Citizens Petition before the Food and Drug Administration requesting withdrawal for sale of Norplant

The undersigned submits this petition under the Federal Food, Drug and Cosmetic Act to request the Commissioner for Food and Drugs to withdraw Norplant's approval for sale in the United States.

Action requested

We request the Commissioner of the Food and Drug Administration to withdraw the approval for sale of Norplant , a contraceptive system which was initially approved for sale on 10 December 1990 and which is manufactured by Wyeth-Ayerst.

Statement of grounds

1. Background of Norplant

Norplant consists of six small flexible capsules made of Silastic tubing and filled with a synthetic progesterone, levonorgestrel. The capsules are surgically placed subdermally on the inner side of a woman's upper arm where they are supposed to remain for five years and then be removed surgically. Norplant is manufactured by Wyeth-Ayerst, a division of American Home Products. Population Council holds the patent for Norplant.

Norplant has been widely used in contraceptive programs around the world. It is claimed that extensive clinical trials, involving some 55,000 women from 46 countries, have proven both the safety and the efficacy of Norplant.1

2. Reasons for market withdrawal

There are three principle reasons the Commissioner of the Food and Drug Administration should withdraw Norplant's approval for sale in the United States:

American women have been experiencing adverse health conditions after beginning to use Norplant that are more serious and sustained than the side effects cited by Norplant's manufacturer at the time of approval.

These possibly Norplant -related conditions have not occurred only in the United States but are part of a larger and continuing pattern of adverse health conditio ns for users worldwide which stretches from relatively wealthy and medically astute American woman to desperately poor women in nations like Bangladesh, Haiti, and Brazil. These adverse health conditions pose a serious and as yet unquantified health risk to American women because, as we document below, data reflecting the reality of Norplant's hazards to women were simply not collected following its introduction into several countries. It is unclear whether, and to what extent, these facts were made known to the Commissioner of the Food and Drug Administration prior to the Norplant's approval in 1990.

The drug delivery system known as Norplant, which introduces a constant, low-level of progesterone into a woman's body, may diminish their natural resistance to HIV and other sexually transmitted diseases.

3. Detail of reasons for withdrawal

A.

Adverse health conditions among American women subsequent to Norplant use American women have experienced serious adverse health conditions after having Norplant inserted, including, but not limited to, increased intracranial fluid pressure (pseudo tumor cerebri), chronic blurred vision, leading to permanent vision loss or blindness, and tumors in the brain and other organs.2,3 Other conditions experienced by American women include hyper menorrhea (heavy and sustained menstrual bleeding), serious acne, sustained nausea, debilitating headaches, weakness or paralysis in one or more limbs, endometriosis, ovarian cysts, weight gains of sometimes over 100 pounds, severe mood swings and irritability. Further, many have found that having Norplant removed was a much more difficult procedure than they had been originally advised.4

Representative Case histories:

Patsy Smith of Houston, Texas: As documented by the BBC, three months after having Norplant inserted into her upper arm, Ms. Smith began to experience increasing degrees of vision impairment compounded by severe headaches. Concerned, she consulted Dr. Rosa Tang, a noted neuro-ophthalmologist. Dr. Tang diagnosed Patsy as suffering from pseudo tumor cerebri, which is a condition of increased intracranial fluid pressure. This increased pressure had crushed Ms. Smith's optic nerves, leading to functional blindness in one eye and serious vision loss in theother.

Noting that Ms. Smith's condition had arisen subsequent to her recent Norplant insertion, Dr. Tang decided to investigate the possibility of a causal relationship. She wrote to all the other ophthalmologists in Texas to ask if any of their patients on Norplant had developed similar symptoms. Over 100 cases were brought to her attention, including 40 women with some degree of vision impairment and eight with conditions similar to her patient's. Dr. Tang described for the BBC the impact thenumbers had on her concerns about Norplant:

"[The survey result] was very surprising for me because I had not seen any reports in the literature at this time of such a link between Norplant and pseudo tumor cerebri and I was surprised of the fact that there were so many patients that seemed to be having the condition related to Norplant. I think that there is enough out there that there is a possibility of a link between the two [and] that a larger-scale study should be done if Norplant is to be continued."5

Wanda Candelaria of Chicago, Illinois: Ms. Candelaria had Norplant inserted in a Chicago hospital in February 1992. She bled on 572 of the following 630 days, until she refused to further believe her doctor's reassurances that her body would eventually "adjust" to Norplant, and insisted that it be removed from her arm.
During the removal procedure the sensory nerves in her arm were damaged and she has lost all sensation in an area extending from the insertion site down to her elbow. She will likely require additional reparative surgery.6

Lyne Triezenberg of Elwood, Illinois: Following the Norplant insertion Ms. Triezenberg experienced vision loss so severe it requires the use of bifocal glasses even though she is only 24 years of age.7

Kim Colglazier of Elkert, Indiana: Four days after the insertion of Norplant in August of 1992, Ms. Colglazier began to experience blurred vision and within one week had permanently lost all sight in her right eye. A Cleveland doctor she consulted about her condition diagnosed her as having had a stroke resulting from the use "birth control." At the time the only method of birth control Ms. Colglazier used was Norplant. 8

Patient A: Four weeks after having Norplant inserted in 1994, a 40 year old woman approached doctors complaining of blurred vision in her left eye. She reported never having previously used hormonal contraceptives. Her vision continued to deteriorate over several months and was increasingly impaired in color and light sensitivity. Magnetic resonance imaging indicated a homogenous mass crowding the left optic nerve opening. The tumor mass was surgically removed and was later found to be a meningothelial neoplasm which tested positive for progesterone receptors. This and other incidents suggest that hormones may stimulate meningiomas to grow.9

FDA "Medwatch" Data:

Writing recently in the medical journal Obstetrics and Gynocolgy, Diane K. Wysowki, PhD, and Lahn Green, Rph, MPH, report that between February 1991 and December 1993 the FDA received 5800 reports of adverse health events involving Norplant use through its Medwatch Reporting System. These events included pseudo tumor cerebri (39 cases), hospitalizations because of infections and difficulties with removal (24 cases), strokes (15 cases), and thrombocytopenia (6 cases - 1 death), among others.10

Wysowki and Green, who are employees of the FDA's Division of Epidemiology and Surveillance, maintain that it is difficult to track incidents of adverse reactions to Norplant through the Medwatch system because reporting is voluntary and depends therefore on a number of uncontrollable factors.

Even so, they concluded that while "[n]one of the reporting rates exceeded the expected rates of the disease . . . reporting rates for stroke and pseudo tumor cerebri (which reflect the under reporting of an unknown magnitude) were close enough to the expected rates (which reflect all causes) to suggest that Norplant users may be at an increased risk of developing these disorders."11

This public expression of concern by FDA employees over the possibility of adverse health conditions resulting from Norplant is remarkable. Given the limitations of the data reviewed by Wysowki and Green, it is likely that the incidence of pseudo tumor cerebri and other adverse conditions are far higher than reported. The cases of Patsy Smith and Patient A reported above, for example, were not available to these FDA researchers at the time their article was written.

Evidence from Norplant's manufacturer, Wyeth-Ayerst:

There is evidence that Wyeth-Ayerst, Norplant's manufacturer, is aware of the link between their product and most, if not all, of the adverse conditions mentioned above. This is strongly suggested by the fact that on 24 July 1994 Wyeth-Ayerst promulgated a new set of guidelines for doctors and clinics involved in the insertion of Norplant. These guidelines list 23 new adverse medical conditions in connection with Norplant, including pseudo tumor cerebri, stroke, and arm pain and numbness. Not only were these adverse health conditions not mentioned to most if not all of the women offered Norplant insertion prior to 24 July 1994, it is alleged that they have still not been offered to the hundreds of thousands of women currently experiencing Norplant and further alleged that physicians or clinics have not been required to inform perspective Norplant users of the new information.12

Another indication that the manufacturer is concerned about the adverse medical conditions associated with Norplant comes in the form of a report that Wyeth-Ayerst has "quietly undertaken a major medical inquiry into [Norplant's ] long term health effects."10 This report, which appeared in the Cleveland Plain Dealer on 17 September 1995, cites "internal documents" at Wyeth-Ayerst which expressed concern over a "lack of information" about the health consequences of Norplant, and in particular about its effect on young women ages 13-20.

The newspaper further reported that Wyeth-Ayerst in 1992 hired Trudy Bush, a researcher at the University of Maryland School of Medicine, to design a study to test the effect of Norplant on young women. Ms. Bush is quoted in the story as saying that "The data the company had [at the time of FDA approval] was for women in their 20's and 30's, whereas Norplant was being used by adolescent women a lot. We just don't know what giving a 15-year-old five years of progesterone will do."

The Cleveland Plain Dealer also quotes Lisa Rarick, whom it identifies as the FDA official who recommended approving Norplant in 1990, as having urged Wyeth-Ayerst to do more studies which included "adverse events" on American women since "the original trials mainly involved women older than 18 in some of the poorest countries."

Rarick also recalled being concerned over "differences in reporting of side effects" between women in the developing world and those in the United States. Based on information which we have collected and document in the next section, we believe those concerns are amply justified.

B. Adverse conditions in United States linked to adverse conditions in developing world

The adverse medical conditions experienced by American women are part of a worldwide pattern. Women in Bangladesh, Haiti and Brazil have all reported problems with Norplant similar to those suffered by American women, most often while taking part in allegedly "clinical" trials for this drug delivery system. There is evidence which suggests that the organizations responsible for administering Norplant "trials" in the developing world (and collecting data from those "trials") did not inform women as to Norplant's experimental nature, ignored women's problems with the contraceptive and failed to remove the capsules even when asked repeatedly to do so. Disturbingly, these results of the "trials" were later represented as "successful" and as an indication of how well women around the world had accepted Norplant.

B 1. Norplant in Bangladesh.

The first attempt to market Norplant to Bangladeshi women came in 1981. Advertisements were placed in Bengali-language newspapers entitled: "A new birth control method /NORPLANT/ a wonderful innovation of modern science." The advertisement went on to say that Norplant was for women, can be implanted under the skin of the arm, will "ensure sterility" for five years and that its effects are reversible when removed. Nothing in the advertisement mentioned anything about the product's experimental nature, possible adverse health conditions associated with the product, or other concerns.

Alerted to Norplant's experimental nature, women's groups in Bangladesh protested its use.13 Over 150 concerned doctors, pharmacists and health workers petitioned the Minister for Health to stop the trial, which was subsequently "postponed."14

In 1985 Norplant returned to Bangladesh again, this time in the context of an explicit "clinical trial," "to assess the acceptability and effectiveness of this new method among Bangladeshi women" and"to decide about the use of Norplant on a large scale in the family planning programme." Nothing was said in 1985 about the "trial" doing anything to measure safety or adverse conditions from Norplant use.15

The 1985 "trial" was conducted in secret, without the public announcements and advertising campaigns that had alerted Bangladeshi women groups four years prior. The details of the "trial," particularly the negative impact it had on the very poor women who were recruited to take part, would remain unknown today had it not been for the efforts of a handful of social workers. Faced with almost a total lack of cooperation and candor from the organizations conducting the "trial" in Bangladesh, they went themselves into slum areas and villages and located women who had been inserted with the "five year needle," as it was called in Bengali.

These social workers were able to obtain an informational handout which was given to women who were considering Norplant. The handout represented that Norplant is a 100 percent effective contraceptive for five years; that it is "relatively easier" than other methods; that its side-effects are "less than that of the pill;" that the user can take out the Norplant whenever she wants; that after taking out Norplant fertility returns in one year; that it is possible to carry out normal movements and work when it is in the body; and that there is no need to use any other method with Norplant. 16

The FDA regulation governing the evaluation of foreign clinical studies states that such studies will be accepted provided "they are well designed, well conducted, performed by qualified investigators, and conducted in accordance with ethical principles acceptable to the world community." The regulation then cites verbatim the Helsinki Declaration on Biomedical Research. The workers who discovered the trial were aware of the acceptable international norms for such research and carefully interviewed women who had been given Norplant about their experience. The following are some of the discrepancies between what the international norms declare should have occurred and what actually happened in Bangladesh.

International norms

Practice among women contacted

Acceptors of the method under investigation should be informed that it is on trial and that they are subjects of biomedical research. vs. None of the women interviewed knew that Norplant was still on trial. The only information given to them was that "it is one of the contraceptive methods and lasts for five years."

Research subjects must be throughly informed about known and possible side-effects. vs. Only a few of the women interviewed were told that there would be some "disturbance" in their menstrual cycles, but these were told "there would be no more problem."

After providing all information pertinent to the research project, consent from theresearch subjects must be obtained. vs. The social workers could not find information which showed any sign of seeking informed consent from the women who are about to have the Norplant capsules inserted.

A medical examination and screening of the research subjects should be conducted before they enter the trial. vs. Only cursory medical exams, weight and blood pressure checks, were offered to most women.

Medical support should be given to researchsubjects once they enter the trial. vs. Medical support ranged from vitamins to pain killers to "unidentified prescriptions on plain white paper" to nothing at all.

Source: Ubinig "Norplant, the five year needle: an investigation of the Norplant trial in Bangladesh from the user's perspective," Issues in Reproductive and Genetic Engineering, 1990 3(3):223-224.

B 2. Bangladeshi women in their own words

Despite assurances that the side effects of Norplant would be "less than the pill," a significant number of Bangladeshi women began to experience severe adverse effects subsequent to insertion. In interviews with BBC, here is how some of them described their condition:17

"Suddenly [after having Norplant inserted] my body became weak, quite suddenly. I couldn't get up, couldn't take care of my children, couldn't cook. I was bedridden"

"[m]y limbs felt like collapsing, as if they were being wrenched apart. I couldn't work or eat even. I had to lie in bed for 3 months. I couldn't do anything ... I was bleeding all the time."

"In 6 months [I went to the clinic] about 12 times. Yes, about 12 times. I went to the clinic and pleaded I'm having so many problems. I'm confined to bed most of the time. Please remove it [Norplant ]' My health broke down completely. I was reduced to skin and bone. I had milk and eggs when I could, but that did me no good."

"I felt so bad, my body felt so weak, even my husband told me it was all very inconvenient ... [My husband] says he'll get another wife tomorrow. I told the doctors, Please take it out, I'm having so many problems ... I felt like throwing myself under the wheels of a car."

"I couldn't see. I couldn't look at things at a distance. I had trouble focusing. You know in the village we light oil lamps. I couldn't look at them. They looked like the sun, as red and large as the sun. If I looked into the distance, my eyes would water ... If I went out of doors, my eyes became absolutely dark. I couldn't see anything at all as if my eyes had become affected by blindness."

B 3. Difficulties with removal

The difficulty that Bangladesh women experienced in having Norplant despite earlier assurances that "users can remove Norplant whenever they want," is worthy of separate comment. Many women found that they were expected to carry Norplant to term no matter what adverse medical conditions they developed. In interviews with the BBC, here is how some of the women and representatives of women's groups described their situation:18

"I went to the clinic as often as twice a week. But [the clinic workers] said, This thing we put in you costs 5000 takas. We'll not remove it unless you pay this money.' Of course I feel very angry. I went to several other doctors and offered them money to take those things out, but they all refused. I went to three or four of them and they said that these can only be taken out by those who put them in. They said that, if they tried they might go to jail." [italics added].

Farida Ahktar, a Bangladeshi woman's rights activist, recounts that: "One woman when she begged to remove it, said I'm dying, please help me get it out'. They said OK, when you die you inform us, we'll get it out of your dead body', so this is the way they were treated. In a slum area people are living in a very small [area], like 5ft by 7ft where at least five family members are living and these woman are working outside. The most important resource they have is their own healthy condition."

"We have ... information where these women have told us that they have sold their cow or the goat which was the only asset they had for treatment because she had to get well, otherwise the family can't survive, so in order to save her, they had to, you know, sell the cow or if they didn't want to treat her then she suffered, so the family was suffering either way. In every sense these people were totally torn. Their economic condition were torn, their family happiness was totally gone."

When the Norplant trial ended in 1993, the organizations involved announced that "Norplant is a highly effective, safe and acceptable method among Bangladeshi women." They claimed that less than 3% reported significant medical problems.19 The report did not mention women being denied removal of the implants or the problems with adverse conditions. Dr. Nasreen Huq, a physician and consultant to the government of Bangladesh on women's health issues, subsequently criticized the trial:

"I think the Norplant trials were bad science, really shoddy science, because they were not recording the side-effects. They were scolding women when they wanted to report side-effects, they were scolding women if they came in at a time when they were not scheduled to come in for a follow-up check. Their request for removal were disregarded, were not even recorded during the trial. So how can they tell us that it was an acceptable method for women and that this has been scientifically tested out, you know? When continuation rates reflect caution, reflect refusal to remove, reflect disregard of women's concerns, reflect disregard for women's health, how can they even accept that this has been the work of scientists?

"When you conduct a trial in this sort of setting, you are simply taking advantage of them being poor. You've access, cheap access, to subjects, and you can write it up as a successful trial. You're not in any way advancing science, you're taking advantage of a situation in which women are poor and they don't want to have more children, and by providing this method, or conducting this trial, you are not in any way letting them out of their desperate situation. I mean, I have been trained in science and I'm sorry, this is not science."20

C. Norplant in Haiti

A Norplant trial in Haiti is also alleged to have been conducted in a less than ethical manner. Medical Anthropologist Catherine Maternowska, who was sent to Haiti on a Population Council fellowship, witnessed serious abuses in the trial:21

"Side effects in the context of Haitian women's lives are horrible. With the Norplant users they were extremely sever. Bleeding could go on for 18 months ... Another bad side-effect was headaches ... many women collapsed from this method under sheer exhaustion. They could not work so ill, theywere unable to function. Ms. Maternowska also reported that Haitian women had difficulty having the implant removed:

"One woman came in with an infection in her arm. She was a market woman, she carried heavy loads on her head and when she came in asking to get the insert out, the doctor complained and he complained and he looked at me and he was used to having me in the clinic and he said, Oh Cathy, look at this woman, she's an animal, she wants her Norplant out, she's an animal. She has to be in the study and she wants it out now. What's her problem?'

"They proceeded to throw her li terally onto the table, lie her down so that they could ... take the N orplant insertion out. They threw her head to the [side like] this and they gave her the anaesthesia but before the anaesthesia had actually taken effect in her skin they started pulling the inserts out and making incisions and pulling the inserts out. Because [of] the infection in her arm it looked painful, it was red, it was swollen, and the muscle and sinew tissue had grown over the implants, they were pulling and she was wailing, she was crying why, why,' and they continued calling her an animal. "I think it's a sham, it's disgusting, it appalled me that this kind of research was going on. When someone's looking for help, looking for a solution to their poverty and what they find is something that just makes their poverty worse, it's a huge, huge sadness."

C 1. Norplant in Brazil

Lack of informed consent was also a problem in the Brazilian Norplant trial where, in contravention of international standards governing informed consent, only minimal information was offered about possible adverse medical conditions:

"The scarce in formation as to possible harm caused by Norplant is clear in paragraphs 4 and 5 [of the term of responsibility form]: I understand that the Norplant implants are in general well tolerated but it is probable that I [will experience] significant alterations in my menstrual cycle, which include irregularity, intermenstrual bleeding or even periods of no menstruation at all. It is possible that other side effects may also occur, such as headaches, weight gain, acne and other symptoms related to the use of hormones."22

At the same time, an attempt seems to have been made to have the patients take full responsibility for any adverse medical conditions which they did experience:

"...[i]nstead of signing a document legally declaring knowledge of risk, internationally known as informed consent, the women were given a term of responsibility' in the attempt to pass onto them the onus of possible harm caused by Norplant. "23

Adverse conditions which appeared after Norplant insertion were severe and often ignored

"According to the study done by Koifman and colleagues, the women in Rio de Janeiro showed dramatic' changes in weight. One woman gained 38 kg in 9 months ... Another had immediate weight gain of 2 kg in the first week, 3 kg in the second and also developed depression and respiratory problems."24

" Menstrual irregularities' are treated in the same way. Behind the term increased bleeding' are hidden blood losses that would be considered pathological if the classic gynecol ogical terms and concepts, such as menorrhea and hypermenorrhea were used. Interviews with Norplant users ... indicate that many women had continuous bleeding lasting more than 20 or even 30 days. The impacts of these irregularities' on these women's day-to-day lives are ignored."25

D. Progesterones similar to levonorgestrel may be linked to increased risk for HIV

On 6 May 1996 the National Institutes of Health announced the results of a study conducted at the Aaron Diamond AIDS Research Center. In the study researchers placed progesterone pellets under the skins of 18 rhesus monkeys and placebos under the skins of 10 others. Large doses of simian immune deficiency virus (SIV) were then injected into the vaginas of all the monkeys. Of the 18 monkeys with progesterone implants, 14 were infected with SIV. Of the ten monkeys with the placebo, only one was.26

This study suggests that progesterone and similar hormones, when left at a consistently high level for a long enough period of time, may so thin vaginal walls that they reduce the vagina's ability to act as a barrier to HIV and other sexually transmitted diseases. The hormone delivery system which exposes vaginal tissue to significant levels of hormones for the longest period of time is Norplant.

Contraceptive manufacturers and agencies of both Federal and local government have urged women using hormone-based contraception to also use barrier methods, such as condoms, for additional protection. However, given that one recent study found the condom failure rates around the world ranged as high as 13.3%27 it seems wise to consider withdrawing from use a drug delivery system which may place women at great risk of contracting HIV.

4. Conclusions

Significant numbers of American women have experienced adverse medical conditions after having Norplant inserted. Some women have become permanently disabled, notably those who have suffered serious vision loss, suffered extensive scarring, or have partially lost the use of the arm in which Norplant was inserted. A drug delivery device which, in even a small percentage of cases, cause permanent disability which is not correctable by its removal must be viewed with considerable scepticism.

These adverse medical conditions have been experienced by women abroad as well, sometimes, as we have documented, in the context of Norplant trials which were conducted under unethical, dishonest and inappropriate conditions. These trials make it clear that a significant number of women experienced side effects which went beyond those cited in the Norplant literature, including hyper menorrhea, debilitating headaches, bodily weakness, vision problems, and other troubling conditions. The under reporting of adverse medical conditions from these trials is particularly troubling, as it suggest that the trial sponsors were more concerned about Norplant's speedy introduction or approval than the health and safety of current or future users.

There are other troubling aspects to Norplant's history. It has been reported that FDA officials, subsequent to approving Norplant, urged the manufacturer to further investigate its long-term effects. Given that Norplant is little more than a long-term drug delivery system, this advice strikes the outside observer as somewhat odd. Surely all questions about the medical wisdom of prescribing a multi-year drug regimen should have been answered prior to approval. Furthermore, two years after Norplant's approval, the manufacturer updated its own product guidelines to include a greatly expanded list of adverse medical conditions.

Add to these concerns the recent simian study linking progesterone to the thinning of vaginal walls with the consequential increased risk of infection with HIV.

In our opinion, based on the information presented above, we believe that Norplant is a flawed drug delivery system which has:

• An unacceptably high risk/benefit ratio, especially as compared to other progesterone- related drug delivery systems
• The potential for causing serious disability
• An unacceptably wide range of post-usage adverse health conditions
• An unknown long-term health risk
• A possible link with increased HIV risk

We respectfully request the U.S. Food and Drug Administration to disapprove Norplant for sale in the United States.

Environmental impact

We claim categorical exclusion under 21 CFR Sec. 25.24.

Contrary information

On the American section the biggest element of contrary information is the lack of information. FDA officials cited in the article in Obstetrics and Gynecology, as well as in the Cleveland Plain Dealer indicate that the question of cause and effect with Norplant and these adverse health conditions is still, officially, up in the air.

On the question of the foreign trials there are some studies which contradict some of the studies presented here. Although even these do not contradict all of the information. Akhter et. al declare that a study including follow ups with Bangladeshi women at 1, 3 and 6 months indicated that roughly 59% of Bangladeshi women in the study discontinued using Norplant before the study ended. Of those, 75% requested removal for menstrual problems. 45.3% of those cited heavy bleeding as the reason for their withdrawal. The study cites only a small number 2.2% of other side effects.28

Some of the concerns about the trials in Brazil were addressed by Anibal Faundes of the Population Council in Brazil. Faundes states that there need to be a differentiation between a "pre-introductory" study and a "clinical trial." Because Norplant had already been approved in Finland and clinical trials conducted in other places "there was no need," Fuandes says, for Brazilian women to have more extensive medical examinations before starting Norplant. Further, the terms or responsibility form outlined the major side-effects from Norplant and should be considered enough for informed consent.29

Irving Sivan, Senior Scientist for The Population Council's Center for Biomedical Research took issue with some of the numbers offered by the two FDA staff members in Obstetrics and Gynecology.30 Sivans states that they have underestimated the total of woman-years of Norplant use in the United States and thus found a higher than appropriate ratio for the adverse conditions. The authors respond however that, even if this were true, the more important number is likely theunderreporting of cases and on this point we agree.

Certification

The undersigned certifies, to our best knowledge and belief, that this petition includes allinformation and views on which this petition relies, and that it includes representative data and information known to us which are unfavorable to the petition.

Steven W. Mosher, David C. Morrison
Executive Director, Associate Editor