By Steven DiJoseph
The New York Post is reporting that Ortho-McNeil has already Ã¢â‚¬Å“settled a dozen lawsuits for millions of dollars in the last few monthsÃ¢â‚¬Â for claims arising out of the use of the companyÃ¢â‚¬â„¢s Ortho Evra contraceptive patch.
Currently, there are over 100 additional cases pending across the U.S. that Ortho-McNeil appears to be interested in resolving and this has prompted attorneys to submit their clientÃ¢â‚¬â„¢s claims for settlement.
The Post article indicates that the twelve settlements include claims by women between 18 and 47. One settlement is believed to be in excess of $10 million.
The Ortho Evra cases vary from most claims where a prescription drug is the subject of personal injury or wrongful death litigation. Typically, the Ã¢â‚¬Å“victimÃ¢â‚¬Â was already suffering from a physical or psychological illness, disease, or other health problem that may have actually caused, or at least contributed to, the alleged injuries.
For example, in the thousands of cases pending against Merck & Co. for injuries or deaths allegedly caused by the COX-2 inhibitor arthritis drug, Vioxx, virtually all of the plaintiffs had pre-existing medical problems like diabetes, hypertension, elevated cholesterol, and various degrees and types of cardiovascular disease.
In the case of antidepressants claimed to have been responsible for suicides, many of the alleged victims were already suffering from significant psychological or psychiatric problems.
Thus, it is often difficult to definitively link a drug directly to an injury or death because of these intervening factors that may, or may not, have played some role in the process.
This, however, is not the situation with respect to deaths and injuries allegedly caused by the Ortho Evra birth control patch since the victims are virtually all healthy women of child-bearing age with no significant medical problems that would otherwise explain their sudden and tragic deaths.
In fact, many of the victims have been between the ages of 14 and 30 and in excellent health.
This is precisely what is alleged by the family of a 20-year-old woman who died from a pulmonary thromboembolism (blood clot) after using the Ortho Evra contraceptive patch for 10 months.
In June 2004, paramedics arrived to find the decedent in an idioventricular rhythm. She had reportedly collapsed after awakening and gasping for air.
The paramedics performed advanced cardiac life support and rushed the young woman to the hospital by ambulance where efforts to resuscitate her failed.
An autopsy revealed the immediate cause of death was pulmonary thromboembolism.
A lawsuit in that case was filed by the law firm of Parker & Waichman, LLP, in the United States District Court for the District of New Jersey in Newark, New Jersey.
In February of this year, the FDA acknowledged the finding of a new study that indicates women using the Ortho Evra birth-control patch have an elevated risk of developing blood clots.
As previously reported, notwithstanding the fact that this is far from the first evidence linking this potentially fatal side-effect to the Ã¢â‚¬Å“patch,Ã¢â‚¬Â the FDA has taken the position that the results are only preliminary and do not require immediate action other than to advise women to discuss this risk with their doctors.
According to Dr. Daniel Shames, who is director of the division of reproductive and urological drug products at the FDA, preliminary findings from a study by i3 Drug Safety found women using the patch had twice the risk of developing blood clots compared to women taking birth-control pills.
In November 2005, after years of debate over the safety of the Ortho Evra birth-control patch, the drugÃ¢â‚¬â„¢s manufacturer Ortho-McNeil (a subsidiary of Johnson & Johnson Ã¢â‚¬â€œ the worldÃ¢â‚¬â„¢s 4th largest drugmaker) finally acknowledged the fact that women who use the product are at a significantly greater risk of blood clots, stroke, and death than woman who use other forms of oral contraceptives.
Ortho-McNeil has now admitted that women who use the patch can be exposed to up to 60% more estrogen than they would be exposed to if they were taking a birth control pill instead.
Critics of both the Ã¢â‚¬ËœpatchÃ¢â‚¬â„¢ and the FDAÃ¢â‚¬â„¢s approval and monitoring practices, however, see the warning as simply another example of economics being placed above public safety.
There has been a constant chorus of warnings about the extremely serious side-effects associated with the patch from a number of experts as well as the consumer watchdog group, Public Citizen (www.worstpills.org) and the Associated Press.
Several other lawsuits have already been commenced around the U.S. alleging that serious injuries and deaths have been caused by the Patch.
CBS News also presented a significant story from Austin, Texas, concerning documents produced in the course of a pending lawsuit involving a young mother who was paralyzed by a stroke only 12 days after she began using the patch. She is now a total invalid.
According to that story, Ortho-McNeilÃ¢â‚¬â„¢s own records show the company received some 500 reports of serious health problems associated with the patch between April 2002 and December 2004. During that time only 61 such reports were received with respect to all types of existing oral contraceptives.
In addition, there were four times as many strokes in women using the patch as in women using oral contraceptives even though three times as many women were taking those other forms of birth control.
Finally, the evidence indicated, that in medically confirmed cases, the risk of blood clots is 14 times as high with the patch.
An investigative report published by the Associated Press on July 18, 2005 linked the birth control patch, which contains a combination of norelgestromin and ethinyl estradiol, to an increased risk of blood clots and deaths (compared to older contraceptives) in some young healthy women.
Ortho Evra, like the other hormonal contraceptives, has a black box warning about an increased risk of cardiovascular adverse reactions in older women who smoke. This type of warning is the strongest that the FDA can request.
The Associated Press follow-up story is even more damning, however. In that article, the AP stated:
Ã¢â‚¬Å“Documents released to attorneys as a result of that litigation show Ortho McNeil has been analyzing the FDA’s death and injury reports, creating its own charts that document a higher rate of blood clots and deaths in association with the patch than with the pill.
In addition, an internal Ortho McNeil memo shows that the company refused, in 2003, to fund a study comparing its Ortho Evra patch to its Ortho-Cyclen pill because of concerns there was Ã¢â‚¬Ëœtoo high a chance that study may not produce a positive result for EvraÃ¢â‚¬â„¢ and there was a Ã¢â‚¬Ëœrisk that Ortho Evra may be the same or worse than Ortho-Cyclen.Ã¢â‚¬â„¢Ã¢â‚¬Â
The patch, like many oral contraceptives, contains two hormones, a progestin and an estrogen. The progestin in Ortho Evra is a new drug (2001) known as norelgestromin, and the estrogen is an existing one known as ethinyl estradiol.
Ortho Evra was approved by the Food and Drug Administration (FDA) in November 2001 and is the first contraceptive product to be approved as a skin patch. It was launched and marketed in a series of Ã¢â‚¬Å“glitzyÃ¢â‚¬Â television ads featuring Ã¢â‚¬Å“sexy models.Ã¢â‚¬Â (CBS 11/2/05).
In 2004, the drug accounted for more than 9.9 million prescriptions with sales topping $411 million.
Contraceptives are often referred to as second- or third-generation based on their progestin component. Since some experts classify norelgestromin as a third-generation progestin, Ortho Evra is considered third-generation contraceptive.
Public citizen first listed some third-generation oral contraceptives as Ã¢â‚¬Å“DO NOT USEÃ¢â‚¬Â drugs in 1998 and 1999 because of an increased risk of blood clots compared to the older, second-generation birth control pills. Thus, elevated blood levels of progestin as well as estrogen are possible with the Patch.
The Associated Press used the Freedom of Information Act (FOIA) to obtain adverse drug reaction reports for Ortho Evra from the FDA and reportedly found that of the 23 cases in which death was the outcome, doctors reviewing the cases found 17 that appeared to be blood-clot-related, including 12 from 2004.
Since the FDA estimates that it receives reports of only between 1% and 10% of the serious adverse drug reactions that actually occur, the death rate for Ortho Evra may be significantly higher.
The Associated Press also analyzed the reviews of clinical trial results done by FDA physicians and scientists prior to the drugÃ¢â‚¬â„¢s approval. Those results were submitted for review by Ortho-McNeil in support of Ortho-Evra and are available on the FDAÃ¢â‚¬â„¢s Web site at: http://www.fda.gov/cder/foi/nda/2001/021-180_ORTHO.htm.
Significantly, Ortho-McNeil and the FDA medical officer reviewing Ortho Evra strongly disagreed about whether two cases of blood clots in the lungs (pulmonary embolus) in young women participating in the pre-approval clinical trials were caused by the drug. The FDA medical officer wrote:
Ã¢â‚¬Å“THE REVIEWER DOES NOT AGREE WITH THE SPONSORÃ¢â‚¬â„¢S [Ortho-McNeil] ABOVE CONCLUSIONS. The two cases of pulmonary embolus, a serious and potentially fatal condition, must be counted as two cases in the … groupÃ¢â‚¬Â [emphasis in the original].
The FDA medical officer also included the following statement in his comments:
The professional product labeling and information written specifically for women using Ortho-Evra Ã¢â‚¬Å“should reflect the possible increased risk of venous thromboembolism (VTE) [blood clots] associated with this new transdermal combination hormonal contraceptive containing the new molecular entity progestin norelgestromin (17d-norgestimate).Ã¢â‚¬Â
In addition, the medical officer expressed concern that 211 out of 3,088 women (6.8%) in the pre-approval clinical trials gained 10 or more pounds in the trials and noted that the contraceptive effectiveness of Ortho-Evra was reduced in women weighing more than 198 pounds (90 kilograms).
The professional product label warns that Ortho-Evra should not be used in the following circumstances:
A history of heart attack or stroke
Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), or eyes
A history of blood clots in the deep veins of your legs
Chest pain (angina pectoris)
Known or suspected breast cancer or cancer of the lining of the uterus, cervix or vagina
Unexplained vaginal bleeding (until your doctor reaches a diagnosis)
Hepatitis or yellowing of the whites of your eyes or of the skin (jaundice) during pregnancy or during previous use of hormonal contraceptives such as ORTHO EVRA, NORPLANT [levonorgestrel], or the birth control pill
Liver tumor (benign or cancerous)
Known or suspected pregnancy
Severe high blood pressure
Diabetes with complications of the kidneys, eyes, nerves, or blood vessels
Headaches with neurological symptoms
Use of oral contraceptives (birth control pills)
Disease of heart valves with complications
Need for a prolonged period of bed rest following major surgery
An allergic reaction to any of the components of Ortho Evra
Women who may be using Ortho Evra should contact their physician if any of the following warning signals develop:
Sharp chest pain, coughing of blood, or sudden shortness of breath (indicating a possible clot in the lung)
Pain in the calf (indicating a possible clot in the leg)
Crushing chest pain or tightness in the chest (indicating a possible heart attack)
Sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness, or numbness in an arm or leg (indicating a possible stroke)
Sudden partial or complete loss of vision (indicating a possible clot in the eye)
Breast lumps (indicating possible breast cancer or fibrocystic disease of the breast; ask your doctor or health care professional to show you how to examine your breasts)
Severe pain or tenderness in the stomach area (indicating a possibly ruptured liver tumor)
Severe problems with sleeping, weakness, lack of energy, fatigue, or change in mood (possibly indicating severe depression)
Jaundice or a yellowing of the skin or eyeballs accompanied frequently by fever, fatigue, loss of appetite, dark colored urine, or light colored bowel movements (indicating possible liver problems)
Since contraceptives are usually prescribed to young, healthy women they should be associated with the lowest possible risk of serious adverse drug reactions.
Blood clots in the lungs were seen in two women given Ortho Evra in clinical trials conducted before the drug was even approved (in addition to several similar cases after the drug was marketed).
There is also no evidence that the patch is a superior contraceptive compared to older second-generation birth control pills. As stated in the September 2005 issue of Worst Pills Best Pills (published by Public Citizen); Ã¢â‚¬Å“Rarely do randomized pre-approval studies, the scientific Ã¢â‚¬Ëœgold standardÃ¢â‚¬â„¢ for proving safety or efficacy, present such strong evidence of a serious problem.Ã¢â‚¬Â
As a result of what it considers strong evidence of the increased risk of blood clots and death, Public Citizen states: Ã¢â‚¬Å“There is no medical reason for women to use the more dangerous Ortho Evra rather than one of the older, better understood, and equally effective oral contraceptives.Ã¢â‚¬Â
When reading the November 2005 Ortho-McNeilÃ¢â‚¬â„¢s Press Release, the first thing that becomes obvious is that the company made a concerted effort to present the information in a way that was difficult (if not impossible) for anyone but an expert to understand.
For example, the acronym AUC is used without definition thereby making the references to estrogen concentrations difficult to extrapolate. AUC, however, is a measure of how much of a drug reaches the bloodstream in a set period of time, usually 24 hours.
AUC is calculated by plotting drug blood concentration at various times during a 24-hour or longer period and then measuring the area under the curve between 0 and 24 hours.
When the implications of AUC are considered with respect to the amount of estrogen that can be released in a given period of time, the result is shocking since that amount can easily exceed 50 mg which is well beyond the level already determined to be unsafe.
There is also the belief held by some experts that the combination of the amount of estrogen and the type of progestin used in the Ortho Evra patch is at the heat of the blood clot problem.
A previous study conducted with respect to another contraceptive product (the Ã¢â‚¬Å“vaginal ringÃ¢â‚¬Â) documented these excessively high levels of estrogen associated with the patch almost a year ago in the journal Contraception.
In addition to the risks already discussed cigarette smoking increases the risk of serious cardiovascular side effects from hormonal contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. As a result, women who use hormonal contraceptives, including Ortho Evra, should not smoke.
Finally, litigation involving Ortho Evra has been gaining momentum in recent months and especially in light of the Associated Press investigation. The litigation focuses on the claim that Ortho-McNeil knew of the blood clot risk and even disagreed with the FDA medical officer who suspected the two incidents that occurred during the clinical trial were related to the drug.
A lawsuit was filed in July 2005 against Ortho-McNeil on behalf of a 30-year-old woman who suffered fatal blood clots thought to be linked to the Ortho Evra risk. The woman was admitted into the intensive care unit shortly before her death suffering from severe headache, visual problems, vomiting, and nausea.
The other deaths reported in connection with Ortho Evra risk factors were the result of heart attacks and strokes. One of the most recent deaths linked to Ortho Evra was suffered by a 25-year- old woman who suffered fatal headaches thought to be linked to a surge of hormone release from the birth control patch.
The youngest woman to die (as reported to that point) was an 18-year-old college student who collapsed in the New York subway. As of February ten other women ranging in age from 18 to 27 had also sued Ortho-McNeil.
In September 2005, Parker & Waichman announced it had filed suit against Ortho-McNeil on behalf of a 37-year-old woman who suffered a pulmonary embolism after using the Ortho Evra contraceptive patch for seven months. That suit was also filed U.S. District Court for the District of New Jersey.
According to the complaint in that lawsuit, from April 2002 through September 2003, the U.S. Food and Drug Administration logged 9,116 reports of adverse events because of the patch.
This is significant since there were only 1,237 adverse reports by women taking the leading oral contraceptive, Ortho Tri-Cyclen, over a six-year period even though that drug was used by almost six times as many women as Ortho Evra in 2003.
Ortho-McNeil has routinely denied the allegations that these deaths and injuries were the result of Ortho Evra risk factors. It claimed that the Ã¢â‚¬Å“unsolicited reportsÃ¢â‚¬Â it received were not reliable evidence of a problem with the drug.
The company also claimed its own investigation had not found any causal factor linking these deaths to Ortho Evra and relied on the absence of any reports of fatal adverse side-effects during the clinical trials as proof of the drugÃ¢â‚¬â„¢s safety.
Ortho-McNeilÃ¢â‚¬â„¢s reluctance to accept even the possibility that the patch could be at fault has lead to the drug being kept on the market without adequate warnings. Even the companyÃ¢â‚¬â„¢s press release and FDA advisory regarding new labeling requirements do not satisfy the patchÃ¢â‚¬â„¢s many critics.
In the eyes of those critics, the fact that Ortho-McNeil notified the FDA that it has undertaken a Ã¢â‚¬Å“much larger studyÃ¢â‚¬Â with respect to the potential problem of blood clots, strokes, and death associated with the patch merely prolongs the time in which millions of women are exposed to an unacceptable risk of catastrophic injuries and death.
In addition to the rather cryptic press release issued by Ortho-McNeil in November 2005 concerning the serious risks associated with its Ortho Evra birth control patch, the FDA published its own information for consumers wishing to learn more about those potentially fatal side-effects (http://www.fda.gov/bbs/topics/news/2005/NEW01262.html)http://www.fda.gov/cder/drug/infopage/orthoevra/qa.htm) as well as a series of questions and answers. (
Ã¢â‚¬Å“FDA is announcing a revision to the label for the drug Ortho EvraÃ¢â‚¬Â¦This change includes a new bolded warning about higher exposure to estrogenÃ¢â‚¬Â¦Higher levels of estrogen may put some women at increased risk for getting blood clots.Ã¢â‚¬Â
Ã¢â‚¬Å“A woman on Ortho Evra may be exposed to approximately 60% more estrogen than if she were taking a typical 35 microgram estrogen birth control pillÃ¢â‚¬Â¦Estrogen use is linked to blood clots in the legs and lungs and other clotting problems such as strokes and heart attacks.Ã¢â‚¬Â
Ã¢â‚¬Å“In general, a woman may be at higher risk for getting side effects if she takes higher doses of estrogenÃ¢â‚¬Â¦Women should discuss with their health care professional whether the Ortho Evra patch is a good method of contraception for them.Ã¢â‚¬Â
Following the November 2005 Ortho-McNeil Press Release and FDA Advisory, there have been several reports of doctors and other healthcare providers curtailing or even suspending the prescribing of the patch.
The Wall Street Journal (WSJ) reported that: Ã¢â‚¬Å“Many doctors have stopped writing prescriptions for a popular form of birth control after the Food and Drug Administration warned earlier this month of increased hormone exposure to women who use it.Ã¢â‚¬Â (http://online.wsj.com/article/0,,SB113262165542103693,00.html?mod=djemHL).
According to the WSJ: Ã¢â‚¬Å“[A] number of individual practitioners and major health-care providers say they don’t want to take any chances. In Memphis, Tenn., obstetrician and gynecologist Henry Sullivant says he has stopped writing new patch prescriptions and suggests that his roughly two dozen patch users try other forms of prescription contraceptives, such as the pill or a monthly vaginal ring. Pennsylvania State University, which provides health services for 42,000 students, is no longer issuing prescriptions and says it is considering whether to contact all students who have been given prescriptions for Ortho Evra, even if they are no longer at the university.Ã¢â‚¬Â
In a effort to exercise caution, similar actions are being taken by many other university health officials including those at the University of Texas at Austin, Stanford University, the University of California, Berkeley, and Connecticut College in New London, Connecticut where one patch user experienced a blood clot in her lung last spring.
In addition Ã¢â‚¬Å“Lee Shulman, incoming board chairman of the Association of Reproductive Health Professionals, says he expects that Ã¢â‚¬Ëœthere will be a decrease in useÃ¢â‚¬â„¢ of Ortho Evra, at least over the next several months. He adds that he has been inundated with doctor and patient phone calls asking whether the patch is safe to use.Ã¢â‚¬Â
A number of litigation attorneys we spoke with, who are familiar with pharmaceutical litigation, agreed that it is becoming more difficult for doctors and major healthcare providers like colleges and universities to ignore the mounting evidence and warnings and simply write thousands of prescriptions for the patch. The percentages indicate that when that many prescriptions are written some of the women will suffer serious or fatal adverse reactions.
There are also many well-publicized law suits alleging deaths and catastrophic injuries from the very side-effects contained in the November 2005 warning. Thus, any doctor writing a prescription for the patch from that point on is doing so at his or her peril. Given the potentially fatal side-effects of the drug, writing a prescription now could be considered irresponsible in terms of good and accepted medical practice especially if an otherwise healthy woman is paralyzed or dies from a stroke caused by blood clots after using the patch.
Thus, it is not surprising that so many healthcare providers are rethinking their policies and recommending alternative medications to their patients.
In mid-November another high-profile wrongful death case was commenced against Ortho-McNeil and Johnson & Johnson. It involves Alycia Brown, an eighth-grader in La Crosse, Wisconsin, who died of blood clots in her lower pelvis on May 7, 2004. She had been using the Ortho Evra birth control patch for about eight weeks.
The federal law suit filed in Madison by her parents claims the patch was the cause of their daughterÃ¢â‚¬â„¢s tragic death. The La Crosse County medical examiner has found that Ortho Evra was a likely contributing factor in AlyciaÃ¢â‚¬â„¢s death.
Although many lawsuits have already been commenced against Ortho-McNeil and its parent company, Johnson & Johnson, for injuries and deaths allegedly caused by the patch, the 14-year-old is now the youngest known victim.
As Lorie Brown, AlyciaÃ¢â‚¬â„¢s grieving mother, told reporters: “I’m out to let people know: get off (Ortho Evra). That’s my biggest goal here. I didn’t save her life, but maybe I can save somebody else’s.” It seems that many responsible doctors and major healthcare providers are trying to do the very thing.
Many experts, consumer watchdog groups, and critics of the FDA drug approval process in general, and Ortho Evra in particular, believe the dangers presented by the patch should have been obvious to the FDA before the drugs approval. They are also concerned by the FDAÃ¢â‚¬â„¢s position that it intends to do nothing at present because it considers the information regarding the risks posed by Ortho Evra merely Ã¢â‚¬Å“preliminary.Ã¢â‚¬Â
It appears that Ortho-McNeilÃ¢â‚¬â„¢s discreet efforts to settle as many of the outstanding claims as it can is a tacit recognition that the cases are valid and must be resolved in order to avoid massive litigation costs, substantial damage awards (including the possibility of punitive damages), and appeals.
A respected appellate attorney we spoke with, who is familiar with pharmaceutical litigation, stated that: Ã¢â‚¬Å“No major drug company would authorize such significant settlements and the apparent pursuit of others if there was no basis for the claims.Ã¢â‚¬Â
He also added that: Ã¢â‚¬Å“Since the Ortho Evra claims involve young, healthy women, it appears the injuries and deaths will simply continue as long as the drug remains on the marketÃ¢â‚¬Â
(Sources: New York Post (4.9.06), HoustonChronicle.com, Public Citizen Ã¢â‚¬â€œ Worst Pills Best Pills; CBS News; Associated Press; Food and Drug Administration (FDA) Web Site; Wall Street Journal; Newsinferno.com Archives)