The health care products giant Johnson & Johnson continued to market an artificial hip in Europe and elsewhere overseas after the Food and Drug Administration rejected its sale in the United States based on a review of company safety studies
During that period, the company also continued to sell in this country a related model, which earlier went on the market using a regulatory loophole that did not require a similar safety review. It is not known how many people overseas received the replacement hip after the agency decided in 2009 not to approve it, nor the number who received the closely linked implant sold in this country. During some eight years on the market, the two implants were used in about 93,000 patients worldwide, about one-third of them in the United States. Both models were based on the same component, an all-metal hip socket cup that experts say was faulty in design. The DePuy orthopedic division of Johnson & Johnson, citing declining sales, began phasing out both models of the device — formally known as an articular surface replacement device, which DePuy marketed under the name ASR — in November 2009 and formally recalled them in August 2010 amid reports in databases of orthopedic patients abroad showing they were failing prematurely at high rates. But in a confidential letter, the F.D.A. told Johnson & Johnson in August 2009 that company studies and clinical data submitted to gain approval in the United States to sell the model available overseas were inadequate to determine the implant’s safety and effectiveness, according to a summary of the letter reviewed by The New York Times. The agency also told the company it would need added clinical data to pursue the application, a process that would probably have taken a year or more. DePuy’s receipt of the notice came as regulators and surgeons abroad as well as doctors in this country were raising serious questions about growing failures of both models of the implant. A spokeswoman for DePuy confirmed that the company had received the agency’s so-called nonapproval letter. But the spokeswoman, Mindy Tinsley, declined to release the letter or to respond to questions about when, or if, DePuy disclosed the ruling to doctors, patients, investors or regulators abroad. A principal researcher on the clinical studies submitted by the company to the F.D.A. said he was not informed of the agency’s decision. Also, a review of publicly available information indicates that the company did not discuss the agency’s nonapproval letter in financial reports or in presentations to analysts while the device remained on the market. There is no suggestion that Johnson & Johnson broke the law. Regulatory standards in other countries, like those in Europe, for approving the sale of medical devices are typically lower than here. A spokeswoman for a British regulatory agency, the Medicines and Healthcare Products Regulatory Agency, said that companies like Johnson & Johnson were not required to notify it when the F.D.A. refused to approve a product that was used in patients there. However, the F.D.A.’s rejection may further deepen the company’s legal and financial problems surrounding the ASR. Last month, the company took a special $3 billion charge, much of it related to anticipated legal and medical expenses associated with the recall. An estimated 5,000 lawsuits involving the device are pending, including some from patients crippled by tiny particles of metallic debris shed by the implants. William Vodra, a lawyer who specializes in F.D.A. regulation, said that, in general, drug and medical device makers typically disclose nonapproval letters if they might have a material impact on a company’s finances. Mr. Vodra added that apart from that financial calculation, there was no hard-and-fast rule about making such rulings public. Mr. Vodra said that if a company decided to withhold a nonapproval letter that contained important safety information about a device used by doctors, it could face damage to its brand. “They have to think long and hard of the reputational impact,” he said. The handling of the ASR highlights how the F.D.A., by keeping its approval process confidential, may affect the health and safety of patients. An agency spokesman, Morgan Liscinsky, declined to disclose the letter on the ASR, saying the agency had a policy of not releasing such notices because they might contain confidential business information. The version of the ASR rejected by the agency was developed by DePuy for use in a hip replacement procedure called resurfacing, which is a bone-sparing alternative to standard surgery. DePuy started selling the implant abroad around 2003. But because resurfacing was a new procedure, the agency required the company to run clinical trials before selling the device here. In 2005, while those studies were under way, DePuy used a less rigorous regulatory pathway to win F.D.A. clearance to sell a version of the ASR based on the same metal hip cup for use in traditional joint replacement surgery. Because that version resembled hip implants already on the market, the agency was authorized to clear it for sale without clinical testing. It was apparently within weeks of getting the F.D.A. letter in August 2009 that DePuy executives began a strategy to slowly phase out ASR sales while shifting surgeons to other company implants. Three months after the letter, in November 2009, the company publicly announced its decision to phase out the ASR, attributing the move to declining sales. The company also said then that it had withdrawn its F.D.A. application for the resurfacing version of the device. In a statement, Ms. Tinsley, the DePuy spokeswoman, said the company “weighed the additional data that would be required for approval against the declining market demand for hip resurfacing.” It is not known precisely what the agency’s letter stated nor is it clear how, or if, the agency’s concerns about the resurfacing version of the hip implant applied to the model used in this country in standard replacement surgeries. The agency can reject approving a device for various reasons, including cases where it is seeking only small amount of added data. Copies of the letter that might have been provided to lawyers involved in litigation against Johnson & Johnson have been sealed by the court. But the summary of the letter to DePuy suggests that it was long and detailed — 13 pages in all. Before the recall, DePuy long defended the articular surface replacement device, saying that any failures associated with it reflected failures by surgeons to properly implant the hip cup. The surgeons who performed the study of the resurfacing version of the device that was rejected by the F.D.A. were handpicked by DePuy and included the model’s designers. Dr. Antoni Nargol, an orthopedic surgeon in England who worked on the study that DePuy submitted to the F.D.A. and later became a critic of the device, said in a telephone interview that the company had never informed him that its application for approval in the United States had been rejected. In March 2010, The Times disclosed that F.D.A. records showed that the agency had received 300 complaints about the ASR, virtually all of them involving patients who had to undergo replacement operation just a few years after getting the device. That number has since reached into the thousands. DePuy continued to insist then that it was safe, but in August 2010, after data in a British registry of orthopedic patients showed high failure rates for the ASR, the company recalled both versions of the device.