Opinion ID: 1211810
Heading Depth: 2
Heading Rank: 1

Heading: Pre-FDA Approval and the VIGOR Study (1996-March 2000)

Text: Prior to the FDA's approval of Vioxx, officials at Merck were concerned that Vioxx could cause harmful cardiovascular (CV) events, such as heart attacks. Internal emails from 1996 and 1997 demonstrate that Merck employees were aware that there was a substantial chance and a possibility of CV events that could kill [the] drug. App. at 496. In 1998, an unpublished internal Merck clinical trial entitled Study 090 revealed that Vioxx caused a greater incidence of CV events than a placebo or a different arthritis drug. [2] In January 1999, Merck commenced the VIOXX Gastrointestinal Outcomes Research (VIGOR) study, which compared Vioxx to naproxen, the active ingredient in brand-name pain relievers such as Aleve and Naprosyn. [3] Although the study showed that Vioxx had a GI safety profile superior to that of naproxen, it also showed that Vioxx users had a higher incidence of CV events than naproxen users. In a March 9, 2000 email, defendant Edward Scolnick, the President of Merck Research Laboratories, acknowledged the existence of CV events, commenting, it is a shame but it is a low incidence and it is mechanism based as we worried it was. App. at 512. Merck did not attempt to conceal the results of the VIGOR study. It made them public in a press release on March 27, 2000, that emphasized Vioxx's superior GI safety profile but also noted the incidence of CV events. Merck stated: [S]ignificantly fewer thromboembolic events were observed in patients taking naproxen in this GI outcomes study, which is consistent with naproxen's ability to block platelet aggregation. This effect on these events had not been observed previously in any clinical studies for naproxen. Vioxx, like all COX-2 selective medicines, does not block platelet aggregation and therefore would not be expected to have similar effects. App. at 765. The press release also stated that [a]n extensive review of safety data from all other completed and ongoing clinical trials, as well as the post-marketing experience with Vioxx, showed no indication of a difference in the incidence of thromboembolic events between Vioxx, placebo and comparator NSAIDs. App. at 766. The VIGOR study results were widely reported in the press, medical journals, and securities analyst reports. Market analysts and members of the press immediately understood that CV events could be a side effect of Vioxx. Nonetheless, many observers also took notice of Merck's hypothesis that naproxen lowered CV events (the naproxen hypothesis). The naproxen hypothesis attributed the results of the VIGOR study to the beneficial effects of naproxen's blocking of platelet aggregation rather than to the harmful effects of Vioxx in causing thromboembolic events. The issue whether naproxen lowered the heart attack risk or Vioxx caused it was thus presented. While many analysts noted that the naproxen hypothesis was unproven, some also concluded that it was the most likely explanation for the increased CV events observed in the VIGOR study. One representative article distributed by Reuters on April 27, 2000, quoted a Merck spokesman who acknowledged the statistically significant finding that patients of Vioxx had a higher rate of CV events, but suggested that this might be explained by a beneficial effect of naproxen. App. at 2287. In that same article, however, a spokesperson for the manufacturer of Naprosyn explained that the company had no knowledge that naproxen prevented heart attacks or strokes; similarly, an analyst for ABN Amro suggested that he was skeptical of Merck's explanation.