A new study aims to finally settle the questions and fears surrounding the only cox-2 inhibitor still on the market, Celebrex (celecoxib). The Clevland Clinic's Cardiovascular Coordinating Center will conduct a trial comparing Celebrex with two NSAIDs -- ibuprofen and naproxen -- among arthritis patients with heart disease.

    Experts are hailing the comparison as an important step in understanding the risks and benefits of common arthritis medications.

    "I think it's a good idea. I'm glad there is going to be a systematic and organized look at the safety and efficacy of these," said Gary Firestein, professor and chief of rheumatology, allergy, and immunology at University of California San Diego. "Right now people are mostly just guessing."

    The Cleveland Clinic will recruit approximately 20,000 participants over 18 months. These patients will participate in the trial for at least two years, until 715 heart events are observed, explained Steven Nissen, lead investigator and medical director of the Cardiac Coordinating Center. He added that the study could be stopped prematurely if a safety monitoring board decides one or more of the drugs are too risky to continue.

    The trial will include primarily patients with heart disease, along with a few who have high risk factors. This is the only way to really get significant data on any heart risks associated with these treatments, explained Nissen, who is also the president-elect of the American College of Cardiology.

    "You can't learn anything if you can't study the population that's actually at risk," he said.

    Glenn Birnbaum, an emergency room physician and medical marketing consultant, said the results of the study would influence prescribing behavior, if they answer the most pressing questions about these products. In addition to comparing efficacy, rate of cardiac side effects, and mortality rates, Birnbaum wants a comparison of the rates of gastrointestinal bleeding.

    Steven Chen, assistant professor at the University of Southern California's School of Pharmacy, is also interested in comparing the safety of these products on the stomach.

    "Celebrex has never been shown to be any safer on the stomach than traditional NSAIDs," he said via e-mail.

    Although Pfizer will provide funding, the study will be governed by an independent board of academics. The members will not be able to accept consulting fees, Nissen said.

    "Maximum transparency is essential," he said. "Public confidence has been really shaken, particularly for clinical trials for this class of drugs."

    Nissen agreed that the trial poses a risk for Pfizer, because no one really knows what the results will indicate and it will cost at least $100 million.

"It's really courageous," he said. "I'm delighted to see that Pfizer is really willing to answer these questions."

    But Chen believes that Pfizer can only gain from the results of this trial. Celebrex has suffered because of the fear associated with COX-2 inhibitor drugs, although it is less specific to the COX-2 enzyme than Bextra or Vioxx are.

    "If Celebrex ends up causing more heart attacks then they might as well forget about making any more money on it, which is where it's headed anyway," he said via e-mail. "If they're able to show that Celebrex is as safe as the other traditional NSAIDs, then Celebrex will make a big comeback."

Articles

Doctors and academics are praising Pfizer’s plan to allow the Cleveland Clinic to compare Celebrex with two NSAIDs. Is the company courageous, or is it taking to big of a risk?

Study Will Compare Heart Risk of COX-2 and NSAIDs

An unexplained rise in the false-positive rate of OraSure Technologies' breakthrough rapid oral test for HIV has led several major clinics to discontinue using the test. Most recently, the LA Gay and Lesbian Center stopped using the OraQuick Advance oral test Dec. 16, after an unusual number of people received inaccurate results.

    According to center spokesman Jim Key, the organization has noted 13 false positive tests since they began tracking these occurrences in November. They don't know exactly how many oral tests they administered during this period, but Key estimated around 600.

    Clinics that provide HIV testing typically expect false positives in the range of four per thousand tests administered. All patients with a positive oral test are given follow-up blood tests. This fall, however, clinics in New York, San Francisco and Los Angeles have noted higher-than-expected rates of false positives.

    Between September and November, the San Francisco County Health Department recorded six to eight false positives out of every 1000 tests.

    The LA Gay and Lesbian Center has not changed the way it administers the OraQuick tests, Key said. It began using the oral rapid test before its June 2004 FDA approval, during the product's clinical trials. Prior to this fall, they have always been confident in the OraQuick Advance oral test. The center continues to use the OraQuick fingerstick test, which uses blood rather than oral fluid, Key noted.

    OraSure Technologies met with the Gay and Lesbian Center earlier this week and with San Francisco County in October. Dowling said the company provided her department with cameras to take pictures of problematic test results. OraSure is also contacting other customers to address questions or problems with the product, according to spokeswoman Jennifer Moritz.

    "The company is moving forward in a scientific and systematic manner, in collaboration with affected customers, healthcare officials, and government agencies, in order to determine the reasons for these unexpected results as rapidly as possible," she said via e-mail.

    Similar to a pregnancy test, the OraQuick Advance test shows one line if the individual is negative and two lines if he is positive. The problematic test results tend to show one strong line and a second, very faint, line, Dowling said. Since there is more than one line, it is counted as positive but results for tests with this faint second line are often reversed in the follow-up stage, she added.

    Dowling speculated that the faint line could show up when someone is seroconverting, an early stage of infection when HIV antibodies are first present. The oral test is more sensitive to HIV antibodies than the blood test, so the antibodies might not be detected in the follow-up. As a result, a second blood test should be administered two weeks after getting results from the first one, she said.

    But no one is certain about the cause of this recent increase in false positives. Neither the Gay and Lesbian Center nor OraSure are speculating publicly about what may cause this increase in false positive test results.

    "The jury is still out," Dowling said. "We still have to figure it out."

    The county is working with state officials on a protocol for tests with a faint second line. This would involve following up with the OraQuick fingerstick test. A blood test would still be required even if the second test was negative, but it could help offer people with these types of confusing results peace of mind while they wait two weeks for the results of the blood test.

    Both Key and Dowling emphasized the importance of reliable results that people can get right away. Rapid results have increased the number of people getting tested, according to Key, and he is very concerned that if they are perceived as unreliablethe testing rates might decrease.

    "We want to make it as easy as possible for people to get an HIV test," Dowling said.

    Dowling noted that San Francisco County has not seem a decrease in the number of people being tested since the increase in false positives was made public, but these reports have not been out for very long. Key added that his organization wants to make it clear that they still have confidence in the OraSure fingerstick test and that rapid testing is still available at the clinic.

A recent spate of false positive results using OraSure’s test has officials and company representatives scrambling to figure out what is causing these anomalies and how to stop them from impacting testing rates.

Los Angeles Facility Discontinues Use of OraQuick Rapid HIV Test

Medication for acid reflux disease is equally effective as surgery, according to the first in a series of reports on improving healthcare quality that were mandated by the 2003 Medicare Modernization Act.

    An extensive analysis of previously reported data conducted by the Agency for Healthcare Research and Quality (AHRQ) found that the older histamine type-2 blockers are not as effective as the newer protein pump inhibitors (PPIs) that appeared in the 1990s, explained Kenneth Fink, director of the agency's evidence-based practice centers program.

    According to Fink, there were some differences between traditional surgery, where part of  the stomach is wrapped around the sphincter separating the esophagus from the stomach, cutting off the flow of acid, and PPIs. But the clinical importance of these differences is unclear, he continued.

    The management of symptoms and increase in quality of life is similar between surgery and PPIs, he said, as are the long-term treatment benefits. Neither type of therapy was better at preventing cancer either.

    The information in the AHRQ report does not contain any new information, according to Jon Spechler, professor of gastroenterology at the University of Texas Southwestern Medical Center. The PPIs offer very good treatment, and surgery is not necessary for most people, he said.

    What's more, the effects of the surgery do not seem to last, after 10 years up to two-thirds of surgery patients are back on the medication, Spechler said. 

    But some experts have speculated that PPIs might have long-term side effects that would not appear until patients have used them for many more years, Spechler added. 

    For example, preventing acid from being pumped into the stomach up regulates the hormone that normally detects low levels of stomach acid, gastrin. As a result, people on PPIs have high levels of gastrin. Some people think this could cause growth problems, such as cancer, down the road.

    There was not enough evidence about new, non-invasive endoscopic surgery techniques to compare them to either drugs or traditional surgery, Fink said.

Spechler said the endoscopic techniques were too new and that he would not recommend them yet.

Agency hopes to inform healthcare providers and patients about comparisons of treatments for gastroesophagealreflux disease.

Pharmaceutical Executive-12-21-2005

Study Will Compare Heart Risk of COX-2 and NSAIDs

Los Angeles Facility Discontinues Use of OraQuick Rapid HIV Test

Analysis Confirms Medication is as Effective as Surgery for Acid Reflux