturing and design problems in a post-marketing setting. This was in response to an article that had been highly critical of the safety surveillance of medical devices in the US and the low hurdles that have to be jumped to get a device approved (seemingly true on both sides of the Atlantic).

I am a generalist in the healthcare industry, mainly involved with medicines, but to say I was surprised by that figure is an understatement. I realise that the number of car recalls may be higher – but with a surgically implanted device, the owner cannot check it in at the service centre and pick it up at the end of the day.

I know that MHRA gives daily warnings about medical devices, from wheelchairs to drug-eluting stents; but given that the level of adverse event risk that is acceptable to the public for a medicine is somewhere between 1 in 10,000 and 1 in 100,000, the 1% risk seems difficult to accept.

A lead article in the May 2011 BMJ, by Peter Wilmshurst of STARFlex fame, opened with the comment that the regulation of medical devices is (in his opinion) unsatisfactory, unscientific and in need of a major overhaul. Pretty damning stuff.

 

Duty of care

The registration of medicines requires data on the safety, efficacy and quality of products, and the numbers of patients needed to demonstrate an acceptable risk/benefit profile can be dauntingly high. The same level of scrutiny does not happen in Europe for medical devices, where a single approval can trigger cross-community acceptance.

With the increasing complexity of devices and the high levels of patient expectation, it is hardly surprising that when seemingly good devices go wrong the patients want compensation – and, where there is a suitable arena, for punishment to be meted out.

In the US, where many complex medical devices are developed and initially marketed, the ‘learned intermediary’ doctrine has been used by healthcare product manufacturers in recent times to protect themselves in the event of something going wrong. This doctrine, used in the US legal system, states that the manufacturer of a product has fulfilled their duty of care when they provide all the necessary information to a ‘learned intermediary’, who then interacts with the consumer.

This doctrine has been used primarily by pharmaceutical and medical device manufacturers in defence against tort suits. In a majority of American states, the courts have accepted this as a liability shield for pharmaceutical companies.

However, drug and medical device manufacturers sustained an unexpected blow in August 2008 in Rimbert v Eli Lilly and Company: in a federal court decision, for the first time, there was a rejection of the learned intermediary doctrine in its entirety. The decision rejected the notion that the manufacturers of drugs and medical devices do not have to make the patient fully aware of the risks associated with them and that this can be delegated to the prescriber.

The idea underlying the ‘learned intermediary’ doctrine is that the prescriber, who has expert knowledge and skill, should make the decision about risk. But changes in the consumer environment whereby prescription products can be advertised directly to potential patients have rendered this justification obsolete, and so it was predictable that for medical devices – some of them traditionally never coming ‘into the hands’ of the patient – the risk scenario would be influenced by the lesser amount of risk/benefit information needed before approval for marketing. While the doctrine has not been used in Europe, the risk information relating to devices is lagging behind that for medicines.

In order to be vigilant about the risks of medical devices, companies will be best served by surveillance systems that monitor the risk/benefit profile of products from the moment they are first evaluated (even if that takes place in animal models). This is not always easy.

A letter in the BMJ (in the same issue as Leahy’s letter) from a Welsh group of doctors highlights the problems of post-marketing surveillance for medical instruments, and in particular the use of single-use devices for tonsillectomy from 2001 in the wake of the variant Creuzfeldt-Jakob disease that followed the ‘mad cow’ scare of the 1990s.

Widespread adverse events were associated with these non-reusable instruments despite their CE marking, and they were deemed not fit for purpose. The case for reform of medical device regulation therefore seems a given.

 

Hip or lame?

In the meantime it seems that the visible portion of the iceberg of device regulation-related problems is giving rise to a stream of litigation that could possibly become a tide. Recent Medtech Business news reports have followed the fate of orthopaedic company DePuy and its ASR hip replacement.

Hip replacement is one of the clinical successes of the marriage between orthopaedic surgeons and the medical device industry, and it was estimated (before this year’s NHS rationing) that about 70,000 patients were undergoing total hip replacement each year in the UK.

I remember metal-on-metal hip replacements from the 1970s (I have one in a drawer at home that came to me as a result of its breaking), and they became popular again in the 1990s. However, the most recent generation have not fared so well, with higher than expected rates of failure and concerns about excessive levels of metal ions (cobalt and chromium) in the blood of patients.

According to 2010 data from the National Joint Registry of England and Wales, the DePuy ASR Hip Resurfacing System has a revision rate of 12% at 5 years after surgery and the DePuy ASR XL Acetabular System has a revision rate of 13%.

That means that during the first 5 years after a hip replacement with the DePuy ASR hip, at least 1 in 8 patients will experience hip failure requiring painful and expensive revision surgery. With more than 90,000 DePuy ASR hips in patients worldwide, over 11,000 people could require additional surgery due to the defective design of this implant and DePuy’s failure to remove it from the market earlier.

One of the questions that remains unanswered was whether there were potential conflicts of interest between the supplier and the healthcare professionals who developed and were involved in promoting these devices. The key issue in litigants’ minds is that the device did not perform as well as such a device might be expected to, and it seems that the device’s registration in the US was obtained without clinical trials to prove its long-term safety and efficacy. In a litigious society such as the US, where someone must pay for any mistake, the supplier appears to have suffered with the rolling of heads and the decision to remove the offending brand from the market.

Don’t get the idea that this case is a one-off: the recent history of medical devices suggests that arrivals on the market may sometimes be premature, as real risks may not have become apparent. Whether this is related to inappropriate endorsements from the medical profession is difficult to judge, but there are known examples of high-level payments to medical inventors who ‘sell’ their developments to industry and subsequently endorse them.

On the other hand, everyone is aware of what happened to Peter Wilmshurst when he took the opposite stance against a device manufacturer: there was a serious attempt to punish his critical views (which seemed to be well founded) and personally break him through the English court system.

 

Evidence is strength

Litigation against medical device companies is nothing new. However, in an age when people with problems can readily find lawyers willing to take on their problems, and some lawyers (particularly in the US) go looking for people who did not even know they had problems, access to litigation seems to be easier – and it is oiled by the possibility of compensation (which may be deserved when devices turn out to be inadequate or unsafe).

A Google search for the term ‘medical device litigation’ returned 640,000 hits; most of the leading ones were to do with lawyers offering their services in the pursuit of such litigation, or training sessions for lawyers who want to become involved in such cases, or training for companies who want to avoid them. I don’t believe a wake-up call about the risks of being sued is necessary, but what is well worth thinking about is the possible root causes of the current danger, which can ruin a company that believed it had a good product.

The message I am offering is consistent. The products of the healthcare industry must be subject to close and continuous scrutiny for their risk/benefit profile, and this should be done prior to marketing and continue in a structured manner post-marketing. NICE advisory policy on the best devices to use is still in its early stages.

There seems to be a raft of opinion supporting the idea that the regulation of medical devices (in Europe, and probably also in the US) needs to be overhauled to eliminate the placing of devices on the market with inadequate safety and efficacy monitoring.

Rather than finding ways of avoiding expenditure during a product’s development and launch by minimising the collection of such data, companies need to embrace the need for resilient data sets and continual risk/benefit signal monitoring. The competent authorities will wake up to this need, and those with effective systems in place will withstand the culture change best.

Brad Abbey is an industry observer, or the pen-name of an industry observer. The views expressed in this article are those of Brad Abbey, and do not necessarily reflect the views of Medtech Business.

The diversity of wounds and the wounded means that the evidence base for wound care therapies is a complex issue. Professor Richard White of the University of Worcester and Wound Care Alliance UK looks at how companies can best establish the case for their products.

The current situation regarding issues of product evidence and product availability in wound care has been discussed in Medtech Business (May and June 2010). Therapies affected by these issues include silver and other modern wound treatments, such as moist wound healing dressings and topical negative pressure (TNP) devices, which have attracted the scrutiny of those who conduct systematic evidence reviews. Following those commentaries, this article offers some proposals for a way forward.

Therapies on trial

The modern age in wound care, dating from around 1970, has seen a variety of new medical devices come to market – many of which have achieved ‘standard of care’ status. For example, elastic and non-elastic compression bandaging; hydrocolloid, alginate, foam and film dressings; honey as a CE Marked product and many others have become established in the clinical armamentarium.

Countless clinicians, many of them acknowledged experts, have come to rely on these products, knowing that when they are correctly used they work well. This steady supply of products has come from an innovative, dynamic industry that works closely with the clinician.

However, the evidence gathered to support these products does not satisfy the various groups who insist on the Cochrane-style analysis of randomised clinical trials (RCTs). Recent publications have criticised the evidence for moist wound healing, antiseptic dressings and TNP. This criticism, published in the medical literature and the national press, has led to restrictions on product availability.

The key priority, in my view, should be to maintain a regular flow of safe and effective innovations, supported by sufficient evidence for regulatory purposes and for informing the clinician. The introduction of such products should, of necessity, be followed by the ongoing collection and publication of clinical evidence.

Innovation is vital to wound care, as the steady flow of new and improved products leads directly to better patient care. The discipline is still in its infancy – a stage when developments are frequent. The industry is populated by a broad mix of large, established companies and smaller companies, many of them start-up ventures. This affects the level of investment available for expensive RCTs.

Should trials be left to the wealthy companies alone? Or can other, more economical forms of clinical evidence be gathered instead? That would offer the smaller, less affluent companies greater opportunity to develop products, gather evidence and take their treatments to market – and in the past, that has been a significant feature of wound care in the UK.

There is no doubt that evidence in one form or another is essential for the development of wound care – so open discussion of the issues around what makes for effective evidence is needed. In addition, some proactive action on the part of the wound care sector is also essential: companies must, to my mind, take action before further restrictions in product availability are foisted upon them.

Finding the facts

There is a strong case for looking more carefully at what evidence is already available in the public domain. Cochrane analyses have been justly criticised for not taking all of the available evidence into consideration. A preferable method of analysis, with recommendations, is the GRADE system. This well-known and respected system, in my opinion, should be employed to assess the evidence for a number of existing products.

With regard to the ‘quality’ of different types of evidence, the European Wound Management Association (EWMA) has published guidelines for the conduct of RCTs in the May 2011 issue of the Journal of Wound Care.

If a company decides that an RCT is the most appropriate means of gathering clinical evidence, it is important that they avoid the pitfalls which have blighted many previous trials. The Cochrane reviews list the numerous shortcomings in trials, mainly methodological errors, which form grounds for disqualification. These can be avoided!

• At the planning stage, trials should be configured with purchasers in mind: as well as gathering clinical information, the trial should take account of economic factors and quality of life instruments.
• Once the data are published, these should enhance the chances of product uptake or changes in clinical practice. Quality data will make counter-arguments difficult and merit publication in quality journals, and so garner support from opinion leaders.

Case studies are frequently used to provide support for products. However, it is an unfortunate fact that many, probably most, of these studies are of very little value. This is due to their planning and objectives, as well as the information provided. When case study posters and journal reports make products appear to be panaceas, it is no wonder that the whole exercise becomes devalued.

Cohort studies, when properly conducted, can be valuable in many ways. Their merit has been extolled by many influential figures. The GRADE system of analysis gives reasonable weighting to such studies, whereas Cochrane analyses ignore them completely. Their format is less clear than that of RCTs – but when they are conducted in a multicentre setting, with clear objectives and endpoints such as clinical goals, economic factors and quality of life issues, they provide useful data.

Post-marketing surveillance studies, conducted long-term in the ‘real world’ of routine clinical practice, are under-used and under-estimated in wound care. As far as I am aware, they are mandatory in Germany and some quality data have been published from these studies.

Audit of clinical practice is as ‘real world’ as we can get when it comes to clinical (and hopefully financial) data. Efficient clinical settings can audit their practice for long-term outcomes in treatment of wounds. Such studies can provide the most meaningful evidence.

Value and cost

Cost-effectiveness, or health economics, has been a high priority in healthcare for many years, yet it does not figure in enough wound studies. Rather naively, claims of ‘cost-effective’ based on the unit price of a product still appear.

Health economics is a defined and refined science and must be recognised, and used, as such. In this respect there is vast room for improvement in company-sponsored wound treatment studies.

For the future, it is important that the evidence for wound care therapies is of better quality than it generally has been over recent decades. This is achievable through awareness of the literature and close liaison with experts – it does not necessarily need to incur substantially greater costs!

The whole dynamic of selling has changed over the past twenty years. No longer is it sufficient to demonstrate the product to a nurse or doctor and wait for the orders to flow in. Other key groups are now involved, and liaison with them to facilitate product uptake has become essential.

Everyone involved in wound care in the UK must now be aware of, and recognise the important role of, pharmacists, medicines management, formulary committees etc. Companies must do more to involve these groups.

The transition or evolution of standards for medical devices from the days of the first modern ‘moist wound dressings’ is remarkable. Following the enactment of the Medical Device Directives in the mid-1990s, the system has become more ordered and bureaucratic.

However, this process is far from complete. The recent furore over failing hip implants has shown that the current regulations are not adequate to prevent major clinical catastrophes involving medical devices. In the USA, the FDA is taking a very close look at device regulation.

As the standards for evidence become more sophisticated, better reflecting the realities of clinical practice, the medical device industry – and in particular, the sector supplying wound dressings and associated products – has the opportunity to address the need for change and adapt accordingly.

 

 

Richard White is Professor of Tissue Viability at the University of Worcester.