By Cathy O’Neil, a data scientist who lives in New York City and writes at
mathbabe.org
Yesterday I caught a lecture at Columbia given by statistics professor
David Madigan, who explained to us the story of
Vioxx and
Merck. It’s fascinating and I was lucky to get permission to retell it here.
Disclosure
Madigan has been a paid consultant to work on litigation against Merck. He doesn’t consider Merck to be an evil company by any means, and says it does lots of good by producing medicines for people. According to him, the following Vioxx story is “a line of work where they went astray”.
Yet Madigan’s own data strongly suggests that Merck was well aware of the fatalities resulting from Vioxx, a blockbuster drug that earned them $2.4b in 2003, the year before it “voluntarily” pulled it from the market in September 2004. What you will read below shows that the company set up standard data protection and analysis plans which they later either revoked or didn’t follow through with, they gave the FDA misleading statistics to trick them into thinking the drug was safe, and set up a biased filter on an Alzheimer’s patient study to make the results look better. They hoodwinked the FDA and the New England Journal of Medicine and took advantage of the public trust which ultimately caused the deaths of thousands of people.
The data for this talk came from published papers, internal Merck documents that he saw through the litigation process, FDA documents, and SAS files with primary data coming from Merck’s clinical trials. So not all of the numbers I will state below can be corroborated, unfortunately, due to the fact that this data is not all publicly available. This is particularly outrageous considering the repercussions that this data represents to the public.
Background
The process for getting a drug approved is lengthy, requires three phases of clinical trials before getting FDA approval, and often takes well over a decade. Before the FDA approved Vioxx, less than 20,000 people tried the drug, versus 20,000,000 people after it was approved. Therefore it’s natural that rare side effects are harder to see beforehand. Also, it should be kept in mind that for the sake of clinical trials, they choose only people who are healthy outside of the one disease which is under treatment by the drug, and moreover they only take that one drug, in carefully monitored doses. Compare this to after the drug is on the market, where people could be unhealthy in various ways and could be taking other drugs or too much of this drug.
Vioxx was supposed to be a new “
NSAID” drug without the bad side effects. NSAID drugs are pain killers like
Aleve and
ibuprofen and
aspirin, but those had the unfortunate side effects of gastro-intestinal problems (but those are only among a subset of long term users, such as people who take painkillers daily to treat chronic pain, such as people with advanced arthritis . The goal was to find a pain-killer without the GI side effects. The underlying scientific goal was to find a
COX-2 inhibitor without the
COX-1 inhibition, since scientists had realized in 1991 that COX-2 suppression corresponded to pain relief whereas COX-1 suppression corresponded to GI problems.
Vioxx Introduced and Withdrawn From the Market
The timeline for Vioxx’s introduction to the market was accelerated: they started work in 1991 and got approval in 1999. They pulled Vioxx from the market in 2004 in the “best interest of the patient”. It turned out that it caused heart attacks and strokes. The stock price of Merck plummeted and $30 billion of its market cap was lost. There was also an avalanche of lawsuits, one of the largest resulting in a $5 billion settlement which was essentially a victory for Merck, considering they made a profit of $10 billion on the drug while it was being sold.
The story Merck will tell you is that they “voluntarily withdrew” the drug on September 30, 2004. In a placebo-controlled study of colon polyps in 2004, it was revealed that over a time period of 1200 days, 4% of the Vioxx users suffered a “cardiac, vascular, or thoracic event” (CVT event , which basically means something like a heart attack or stroke, whereas only 2% of the placebo group suffered such an event. In a group of about 2400 people, this was statistically significant, and Merck had no choice but to pull their drug from the market.
It should be noted that, on the one hand Merck should be applauded for checking for CVT events on a colon polyps study, but on the other hand that in 1997, at the International Consensus Meeting on COX-2 Inhibition, a group of leading scientists issued a warning in their Executive Summary that it was “… important to monitor cardiac side effects with selective COX-2 inhibitors”. Moreover, in an internal Merck email as early as 1996, it was stated there was a “… substantial chance that CVT will be observed.” In other words, Merck knew to look out for such things. Importantly, however, there was no subsequent insert in the medicine’s packaging that warned of possible CVT side-effects.
What the CEO of Merck Said
What did Merck say to the world at that point in 2004? You can look for yourself at
the four and half hour Congressional hearing (seen on C-SPAN which took place on November 18, 2004. Starting at 3:27:10, the then-CEO of Merck,
Raymond Gilmartin, testifies that Merck “puts patients first” and “acted quickly” when there was reason to believe that Vioxx was causing CVT events. Gilmartin also went on the Charlie Rose show and repeated these claims, even go so far as stating that the 2004 study was
the first time
they had a study which showed evidence of such side effects.
How quickly
did
they really act though? Were there warning signs before September 30, 2004?
Arthritis Studies
Let’s go back to the time in 1999 when Vioxx was FDA approved. In spite of the fact that it was approved for a rather narrow use, mainly for arthritis sufferers who needed chronic pain management and were having GI problems on other meds (keeping in mind that Vioxx was way more expensive than ibuprofen or aspirin, so why would you use it unless you needed to , Merck nevertheless launched an
ad campaign with Dorothy Hamill and spent $160m (compare that with Budweiser which spent $146m or Pepsi which spent $125m in the same time period .
As I mentioned, Vioxx was approved faster than usual. At the time of its approval, the completed clinical studies had only been 6- or 12-week studies; no longer term studies had been completed. However, there was one underway at the time of approval, namely a study which compared Aleve with Vioxx for people suffering from
osteoarthritis and
rheumatoid arthritis.
What did the arthritis studies show? These results, which were available in late 2003, showed that the CVT events were more than twice as likely with Vioxx as with Aleve (CVT event rates of 32/1304 = 0.0245 with Vioxx, 6/692 = 0.0086 with Aleve, with a p-value of 0.01 . As we see this is a direct refutation of the fact that CEO Gilmartin stated that they didn’t have evidence until 2004 and acted quickly when they did.
In fact they had evidence even before this, if they bothered to put it together (in fact they stated a plan to do such statistical analyses but it’s not clear if they did them- or in any case there’s so far no evidence that they actually did these promised analyses .
In a previous study (“Table 13? , available in February of 2002, the could have seen that, comparing Vioxx to placebo, we saw a CVT event rate of 27/1087 = 0.0248 with Vioxx versus 5/633 = 0.0079 with placebo, with a p-value of 0.01. So, three times as likely.
In fact, there was an even earlier study (“1999 plan” , results of which were available in July of 2000, where the Vioxx CVT event rate was 10/427 = 0.0234 versus a placebo event rate of 1/252 = 0.0040, with a p-value of 0.05 (so more than 5 times as likely . This p-value can be taken to be the definition of statistically significant. So actually they knew to be very worried as early as 2000, but maybe they… forgot to do the analysis?
The FDA and Pooled Data
Where was the FDA in all of this?
They showed the FDA some of these numbers. But they did something really tricky. Namely, they kept the “osteoarthritis study” results separate from the “rheumatoid arthritis study” results. Each alone were not quite statistically significant, but together were amply statistically significant. Moreover, they introduced a third category of study, namely the “Alzheimer’s study” results, which looked pretty insignificant (more on that below though . When you pooled all three of these study types together, the overall significance was just barely not there.
It should be mentioned that there was no apparent reason to separate the different arthritic studies, and there is evidence that they did pool such study data in other places as a standard method. That they didn’t pool those studies for the sake of their FDA report is incredibly suspicious. That the FDA didn’t pick up on this is probably due to the fact that they are overworked lawyers, and too trusting on top of that. That’s unfortunately not the only mistake the FDA made (more below .
Alzheimer’s Study
So the Alzheimer’s study kind of “saved the day” here. But let’s look into this more. First, note that the average age of the 3,000 patients in the Alzheimer’s study was 75, it was a 48-month study, and that the total number of deaths for those on Vioxx was 41 versus 24 on placebo. So actually on the face of it it sounds pretty bad for Vioxx.
There were a few contributing reasons why the numbers got so mild by the time the study’s result was pooled with the two arthritis studies. First, when really old people die, there isn’t always an autopsy. Second, although there was supposed to be a
DSMB as part of the study, and one was part of the original proposal submitted to the FDA, this was dropped surreptitiously in a later FDA update. This meant there was no third party keeping an eye on the data, which is
not
standard operating procedure for a massive drug study and was a major mistake, possibly the biggest one, by the FDA.
Third, and perhaps most importantly, Merck researchers created an added “filter” to the reported CVT events, which meant they needed the doctors who reported the CVT event to send their info to the Merck-paid people (“investigators” , who looked over the documents to decide whether it was a bonafide CVT event or not. The default was to assume it wasn’t, even though standard operating procedure would have the default assuming that there was such an event. In all, this filter removed about half the initially reported CVT events, and about twice as often the Vioxx patients had their CVT event status revoked as for the placebo patients. Note that the “investigator” in charge of checking the documents from the reporting doctors is paid $10,000 per patient. So presumably they wanted to continue to work for Merck in the future.
The effect of this “filter” was that, instead of it seeming 1.5 times as likely to have a CVT event if you were taking Voixx, it seemed like it was only 1.03 as likely, with a high p-score.
If you remove the ridiculous filter from the Alzheimer’s study, then you see that as of November 2000 there was statistically significant evidence that Vioxx caused CVT events in Alzheimer patients.
By the way, one extra note. Many of the 41 deaths in the Vioxx group were dismissed as “bizarre” and therefore unrelated to Vioxx. Namely, car accidents, falling of ladders, accidentally eating bromide pills. But at this point there’s evidence that Vioxx actually accelerates Alzheimer’s disease itself, which could explain those so-called bizarre deaths. This is not to say that Merck knew that, but rather that one should not immediately dismiss the concept of statistically significant just because it doesn’t make intuitive sense.
VIGOR and the New England Journal of Medicine
One last chapter in this sad story. There was a large-scale study, called the VIGOR study, with 8,000 patients. It was published in the
New England Journal of Medicine on November 23, 2000. See also this
NPR timeline for details. They didn’t show the graphs which would have emphasized this point, but they admitted, in a deceptively round-about way, that Vioxx has 4 times the number of CVT events than Aleve. They hinted that this is either because Aleve is protective against CVT events or that Vioxx is bad for it, but left it open.
But Bayer, which owns Aleve, issued a press release saying something like, “if Aleve is protective for CVT events then it’s news to us.” Bayer, it should be noted, has every reason to want people to think that Aleve is protective against CVT events. This problem, and the dubious reasoning explaining it away, was completely missed by the peer review system; if it had been spotted, Vioxx would have been forced off the market then and there. Instead, Merck purchased 900,000 preprints of this article from the NE Journal of Medicine, which is more than the number of practicing doctors in the U.S.. In other words, the Journal was used as a PR vehicle for Merck.
The paper emphasized that Aleve has twice the rate of ulcers and bleeding, at 4%, whereas Vioxx had a rate of only 2% among chronic users. When you compare that to the elevated rate of heart attack and death (0.4% to 1.2% of Vioxx over Aleve, though, the reduced ulcer rate doesn’t seem all that impressive.
A bit more color on this paper. It was written internally by Merck, after which non-Merck authors were found. One of them is Loren Laine. Loren helped Merck develop a sound-byte interview which was 30 seconds long and was sent to the news media and run like a press interview, even though it actually happened in Merck’s New Jersey office (with a backdrop to look like a library with a Merck employee posing as a neutral interviewer. Some smart lawyer got the outtakes of this video made available as part of the litigation against Merck. Check out this
youtube video, where Laine and the fake interviewer scheme about spin and Laine admits they were being “cagey” about the renal failure issues that were poorly addressed in the article.
The Damage Done
Also on the
Congress testimony I mentioned above is Dr. David Graham, who speaks passionately from minute 41:11 to minute 53:37 about Vioxx and how it is a symptom of a broken regulatory system. Please take 10 minutes to listen if you can.
He claims a conservative estimate is that 100,000 people have had heart attacks as a result of using Vioxx, leading to between 30,000 and 40,000 deaths (again conservatively estimated . He points out that this 100,000 is 5% of Iowa, and in terms people may understand better, this is like 4 aircraft falling out of the sky every week for 5 years.
According to
this blog, the noticeable downwards blip in overall death count nationwide in 2004 is probably due to the fact that Vioxx was taken off the market that year.
Conclusion
Let’s face it, nobody comes out looking good in this story. The peer review system failed, the FDA failed, Merck scientists failed, and the CEO of Merck lied to Congress and to the people who had lost their husbands and wives to this damaging drug. The truth is, we’ve come to expect this kind of behavior from traders and bankers, but here we’re talking about issues of death and quality of life on a massive scale, and we have people playing games with statistics, with academic journals, and with the regulators.
Just as the financial system has to be changed to serve the needs of the people before the needs of the bankers, the drug trial system has to be changed to lower the incentives for cheating (and massive death tolls just for a quick buck. As I mentioned before, it’s still not clear that they would have made less money, even including the penalties, if they had come clean in 2000. They made a bet that the fines they’d need to eventually pay would be smaller than the profits they’d make in the meantime. That sounds familiar to anyone who has been following the fallout from the credit crisis.
One thing that should be changed immediately: the clinical trials for drugs should not be run or reported on by the drug companies themselves. There has to be a third party which is in charge of testing the drugs and has the power to take the drugs off the market immediately if adverse effects (like CVT events are found. Hopefully they will be given more power than risk firms are currently given in finance (which is none - in other words, it needs to be more than reporting, it needs to be an active regulatory power, with smart people who understand statistics and do their own state-of-the-art analyses – although as we’ve seen above even just Stats 101 would sometimes do the trick.
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.
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A spine surgeon who was spearheading the development of a new artificial disc decided to use it to help a colleague with back pain. When he inserted the device, the patient's original pain went away but now he had pain in a new area. The patient sued, and the judge in the case ruled the surgeon had failed to follow his own recommendations for inserting the disc. The patient was awarded $650,000 plus legal costs.
Virginia spine surgeon Hallett H. Mathews, MD, was principal investigator for the Maverick, Medtronic's artificial disc that was going through the FDA clearance process at the time. Highly regarded by colleagues, Dr. Mathews had served on the board of directors of the North American Spine Society. When Connecticut spine surgeon Eric M. Garver, MD, told him he was suffering from chronic pain in his back and left leg, Dr. Mathews agreed to personally insert the Maverick disc in him.
The new device made the pain go away, but afterwards Dr. Garver started experiencing pain in a new area on the other side of his body. Patrick Mastroianni, MD, a Connecticut neurosurgeon who operated on Dr. Garver 2 weeks after the original surgery, said he retrieved a bone fragment the size of an olive that was lodged next to the disc and appeared to be pressing against the nerve root in his spine.
Removing the fragment alleviated some of Dr. Garver's pain, but the pain still could not be controlled, even by taking multiple drugs every day. Dr. Garver blamed Dr. Mathews and sued him in state court. Dr. Mathews would not settle the case, insisting he had been careful when inserting the artificial disc and had not violated the standard of care. Furthermore, he disagreed that he had left the bone fragment behind and also questioned whether it was causing the pain.
The judge disagreed with Dr. Mathews's version of the facts and ruled that he had violated his own standard of care. The standard for inserting the Maverick, formulated in part by the defendant himself, required that the disc space be "meticulously cleared of materials that might be driven into nerves behind the disc space by insertion of the artificial disc," the judge wrote.
Thomas Albro, an attorney for Dr. Garver, said Dr. Mathews had helped his client, but only to a point. "He had been suffering significant pain and Dr. Mathews successfully relieved it," the attorney said. "The problem was there was new pain after surgery." Michael Goodman, an attorney for Dr. Mathews, declined to comment.
After years of planning, the Maverick never reached the U.S. market. Before it could complete the FDA clearance process, Medtronic's competitor, Synthes, won a patent infringement lawsuit against Medtronic over the Maverick. Medtronic, which had been selling the Maverick around the world, withdrew it from all markets.
Transvaginal mesh, a surgical mesh often used to treat conditions such as pelvic organ prolapse is now being linked to a number of harmful side effects. Women who have been implanted with surgical mesh say they have experienced complications such as mesh erosion, mesh contraction, infection, inflammation, blood loss, and pelvic pain to name a few.
The implant, which is manufactured by pharmaceutical giant Johnson & Johnson, is generally used to repair weakened or damaged tissue. There are various types of pelvic mesh products on the market such as Gynemesh, Prolene Mesh, Prolift, Prolift-M, and TVT.
Thousands of women have filed complaints against Johnson & Johnson claiming that the company marketed surgical mesh as being a safe, effective, and reliable medical device implanted through safe, effective, and minimally invasive techniques for the treatment of pelvic organ prolapse. It is alleged that Johnson & Johnson made exaggerated and misleading expectations about the safety and utility of the product though it has been shown to have high failure, injury, and complication rates.
Since surgical mesh has been shown to fail at properly performing as intended, severe and permanent injuries requiring frequent and often unbearable re-operations are necessary.
It is believed that Johnson & Johnson underrepresented and withheld information about the tendency of the products to fail and cause injuries and complications. Furthermore, the
adverse effects of surgical mesh show that Johnson & Johnson failed to properly test and research to evaluate the risks and benefits of surgical mesh prior to marketing it to patients and health care providers.
Pelvic organ prolapse occurs when the internal structures that support the uterus and bowel become so weak or stretched that the organs drop from their normal position and bulge or prolapse into the vagina. While not a life threatening condition, women with pelvic organ prolapse often experience pelvic discomfort, disruption of their sexual, urinary, and defecatory functions, and an overall reduction in their quality of life.
The Food and Drug Administration recommends that health care providers realize that pelvic organ prolapse can be treated successfully without
mesh, thus escaping possible injuries and complications.
Emirates SkyCargo, the freight division of Emirates, one of the fastest growing international airlines, is expanding its North American operation, increasing trade opportunities between U.S. businesses and its global network.
After the launch of daily passenger service from Dallas/Fort Worth (DFW and Seattle-Tacoma (SEA International airports from 2nd February and 1st March respectively, Emirates SkyCargo will connect seven points in North America with trade prospects in more than 100 destinations worldwide.
"Our daily, non-stop flights from DFW and SEA will offer the fastest routes to the Middle East and beyond," said Ram Menen, Emirates' Senior Divisional Vice President Cargo. "We look forward to helping more American firms enhance their trade ties not only with the UAE, but also with markets in parts of South Asia, such as China, South Korea and Japan, and numerous points throughout Emirates' extensive network in India and Africa."
Air cargo being transported on Emirates' flights departing the U.S will be handled at the airline's Cargo Mega Terminal, housed at its state-of-the-art hub at Dubai International Airport (DXB , a location within eight hours of two-thirds of the world's population.
"When combined with the efficiency of one of the youngest fleets in the skies, unrivalled ground-handling facilities, and the very latest information technology at our Cargo Mega Terminal, Emirates SkyCargo is the ideal partner for Dallas/Fort Worth and Seattle-based businesses as they look to boost trade," added Menen.
The airline's expansion will help facilitate the growth of trade in the Seattle metropolitan area that produced US$ 24.2 billion in total exports and US$2.7 billion in United Arab Emirates exports in 2008 and 2009 respectively. Texas exports to the UAE also expect significant growth, having reached over $1.7 billion in 2009 - an increase of more than 192 per cent since 2002.*
International cargo being exported from Dallas/Fort Worth will include oilfield equipment, electronic parts, computers, cell phones, medical equipment and pharmaceuticals; heading for markets across the Emirates network, from the UAE to Australia, India and Uganda. Leading import commodities such as communications equipment, automotive components, apparel and fabrics will come from a range of markets including Taiwan, Japan, Sri Lanka and Saudi Arabia.
Exports on the Seattle route are expected to include fresh fruits and vegetables, electrical equipment and machinery, as well as medical equipment and aircraft parts, which will be transported to the UAE and surrounding destinations in the Middle East. China and South Korea will also be key trading partners, with leading imported commodities set to consist of electronic equipment, footwear and apparel.
Emirates' DFW and SEA services join existing operations from New York (JFK , Houston (IAH , Los Angeles (LAX and San Francisco (SFO , as well as Toronto (YYZ in Canada, further strengthening trade ties between North America, the UAE and points throughout Emirates' network of 121 destinations, which will be bolstered in coming months with a further three routes - Seattle (1st March , Ho Chi Minh City (4th June , Barcelona (3rd July and Lisbon (9th July .
- Ends -
Notes to Editors:
*Source: Brookings Institution Study
About Emirates SkyCargo:
Emirates SkyCargo is the
freight division of Emirates. Reflecting Emirates' overall policy of excellence in every area of operation, Emirates SkyCargo's investment in highly-qualified staff, the very latest information technology, the most efficient aircraft and the finest ground handling facilities - including its
priority cargo service - has made it a significant force in the global air cargo industry.
In the 2010-11 financial year, Emirates SkyCargo carried 1.8 million tonnes of cargo across its network, contributing 17.4 per cent of the airline's total transport revenue. Based out of Dubai International Airport, its Cargo Mega Terminal is designed to handle 1.2 million tonnes of cargo a year.
Anti-seizure drug delivery via an autoinjector device represents a quick and safe status epilepticus treatment method, a major new study has found.
Crucially, the technique also produces a more effective response compared to traditional intravenous anticonvulsive administration.
Autoinjectors are spring-loaded syringes filled with a single drug dose and, generally, their contents are injected straight into the thigh muscle. They're in widespread use within the US armed forces and are already used to rapidly treat a number of conditions including multiple sclerosis, arthritis and anaphylaxis.
Now - although further research is still needed - status epilepticus is set to be added to this list, off the back of the successful trial results produced from the study - named RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial .
Autoinjected Drugs Study
Funding for the RAMPART autoinjected drugs study was provided by NINDS (the US National Institute of Neurological Disorders and Strokes and, on 16 February, it was published by the New England Journal of Medicine.
Status epilepticus claims 55,000 lives in the US alone every 12 months but the standard IV drug supply technique used to counter its effects can be too time-consuming. The RAMPART study's goal was to establish whether the use of autoinjectors could make a difference and two different anticonvulsants were used, including midazolam - a benzodiazepine class drug marketed as Versed, Hypnovel and Dormicum - and lorazepam, another benzodiazepine with the trade names Temesta and Ativan.
The researchers involved compared two emergency drug supply scenarios - midazolam delivered via an autoinjector and lorazepam delivered intravenously - and the benchmark used was the state of the patients involved once they'd arrived at hospital.
Effective Seizure Treatment
The researchers found that, on average, the seizures had stopped in 73 per cent of those that were given autoinjected midazolam by the time they reached hospital. With a 10 per cent higher recovery rate compared those injected with lorazepam, this made the autoinjected midazolam the more effective seizure treatment.
Therefore, according to the deputy director of NINDS, Doctor Walter Koroshetz: "This study establishes that rapid intramuscular injection of an anticonvulsant drug is safe and effective."
Almost 900 patients were involved in the RAMPART study, along with 79 hospitals located in 17 US cities. The autoinjectors, meanwhile, were made available by the US Department of Defense's CBMS (Chemical Biological Medical Systems division.
Autoinjector image copyright ‘Kilinkie' - Courtesy Wikimedia Commons
See also:
AMERICA'S Food and Drug Administration (FDA
announced late on February 14th that 19 medical practices had bought counterfeit Avastin, a popular cancer drug. The doctors and hospitals bought the bum drug from a foreign supplier, Quality Specialty Products.
As such scares go, this one could have been worse. Avastin, marketed in America by
Genentech, is an injected drug available only in hospitals and doctors’ offices. Presumably health professionals will spot rogue bottles more quickly than the average consumer would have. So far there have been no reports of dangerous reactions, unlike some past incidents—in 2008 a sham bloodthinner made in China killed several Americans and sickened many more.
But the news is alarming nonetheless. It is another reminder of how vulnerable the drug supply-chain remains. About 80% of ingredients for drugs bought in America are made elsewhere. Imports of drugs have grown by nearly 13% a year. Regulators have
done their best to keep up. The FDA has opened a series of offices abroad; inspections of foreign factories increased by 27% from 2007 to 2009. It is trying to foster
collaboration with foreign regulators—apparently Britain’s Medicines and Healthcare Products Regulatory Agency alerted the FDA to the counterfeit Avastin. More changes are on the way. Generic drug companies have agreed to pay the FDA a fee to increase foreign inspections, a deal that must still be approved by Congress. The FDA is also
asking the government for more money to expand its operations in China. But change, as the recent fiasco proves, is not coming fast enough.
Read more on http://www.babaramdevmedicines.com/divya-products/divya-arshkalp-vati.htm »
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