Editorials

The saga of Poly Implant Prosthèse breast implants

BMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e306 (Published 11 January 2012) Cite this as: BMJ 2012;344:e306
  1. Carl Heneghan, director, Centre for Evidence Based Medicine 1
  1. 1Department of Primary Care Health Sciences, University of Oxford, Oxford OX1 2ET, UK
  1. carl.heneghan{at}phc.ox.ac.uk

Urgent review of the regulation and postmarketing evidence requirements is needed

Complete and utter confusion now reigns over Poly Implant Prosthèse (PIP) breast implants and what to do, particularly with regard to the evidence needed for their regulation, effectiveness, and, more importantly, safety. Confusion between the European and the American regulatory systems is not helping, and the situation needs radical reform.

The French government has advised 30 000 women to have their implants removed,1 the UK government says they are safe,2 and the United States has never let them on to the market.3 What is going on?

Problems occurred with decision making at the outset. In 1992, the Food and Drug Administration called for a voluntary delay on the use of silicone implants, allowing their use only in the context of clinical trials. This ban remained in place until 2006. In 1996, the FDA sent draft guidance on the types of study needed to demonstrate safety, and later that year PIP implants were cleared for approval under a Section 510(k) review application. Section 510(k) of the Food, Drug, and Cosmetic Act requires device manufacturers to notify the FDA of their intent to market a medical device at least 90 days in advance.4 Between 1996 and 2006, patients with silicone implants were required to be evaluated regularly by their surgeons as part of ongoing clinical trials. However in 2000, because of concerns over complication rates, the FDA ruled that breast implants would require premarket approval (PMA) clearance: a more stringent regulatory evidence requirement. In the same year, the FDA rejected PIP’s application for saline breast implants, citing the fact that the company’s clinical trials did not include sufficient patients followed up for an adequate time to evaluate the device’s safety.

Although the product was CE marked in Europe, in 1991—unbeknown to regulators—the PIP implant went on to differ in two key respects from its original regulatory application: the company dispensed with the protective outer skin and replaced the silicone contents with lower grade material. These changes, which occurred some time in 2001, would require further FDA approval under the Section 510k process, and therefore the lower grade product was not available on the US market.3 But their use in Europe continued until they were banned in the United Kingdom in April 2010, at the same time that the French company was banned from producing and selling PIP implants.

The problems that have occurred with PIP implants highlight several important problems that need to be rectified.

Firstly, closer integration of decision making is warranted. This is underlined by the fact that the US regulator inspected PIP’s French plant in 2000 and sent the company a warning letter about problems with the manufacture of the saline implants, but the French Regulatory Agency reports that it received no such notification. Confusingly French regulators told Reuters, “The FDA wouldn’t be obliged to send it to us if there wasn’t a health risk.”5 Furthermore, CE regulatory data are not available for public scrutiny,6 which makes it easier for second generation devices to deviate from original CE regulatory specifications. Why does the US have a higher regulatory threshold? In contrast to the US system, in Europe medical devices do not need governmental review before they are taken to market and often they do not need to demonstrate effectiveness.3

Secondly, no initial regulatory evidence can safely assume that there will not be harms in the long term, so devices should come with an insurance based funding system to allow for this—companies go bankrupt and harms take a long time to manifest themselves. For example, the FDA states that most patients with breast implants have at least one complication within three years, and as many as one in five women who receive implants for augmentation have to have them removed within 10 years.7 A large cohort meta-analysis of failure data for 9770 implants shows that shell rupture is related directly to implant duration—26% fail at four years, 47% at 10 years, and 69% at 18 years.8

Thirdly, manufacturers cannot be relied on to undertake postmarketing surveillance. This is probably the most damning aspect of the whole saga. Thousands of women enrolled in breast implant studies to evaluate rare complications have simply disappeared. Postmarketing studies, requested by the FDA in 2006, have lost so many of the women they were supposed to follow up that they are unlikely to offer any insight into the long term safety of devices. After three years, a study by Mentor, the maker of Memory Gel implants, lost 79% of the patients enrolled, whereas Allergan, the maker of Natrelle implants, has lost nearly 40% of its participants after two years.9 Current estimates of harm are limited by poor quality data from clinical trials. Only now do we see the emergence of independent registries. These should have been set up at the outset, developed and funded jointly by different countries with inbuilt early warning systems. An alert in one country should be heeded by others.

Fourthly, what have patients been told in the light of insufficient evidence? It seems that many women may have been told breast implants were safe, but this was and is impossible to know. If women consented on the basis that the implants are safe, this is ethically indefensible.

Finally, could this happen again with other medical devices? Certainly, given the problems outlined. Regulation and postmarketing evidence requirements for the most risky devices, which are mainly those implanted in the body, need urgent review. Properly funded and maintained national and regional device registries are also needed immediately.

Notes

Cite this as: BMJ 2012;344:e306

Footnotes

  • Competing interests: The author has completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Commissioned; not externally peer reviewed.

References