Talk:Mifepristone

U.S. fatalities

A girl in California died after taking the pill: [1] [2]. -- Jim Regan 20:18, 24 Sep 2003 (UTC)

Marcie i'm wondering what the risks are too...although eventually with ANY drug someone will die. I wonder if the section on chemical abortion can just be rerouted...i tried to write it then i noticed this had most of the info?

According to studies that I heard about on the safety and efficacy of this drug, it has a safety profile equivalent to penicillin (i.e., estimated 1 death per 100,000 users).

Can someone find a citation somewhere of where its being investigated for links to various cancers? That one line is uncited, and it seems a controversial enough assertion to demand being cited. SiberioS 07:06, 7 August 2005 (UTC)

It is being investigated for use against cancers. Looks like the pro-life lobby is spreading disinformation again. JFW | T@lk 07:26, 7 August 2005 (UTC)

The reference for cancer was produced by the American Breast Cancer Association and refers to Danish research "In 1997 researchers in Denmark published the results of a large, well-done cohort study of abortion and breast cancer risk.4 This study, which included data on 1.5 million women, avoided the problem of reporting bias by relying on data collected from abortion registries (i.e. medical records) rather than individual reports. This study found no association between induced abortion and breast cancer risk; women who had abortions were no more likely to develop breast cancer than women who had not had abortions. This finding was consistent among various subgroups of women; it did not differ depending on age at abortion, number of children, time since abortion, or age at diagnosis of breast cancer"

The breast cancer and depression argument is often used by anti-choice grouops without any uderstanding of the actual research.

Not sure how to edit this page. Only created this account to refute this erroneous information.

I think this page should be reorganised to discuss mifepristone pharmacology before all the politics. Lise 31st Janaury 2006

A more detailed description of how it works should be included.— Preceding unsigned comment added by 198.86.234.156 (talk • contribs) 18:07, 3 May 2006 (UTC)

Too many pro-choice links

The External links section is extremely biased in its coverage of websites dealing with RU-486, with only one link against the drug and the others being supportive of the drug and its use. Either some of these links should be removed or more pro-life/anti-RU486 links should be added; otherwise, this section's information is unreliable and uneven. Brisvegas 03:14, 19 February 2006 (UTC)

A more detailed description of how it works should be included. — Preceding unsigned comment added by 198.86.234.156 (talk • contribs) 18:06, 3 May 2006 (UTC)

Lots of wrong info on this article....

There is a lot of false info on this article, most notibly being the mortality rate, which the FDA says there are only 4 deaths that were reported, and they clearly say that none of them were linked to RU-486, and there is one death that is being investigated currently, though they allude to the fact that infection was the problem, not RU-486:

http://www.fda.gov/cder/drug/infopage/mifepristone/

Elsewhere on the FDA site, they say that in the 4 reported deaths where the women died of infection, all 4 were taking the drug vaginally, which is an off-label use. Meaning, the medication was never intended to be taken vaginally.

Whomever wrote this needs to learn how to research. —The preceding unsigned comment was added by 4.233.140.87 (talk • contribs) 02:44, 20 May 2006.

I disagree. I believe all of that info is covered in the article. The only thing we may need to qualify is that we say "six women in the US and one in Canada have died following medical abortions" which doesn't mean that mifepristone CAUSED the deaths. We may need to say "though the FDA has ruled mifepristone out as the cause" or something similar. Feel free to edit the article in whatever manner you feel will improve it. And also, you can alwas register a username. It's fast and easy (and free), and editors tend to take you more seriously if you aren't an anonymous IP address.--Andrew c 02:58, 20 May 2006 (UTC)

• i disagree--i think editors are entitled to anonymity if they choose, and i don't make any value judgements about editors who choose anonymity.

Cindery 21:20, 21 August 2006 (UTC)

Need reference for abortion death statistic

Said rate of deaths for illegal abortion was 1 in 3000. Depends on what year you're talking about. Prior to Roe v. Wade, there were something like 40 deaths from illegal abortions, and there were certainly more than 120,000 illegal abortions that year. Rate of death for illegal abortion depends on the year you're talking about, the country you're talking about, and the medical ability of the country. Antibiotics greatly reduced deaths due to abortions, both legal and illegal. Killua 13:12, 30 May 2006 (UTC)

As morning-after contraceptive

This article could do with information on the use of mifepristone as a morning-after contraceptive (which is not the same as the higher-dose abortifacient role; see e.g. discussion here.) I don't have the time to do it now - anybody feel like taking a crack at it? --Calair 04:24, 21 July 2006 (UTC)

depression and abortion

citing a position paper which has selectively interpreted selective studies doesn't "refute" anything--even the studies they cite claim women can experience some distress after abortion (it's not exactly a pleasant experience, physically or emotionally) no argument has been made to support the claim that all studies which find that women can experience distress/depression are claiming she has "post abortion syndrome." and you seem unclear on the concept of what claims psychological studies can make--they can never prove or refute anything.

what actually exists are studies with conflicting/a range of conclusions. while it does seem true that different side of the pro-life/pro-choice debate like to use conflicting studies to bludgeon each other in arguments, what i'm concerned about is NPOV for womens' sake. (women do not have to pretend that something doesn't hurt or doesn't cause psychological distress in order to be "pro-choice.") so a balanced view of both sides with a study from each seems reasonable. we could cite 80 studies, but 1) this isn't an article about depression and abortion 2) citing a debate is supposed to accurately reflect the existence of the real world debate. Cindery 18:23, 19 August 2006 (UTC)

I agree that this article isn't about ABC or PAS. However, you are the one that expanded both sections and seperated them, removing the APA reference.

• i separated them because they are very separate concerns--breast cancer and depression are NOT on par. (and were confusingly intertwined viz the refutation claim.)

there was a very minor expansion--a whole sentence--to present the subject NPOV style, with a study from either side and the suggestion that the real issue may be whether depression was a pre-existing condition.

I'd be satisfied with one sentence mentioning ABC and PAS and their lack of widespread acceptance among mainstream medical association, as long as each topic was wikilinked.

• i would not--the american medical association is not the ultimate unbiased arbiter of anything. (for example, they get a lot of money from bayer and so endorse bayer aspirin..) actual medical studies--not interpretations of them-- are NPOV/it's NPOV to include one from each side, anyhting else risks NPOV or expanding the section into excess focus on depression/abortionfor an article on mifeprex.

Cindery 19:30, 19 August 2006 (UTC)

I do not feel that this article is the place to bring out that debate. A side note, you also may want to familiarize yourself with Wikipedia:Citation templates and WP:CITE to help format your citations. It is generally bad form to simply add an external link instead of a proper citation. I'll work on the few that are in this article and you can look at the diff to see what I have done. --Andrew c 18:33, 19 August 2006 (UTC)

Did you read those two links? Did you see what I did to convert your EL to proper citations? Do you have any questions about how it is done? If not, then I'd urge you to convert the links you already added to the cite.php format (i.e. using <ref> tags) and citation templates. I didn't mind converting the few I did the other day, and I don't mind answering questions you may have, but if we are trying to make a good article, we should be consistent on how we cite our sources.--Andrew c 21:09, 21 August 2006 (UTC)

• you know, someone else who was much nicer about it has recently helped me learn how to do that--i fixed citations on another article. perhaps i will get around to converting some of these. the massive amount of time i have put into exhaustive pubmed searches to find citations to greatly improve the article has taken up most of my wiki-time lately. feel free to improve the article yourself by converting refs, researching them etc.

Cindery 21:18, 21 August 2006 (UTC)

I apologize if my tone offended you. I was seriously asking if you read the links, and I was seriously asking if you needed help. If asking for help is not "nice", then you aren't going to like what I have to say next. If you already know how to cite references properly because someone else had to inform you, then you have no excuse for not doing it here? Why contribute at all, if someone has to go behind you and fix everything? I understand that you feel the content you are contributing is more important than the way it if referenced, but you have to remember that every time you hit "save page", the content goes out to the general public. Here is a tip: you can always put your edits in a text file or a wp:sandbox and not upload the content until it is ready (this will also help with avoiding the clutter in the page history).--Andrew c 21:45, 21 August 2006 (UTC)

• "why contribute at all?" seems to be your attitude towards people who contribute and don't completely agree with you--you nitpick about how they contribute. i think you should save bickering/nitpicking for personal talk pages, so as not to grievously bore everyone else. or better yet, spend some time improving the article by converting refs if that's so important to you, instead of bickering and nitpicking--it's not "collaborative."

Cindery 22:07, 21 August 2006 (UTC)

You seem to have a misunderstanding of NPOV, Cindery. It has an important qualification, undue weight, which holds that while we should attempt to cover the entire range of a topic, we should do so in proportion. Unfortunately, science isn't a moral debate, and you can't err on the side of neutrality by simply attempting to "weigh both sides equally." If the majority of scientific opinion falls on one side of the fence, you would actually do a disservice by presenting a minority opinion of as being of equal validity, or giving it "equal time," because this would skew the picture of the real debate. For instance, if we were working on an article about the solar system, it would be inaccurate to be present geocentrism as being on par with heliocentrism.

I do not intend to comment on the findings of any ABC or PAS related study. However, I question the addition of the two large sub-sections on abortion-breast cancer and mental health. These topics are already covered in part at Abortion, and in full at Post-abortion syndrome and Abortion-breast cancer hypothesis, so there is no reason for such reiteration here. Thus, I am removing these two sections, as they are not topical, and diminish the quality of the article significantly. -Severa (!!!) 21:34, 21 August 2006 (UTC)

i would agree that depression doesn't need to be addressed here, but i felt it would have been rude to delete the section rather than try to balance/improve it. i will leave it deleted--i don't know if andrewc will object. i am putting breast cancer back, becuase the concern regarding 19 nors and elevated risk is significant but i think it is good to frame it in the larger discussion of studies on abortion/breast cancer risk, so as not to appear alarmist.) i will just ignore the patronizing/hostile tone of your illogical application of "moral debate" vs. science to a discussion of depression and abortion (or any psycholoigal studies of traumatic events). Cindery 21:56, 21 August 2006 (UTC)

I agree that breast cancer is relevent because of the studies involving the particular steriod in mifepristone. Now is this the same thing as the ABC hypothesis? I think not. I am torn over whether we still need a sentence mentioning and wikilinking ABC and PAS. As I said above, I don't feel like more than one or two sentences is really necessary, but for ballance it may be necessary to say that there are some people that advocate these theories. But then again, it is covered in 3 other articles.--Andrew c 22:07, 21 August 2006 (UTC)

I advise that you consult WP:AGF. Twice in a single discussion you have taken offense to explanations of policy. I did not mean to suggest that evidence for or against PAS or ABC were conclusive; I merely intended to note that your functional intepretation of NPOV was flawed (as evidenced in the statement, "it's NPOV to include one [study] from each side"). While a journalist might achieve neutrality by "weighing both sides equally," we, as an encyclopaedia, cannot, given the rule of undue weight. If the consensus among authorities on an issue is clear, we must present it as such, because it would be POV to suggest uncertainty where there is little to none. -Severa (!!!) 22:31, 21 August 2006 (UTC)

...also note that i didn't say it was npov to include one study from each side in a vacuum, but specifically with regard to this issue in this context. (i am already on record elsewhere pointing out that citing holocaust deniers as reasonable stakeeholders in a discussion of the holocaust is not neccesary for npov...) take care that your "explanations of policy" observe the wiki policy of assuming good faith, and are not merely gratuitous harassment/attempts to bully. thank you. Cindery 22:43, 21 August 2006 (UTC)

I am sorry that you find my policy reminders "bullying" and "patronizing." I did not intend to come across as overly critical, and, perhaps, I should have checked your edit history so that I would know to apply WP:DBN. However, I find the accusation that I have somehow been hostile confusing, given some of your comments toward Andrew c:

"why contribute at all?" seems to be your attitude towards people who contribute and don't completely agree with you--you nitpick about how they contribute. i think you should save bickering/nitpicking for personal talk pages, so as not to grievously bore everyone else. or better yet, spend some time improving the article by converting refs if that's so important to you, instead of bickering and nitpicking--it's not "collaborative."

Please consult WP:CIVIL and WP:NPA to learn precisely what constitutes hostility on Wikipedia. -Severa (!!!) 23:15, 21 August 2006 (UTC)

same to you. (note also that he actually said "why contribute at all?") your summary deletion based on flawed reasoning, determining that sections are irrelevant without checking edit history of article, making assumptions without checking someone's edit history and giving abc lectures about heliocentrism--all quite patronizing and rude. Cindery 23:17, 21 August 2006 (UTC)

Please, explain to me, how have I been patronizing and rude? I do not recall suggesting that you are nitpicking, bickering, or that your posts bring grievous boredom to those who read them. The harshest thing I said was that I believe you to be under a mistaken impression of NPOV, which is far from a personal attack, even if my underlying logic was faulty. Many of the misunderstandings on Wikipedia are the direct result of failing to assume good faith. Andrew c's "Why contribute at all?" lapse only occured after you had made a defensive comment which assumed bad faith on his part (emphasis mine):

"you know, someone else who was much nicer about it has recently helped me learn how to do that."

The sentiment expressed in your response to my first posting on this Talk page was as follows (emphasis mine):

"i will just ignore the patronizing/hostile tone of your illogical application."

The presumption of bad faith carried into your follow-up post (emphasis mine):

"take care that your "explanations of policy" observe the wiki policy of assuming good faith, and are not merely gratuitous harassment/attempts to bully. thank you. "

If you continue to assume bad faith, especially so systematically, the assumption will become self-fulfilling prophecy. It is only natural that people will counter defensiveness with defensiveness. If you want to participate in the writing of this article then it would be better to approach it in a manner more conducive to cooperation. -Severa (!!!) 00:14, 22 August 2006 (UTC)

i can see that it is very difficult for you to admit that you were wrong. maybe you should cool off for a while and address me on my talk page if you still feel that there's something to discuss, as this is the discussion page for mifepristone, not belabored off-topic arguments/misunderstandings about anything else. Cindery 00:41, 22 August 2006 (UTC)

You cannot conveniently defer attention from yourself by continued finger-pointing. Especially when it has not really been established how, precisely, I have been rude to you, as you have been systematically discourteous to Andrew c. -Severa (!!!) 01:01, 22 August 2006 (UTC)

reply will be on "severa"'s talk page, to avoid continued belaboration of off-topic on mifepristone discussion page. Cindery 01:33, 22 August 2006 (UTC)

comparative fatality

i removed the previous citation for statistical comparison because 1) it was out of date 2) it cited another source for its numbers, and that source didn't cite any source 3) i believe it is wrong. both alan guttmacher institute (whose primary resource is journal of obstretics) and the new england journal of medicine cite that the risk of fatality in surgical abortion at 8 weeks is .1 in 100,000/one in a million. the michael greene article from the NEJM is available online, but only with registration, so i found it reproduced at another site and included that link instead. (greene also notes that 460,000 doesn't necessarily equal 460,000 procedures--he thinks it is far less--but in the absence of reliable data about how many procedures it does mean i have left that number without qualification.) Cindery 06:15, 21 August 2006 (UTC)

is mifepristone+misoprostol the same as miscarriage/spontaneous abortion?

based on facts that i am aware of, they are similar but not the same (average bleeding/length of bleeding in spontaneous abortion is less than in medically induced; medically induced has drug-related side effects; d&c is more likely to be performed for spontaneous...) here is one article:

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1120430

the description of medically induced in strictly taken from the product insert--i will note that as citation. if you want to compare spontaneous vs. induced abortion, feel free--but please provide citations, and note in your comparison both the similarities and differences. a direct conflation isn't accurate in terms of symptoms/mechanism of action (or standard medical attention/management). Cindery 20:32, 21 August 2006 (UTC)

breast cancer risk

this is the last time i am going to replace this info, per the rules about reverting. if it is removed, i am going to flag the article for accuracy.

Well, I initially supported including the information regarding the synthetic steroid. However, I have read the paragraph closely again and I cannot think of a reason why it should be included. It has nothing to do with mifepristone. The one cited article doesn't deal with mifepristone. It deals mainly with HRT, and specifically says "The use of progestational agents in pregnancy... does not cause concern in relation to BC risk." So I don't see how an journal article that doesn't deal with this drug, that doesn't mention the sort of single dose application used normally with chemical abortions, and specifically mentions the lack of risk these agents pose during pregnancy, has anything to do with this artlce. The rest about the ABC hypothesis and the NCI is off topic and covered in other articles. How does removing that section throw the accuracy of this article in question? --Andrew c 22:39, 21 August 2006 (UTC)

• i would suggest that you research the subject of exogenous hormones and breast cancer in order to be able to understand the significance of the hrt studies. also to understand the complicated interplay between PRs progesterone receptors) and ERs (estrogen receptors) and breast cancer, and how an anti-progestin might proliferate estrogenic effects, thereby proliferating breast cancer cells. the most important thing is that "no long term studies of the carcinigenicity of mifepristone have been performed," and so the breast cancer risk is unknown, but there may be concern.

Cindery 22:53, 21 August 2006 (UTC)

Andrew's concerns notwithstanding, if this is the case, I think it might be useful to explain within the article how it is the synthetic hormones which might pose a cancer risk with mifepristone. It might be unclear to readers that this risk factor is independent of that proposed by the abortion-breast cancer hypothesis. However, I do not think this would necessitate that we discuss the history the ABC hypothesis, related studies, or the NCI workshop at length. It is already covered in part at Abortion#Breast_cancer and in full and abortion-breast cancer hypothesis. -Severa (!!!) 00:51, 22 August 2006 (UTC)

I agree. The ABC hypothesis stuff doesn't seem to fit here. I voiced my concerns over the cited study. I was thinking it might be OR to claim a study that doesn't mention mifepristone posits a BC risk. However, the way it is phrased regarding how no studies have been performed, and if we clarify the synthetic hormone bit, I think we could come up with a couple sentences to cover this issue. So the question to Cindery, would you conceed those extra sentences about the ABC hypothesis, if it was replaced with a wikilink to the main article?--Andrew c 01:54, 22 August 2006 (UTC)

i do not object to the way breast cancer risk is currently displayed in article (although i don't think a longer explanation providing context/moving it down so there is room for other contributors to add is bad idea either). as for citation to explain possibility of mife-bc risk, this citation may be better:[3] perhaps a sentence to explain that estrogen is associated with breast cancer, hence anything that enhances estrogen exposure might increase risk of breast cancer would explain better to readers--but that is only one theory. no one knows what causes breast cancer, hence all risk factors are speculative, blar blar. an "adequate" explanation could get very very complicated, and i think the important things are 1. no studies done on carcinogenicity and mifepristone 2) it's hormonal therefore there may be some cause for concern. i actually think less emphasis is placed on it when it is in a separate section much further down, than when it is in the "side effects" section. it's not a side effect, it's a possible risk. Cindery 02:22, 22 August 2006 (UTC)

I've added a note to the ABC paragraph to put potential risk in context. - RoyBoy ⁸⁰⁰ 13:54, 22 August 2006 (UTC)

i think several pages about the possible risk of breast cancer and hormones might put the news article you have cited in perspective (please note that most breast cancers are estrogen receptive, not progesterone receptive, and that even progesterone is mediated through the ER in hormone-sensitive tumors.) you should at least read the breast cancer page, if you have not. feel free to find one of the actual medical studies this article cites, put it in context with the 1) the number of hormone sensitive tumors 2) the subsection which is progersterone-sensitive. it will be a long piece of writing...(i'm not in favor of overstating or understating the possible significance of an estrogen-proliferating hormone on breast cancer.) take care also to note the differnece between news articles and medical studies/the body of medical knowledge (i.e., news articles are often based on press releases from drug companies, and do not reflect current bodies of knowledge accurately, but selectively trumpet this or that out of context.) Cindery 14:25, 22 August 2006 (UTC)

I didn't add the news article; that was done after me by another user. I did however reinsert it and used your point (with a reference) to give it appropriate context. I agree with your analysis. - RoyBoy ⁸⁰⁰ 15:56, 22 August 2006 (UTC)

my apologies for erroneous assumption.

Cindery 00:56, 23 August 2006 (UTC)

Misoprostol

This article is not misoprostol and is not Chemical abortion. I cannot think of any reason to include extensive information about another drug in this article. The edit summary that put this paragraph back in says replace highly relevant misoprostol info/mifeprex is not used alone/this is very little info re misoprostol. I do not see how it is highly relevent. This article should be about what the title says it is. If we want to combine mifepristone and misoprostol, we can do that. If we want to work up most of this information in the more releven chemical abortion article, we can do that as well. However, I still need more of a reason why to include information about another drug in this article.--Andrew c 22:45, 21 August 2006 (UTC)

i would say there is probably too little info re misoprostol, if you look at how much of the article is not about mifepristone, but about mifepristone used in combination with misoprostol for medical abortion. i think the use of mifepristone for medical abortion is its most noteworthy use, and therefore it makes sense that much of the article is about that, and therefore some info about misoprostol has to be included (though not as much as at misoprostol article). (i have been meaning to add some info, such as what other drug combos the fda has approved, and a link to the citation for that, to show that it is not completely abnormal/not specific to this case.) i notice that you do not object to the many mentions of misoprostol viz oral/vaginal and the implications that has. what you removed was info about the fact that misoprostol can cause uterine ruptures and is not approved by the fda for labor induction. i think that's more than relevant and valid info, it's scientific/neutral, and that an objection to including it is pov.Cindery 23:03, 21 August 2006 (UTC)

speculative comparative breast cancer risk factors

i'm not sure what the point of stating that a previous abortion mitigates the any possible risk presented by mifepristone? breastfeeding, having a baby, exercise, veganism, moving to japan, avoiding artificial light--it would take pages to list all the possible/associative mitigations-of-risk. and all mitigations must be stated conditionally/as associations. as we do no know what causes breast cancer, we can only merely observe what it is not associated with...nothing can be definitively causally stated... Cindery 16:41, 22 August 2006 (UTC)

It wasn't causally stated; it is clear limiting ones exposure to hormones and pseudo-hormones is beneficial and reduces ones risk. Everything listed above effects hormones... having an abortion earlier reduces ones exposure to hormones. That is not speculative, hence getting an earlier abortion is beneficial I mean limits the ABC risk; which in turn mitigates the mifepristone risk within the abortion context. We don't need to spend hours listing mitigations-of-risk; this point adds context to the immediate subject mentioned at the beginning of the paragraph; ABC and use of mifepristone for abortion. - RoyBoy ⁸⁰⁰ 17:26, 22 August 2006 (UTC)

you did actually make an unconditonal rather than a conditional statement, and posit it causally. and endogenous vs. synthetic exongenous hormones would be another very long complicated discussion (are you familiar with the differing carcinogenic potential amongst the progestins?)

just listing all the relative hormonal risks would be quite a list (not to mention that giving birth before age 30 and breastfeeding appear to offer most protective of all the reproductive events...)

it seemed sorta to me like you think you're being cute or that i will be annoyed by a favorable claim for abortion--barking up wrong tree. go read Barrington Hall. Cindery 20:00, 22 August 2006 (UTC)

Excuse me? Why do you keep listing more factors for breast cancer, are you trying to be cute? (as I wrote the majority of the ABC article, I'm aware ad-nauseum to factors for breast cancer, if you keep bringing up factors... I'll keep getting annoyed) I will repeat this again, those don't add context to this paragraph/section that discusses ABC, mifepristone and abortion. While I'm not an expert on progestins, I am keenly aware there are a lot of hormones out there and more pseudo-estrogens (as I'm calling them), and that they have various impacts and co-relationships with each other and on breast tissue. I'm not barking up any tree, but perhaps I should as that may accomplish more. As to conditional statements, I'll defer to you as my syntactic skill is weak... but that was not the intent of my addition. Anyway, another sentence comparing impacts of pseudo-estrogens and natural estrogens is great (as it provides an opportunity to wikilink two important concepts... but they are likely linked elsewhere in the article), but I cannot see how that makes my statement wrong or original research in any way. At worst it may have been confusing, that means it should be tweaked not removed.

The point I want to get across is clear, having an abortion early is good as far as abortion breast cancer hypothesis is concerned. Mifepristone is one way to get an early abortion... so the drugs breast cancer impact isn't the only consideration when using it. That's worth noting. Right? - RoyBoy ⁸⁰⁰ 00:53, 23 August 2006 (UTC)

you need to do some research on the diff between exogenous/endogenous progestins--that will clear up your misunderstanding. perhaps i overestimated your knowledge of the subject because i *did* glance o at your lengthy contributions to abortion/breast cancer. perhaps you're not up on the synthetics/the difference since you've only studied endogenous?

i think the point is not "how we can we make a mifepristone article be about breast cancer?" (xenoestrogens really far out/irrelevant) but how can we appropriately note --in proportion to article so as not to overrate or underrate significance-- that no studies have been done to assess the human carcingenicty of mifepristone. that is a salient fact. the first generations of the people who take this drug are the test subjects. Cindery 01:06, 23 August 2006 (UTC)

Perhaps. My main exposure (if you will) to synthetic steroidal estrogen research was when I needed to put the HRT study in context for confounding factors. So long ago I perused the Wikipedia article on it, looked at it now and it doesn't elobarate on those types. Apart from that its been the natural pregnancy cocktail I've been focused on. Apologies for my ignorance, I'll try to catch up. - RoyBoy ⁸⁰⁰ 06:34, 23 August 2006 (UTC)

First of all, should side effects not found on the product label [4] be included in that section? Specifically, I feel the breast cancer paragraph is misplaced. I think it fit better in the controversy section. Next, while this is related to BC, it deals with the "Other Possible Uses" section. Should any of this information be included:

• "As it contains no oestrogen it should not promote breast cancer, and by inhibiting progesterone it is thought that it may even reduce the risk... The effect on breast cancer is predicted because some kinds of breast tumour appear to be sensitive to progesterone, so blocking its action should inhibit their growth. “Certain breast cancer studies suggest that progesterone can promote cancer as well as oestrogen,” Professor Baird said. “There are also some preliminary clinical data on women with advanced breast cancer which suggests that this could be helpful.”"[5]

-Andrew c 18:15, 22 August 2006 (UTC)

you still don't seem to get it--inhibiting progesterone increases estrogen. that article is basically a press release making false claims for a new birth control pill that doesn't exist.

• i absolutely agree breast cancer risk should be noted as mere possibility. noting anything else requires a lengthy explanation of why estrogen-dependent tumors comprise the vast majority of cases, what an experimental in vitro study is and how little it means, etc.

perhaps what should happen is that the statement per the product insert/the clinical trials which danco was required to disclose:"no long-term studies have been performed to determine the carcinogenicity of mifepristone" bolded and italicized--anyone who takes this drug is a lab animal/ assumes the risk entirely of any and all cancers, no long-term epidemiological studies have been done, period. i think the possible risk posed by exongenous hormones which cause estrogen to dominate is not, say, lung cancer. but i'm fine with the totally inclusive warning. as breast cancer is the second most commone cancer for women, it will definitely be implied. Cindery 19:05, 22 August 2006 (UTC)

plagiarism

The following is lifted verbatim from the product label:

There are no data on the safety and efficacy of mifepristone in women wih chronic medical conditions such as cardiovascular hypertension, hepatic, respiratory, or renal disease, or insulin-dependent diabetes mellitus. Women who are more than 35 years of age and who smoke 10 or more cigarettes a day were excluded from clinical trials.

No long term studies to evaluate the carcinogenic potential of mifepristone have been performed.

It needs to be altered to avoid plagarism, or quoted.--Andrew c 21:23, 22 August 2006 (UTC)

animal in vitro/human

Quoting text has it's uses, and sometimes it is hard to paraphrase and summarize certain content (such as lists). However, I think the recent edits have gone out of hand. There is way too much jargon and content that isn't encyclopedic or accessible to lay audiences. Furthermore, elipses are not being used to indicate breaks and edits not found in the original text. Wikipedia is not a primary source, and quoting so extensively the technical language from the Mifeprex label is degrading the quality of this article. I request any editor's help in summarizing the key points under the "In Vitro and Animal Studies" to avoid this problem of quoting a technical source so extensively. Thanks for your consideration.--Andrew c 00:00, 23 August 2006 (UTC)

i think the in vitro/animal studies should be moved down, and the stats re humans should stay near the top? right now i would say the quotes are "in progress" toward an eventual adapation, and the stark neutrality of the lang is good place to start. mifepristone product insert not copywright material, btw. Cindery 01:11, 23 August 2006 (UTC)

I was just a little concerned over the current state of things. If it is in progress, hopefully soon it will be improved. However, not to butt heads again with you, but the language is not neutral. It comes from a medical POV and clearly is full of jargon that is not accessible to lay audiences (i.e. "genotoxic", "estrus cycles", "Teratology", etc). There is a difference between wikipedia's NPOV policy, and a scientific POV or a No-POV policy. As for the copyright, if it was produced by the US government, then most likely it is in the public domain. But if it was produced by Danco, it may be copyrighted. Do you have any more information to help clarify this issue?--Andrew c 01:24, 23 August 2006 (UTC)

I wouldn't mind attempting to rewrite the package insert information in a more accessible way. Also, it would seem preferable, to avoid having such a large chunk of the article being a direct quotation. However, being that we are dealing with a technical subject, the retention of some technical terms will be unavoidable. There is no substitute for a term like "estrus cycle" — but that is the purpose for which Wikilinking was invented. "Genotoxic" could be simplified to "mutation-causing substance" or else Wikilinked like estrus cycle. I don't believe in "dumbing down" a technical subject, by any means, but some smart editing should make the information both accurate and accessible to a wide readership. -Severa (!!!) 01:57, 23 August 2006 (UTC)

4 hour waiting period

is it true that there is a four hour observation/waiting period in most other countries which use mifepristone--all of europe, china, but not U.S? Cindery 22:38, 22 August 2006 (UTC)

i'm seeing 6 hours for new zealand, and four hours for china and europe-but have not had time to search exhaustively. it looks like the standard procedure is that after the second drug is given, there is a waiting period during which the conceptus is expelled, and emergency medical care is available. if conceptus is not expelled during the waiting period, surgical procedure is offered/advised. most women expel the conceptus during the waiting period, or opt for surgical if thye have not. a tiny minority refuse surgical if conceptus not expelled during waiting period. i think this is significant/should be mentioned in article.

i think this could be mentioned in an expansion of the description of how the drug regimen works, which should also make it clear that there are 3-4 visits/steps. Cindery 19:18, 24 August 2006 (UTC)

Sounds like good information, and the international perspective is always welcome.--Andrew c 20:02, 24 August 2006 (UTC)

Mortality rate

We list the number 6 in 460,000. I have been unable to find a source that lists that number. The first cited source says "less than 1 per 100,000". The 3rd cited source lists the more than 460,000 number, and mentions the 5 deaths. As far as I know, mortality rates are usually given in a per 100,000 number anyway. Do we have another source, or should we change it to reflect the already cited sources? --Andrew c 21:52, 22 August 2006 (UTC)

1. 6 is the number of fatalities according to FDA (which notes that they estimate they receive less than 10% of all serious adverse reactions) 2. per NEJM (article by pro-choice Dr. Michael Greene) 460,000 is the number cited by Danco, which Greene believes is too high a number (read article for his explanation.) i also included the danco press release citing that number.

3.6/460,000 is the most favorable possible statistic i could find, and does not meaningfully account for estimate of underreporting, or any account of greene's obervation re Danco's calculation of 460,000. if you want to cite the numbers 1.34 per 100,000, as well, go ahead. per greene, the appropriate comparison is for surgical abortion at 8 weeks gestation--that's approx 13x the risk, "may be higher." Cindery 22:17, 22 August 2006 (UTC)

My only concern is verifiability. If someone wanted to look up that specific number, they'd have no place to turn because it is a synthesis of sources (aka original research). Why don't we simply use a figure already found in one of our sources. I seriously doubt finding an estimate mortality rate for mifepristone requires OR. I could not find the numner "1.34" in Greene. I did find this "These figures would suggest that the risk of death from infection is less than 1 per 100,000." So does this figure ignore the one death due to an ectopic pregnancy? Anyway, can we find a source that is more specific? Or should we leave it vague? I think its important to note what our sources note, that is that chemical abortion is 10 times more deadly than a comparable surgical abortion, however it is also ~10 times safer than live birth. I find it odd that its hard to find a simple mortality rate figure for mifepristone, but it clearly isn't our job to try and calculate that and publish the number here for the first time.--Andrew c 22:32, 22 August 2006 (UTC)

i'm not sure simple arithmatic is OR, but to avoid confusion that is why i cited 6/460,000--those numbers are from verifiable sources: FDA, Danco. those links are provided, people can look it up quite easily. if you think converting 6/460,000 is OR, by all means don't do the math. i'm not interested in being alarmist/overstating the risk, but even by lowest estimate (it's improbably low, actually) the risk is more than 10x surgical. Cindery 22:47, 22 August 2006 (UTC)

This is a sticky issue and I'd like a third opinion to weigh in, but I still feel that if we have a single figure that is verifiable in our sources (instead of combining 2 numbers), it is clearly superior. Wikipedia shouldn't be the only place that a precise mortality rate is mentioned. And as I stated above, I agree completely that we should state the risk is ~10x that of surgical.--Andrew c 23:48, 22 August 2006 (UTC)

i think it's not a matter of opinion--anything other than the most accurate verifiable numbers to date is grounds for accuracy objection. (probably anyone who wants to make an issue of it has grounds for an accuracy dispute based on how low the the risk has been calculated, even if we agree...) Cindery 00:06, 23 August 2006 (UTC)

If there was an article about the trees of Monroe Park, I could easily walk down the block and count the trees. However, it would be against wikipedia policy for me to publish that number in that article because it would be original research. Obviously, my number would be the most accurate figure available, but without it being reported somewhere else first, it violates policy. Yeah, we might not like it, but we may have to sacrifice accuracy in lieu of verifiability and no original research. That's all I'm saying. Now, if we have a source that has a figure, I propose we use that. And if it isn't precise, well it isn't precise, but it is verifiable. The most favorable solution would be to find a source that published the 6 in 460,000/1.3 number.--Andrew c 00:19, 23 August 2006 (UTC)

i think maybe you should sleep on whether doing fractions is original research... Cindery 00:30, 23 August 2006 (UTC)

Another part of this issue is, mifepristone has been around for about 17 years in Europe. Your figures only deal with Mifeprex in the US (and Canada?). Wouldn't data from the past decade in Europe be equally as important to this article? Maybe that is why the mortality rate is always listed as "less than 1 in 100,000" despite your math. This is why OR can be tricky. What seems obvious to us at first, is deceptive because it doesn't consider the bigger picture.--Andrew c 00:45, 23 August 2006 (UTC)

data is not available for elsewhere, i checked. note that i didn't include worldwide fatalities, only american. (UK underreporting--according to report dealing with 2 fatalities--is much worse than US. they stated, "if there's 2, there's 20)

i don't think there was ever any doubt that we were talking about US numbers, would qualify them as such. the WHO hasn't come along and done a worldwide epidemiological study, so world numbers can't even be guessed at.

absence of world numbers doesn't mean US numbers can't be calculated (or that, like clinical trials, there are any compelling reasons that they should not be comparable to other developed countries. but, no doubt developing countries have more fatalaties to report...) Cindery 00:53, 23 August 2006 (UTC)

Interesting point. Qualifying them as US numbers seems appropriate. Anyway, your protests made me reconsider my OR accusation. So I posted Wikipedia talk:No original research#New synthesis.2Fis this OR.3F. Feel free to correct any mistakes I made, present your own side, and read the replies.--Andrew c 00:56, 23 August 2006 (UTC)

i wouldn't call them "protests," i would say i am trying to reason with you. Cindery 01:27, 23 August 2006 (UTC)

Ok, the discussion at the talk WP:OR page seems to support having a citation of the number. There were only 2 editors that supported the figure being in the article. One editor's comments seemed to come from resentment of the policy in general, and the other editor only has a single edit. On the other hand, there were only 3 people who supported my OR assessment, but they all seem to contribute to that page regularly. So it still is a sticky situation. I think everyone would agree finding a citation of a number would be the best thing. However, until then, I'd propose a compromise that makes it clear that we are not listing an official mortality rate. Something like: Since it's 2000 FDA approval, there has been a total of 6 deaths in the US following mifepristone/misoprostol use, while Danco labs has shipped a total of over 460,000 doses. However, as the anonymous user pointed out back in May, this wording is confusing because the cause of death is up in the air (and mifepristone has been ruled out in some cases by the FDA, no?). The point being, we can relay this information in a NPOV manner, without synthesizing it into a new, unpublished mortality rate. What do people think? Anyone come up with a better source yet?--Andrew c 19:45, 23 August 2006 (UTC)

deaths from anesthesia, uterine perforation, infection in surgical abortion are not excluded from the mortality rate, i.e., they are not directly caused by surgical abortion, they are risks associated with it. same for every other drug. and that's where the mortality rates comes from...

i think you should take a look at the CDER stat reports for abortion (included here for the 5.2 stat on proportion of abortion which is medical). the CDER compiles abortion stats every two years, with what looks like a four year lag time on analysis/release, and notes 1)underreporting 2) omission of whole states as accuracy deficits in their reports. but these numbers are cited as reliable (i'm not objecting--for percentage of abortion which is medical, it was the most accurate data i could find. afterwards i checked and saw it is the exact same statistic quoted at abortion, so i figured that was the best they could find, too.) but i put "data is limited" to qualify.

also take a look at david kessler's speech upon the inauguration of "medwatch" in 1994 re underreporting. the point being, admissions of huge probabale inaccuracy do not prevent the FDA/CDER from noting stats from best available data, with the open caveat that they're inaccurate. the acceptable standard of data is "most accurate available," not "unquotable unless believed to be 100% accurate." it's sort of preposterous to even make the argument that the newest data available should not be quoted because it is probably not 100% accurate, in favor of reversion to the old data--which was never accurate in the first place. inviolable accuracy isn't a place that a claim can be staked viz any of these numbers--i think it's "most likely to be most accurate." it would be interesting to look at how, say, the death toll in iraq is calculated viz the lag time in govt. reports...are field reports noted in press added to previous known number? when they say, "this brings the death toll to <blank>" where are they getting that number? if we reported the number from the press, and quoted a statistic from the govt. about how many enlisted people have been sent to iraq, and compared those numbers to vietnam, would that be original research? that sort of begs the question less "is it orginal research?" than "why make a comparison?" the mortality rate in this article for medical abortion was originally compared to: mortality rate for surgical abortion, mortality rate for surgical abortion past 8 weeks gestation, mortality rate for childbirth, and mortality rate for taking viagra or claritin. (i agree with David Green that the appropriate comparison is between two methods of abortion at 8 weeks gestation. but i'm not so sure there's an absolutely indefensible argument for making any comparison.)

you should also probably look at the facts surrounding wider use of a drug--problems that can occur only in a large statistical population do not necessarily show up in clinical trials of 5,000 people. (total in the french and us submitted to FDA in 2000) that's why there's postmarketing surveillance... but postmarketing surveillance is severely hobbled by underreporting. if 6 fatalities show up in wider use, that's significant. not even deaths are always reported--holly patterson, for example--neither the hospital where she died or planned parenthood reported her death to the FDA. it was reported to the FDA because it made the news/by her family. the FDA says, less than 10% of all serious adverse reactions are reported--they don't say, "except for deaths," or, "only for one type of drug." european/developing country postmarketing surveillance is believed to be even worse than US. (that's why 600,000 in europe without fatality/adverse reaction stats doesn't mean much. if you could get postmarketing surveillance stats, we'd have to verify who per which parts of the 600,000 had any postmarketing surveillance, and if the quality was believed by anyone to approach the US standard of less than 10%.)

i will go and take a look at what the underlying data was for 1 in 100,000, if it's available. i suspect that it's from the clinical trials, and that it accounts for heart attack death(s) from the previous 2nd prostaglandin drug. which would make it innacurate in a number of ways--old, only from small population, associated with risk factor not associated with current formulation in use.

per your, "this is the american data from.."etc --i am not at all against contextual qualifications for statistics and looking at where the numbers come from to better know what they mean. i don't know that that's a wiki standard, whenever a statistic is quoted, to break it down, contextualize, and qualify it. (but perhaps it should be.) that would mean the 1 in 100,000 should probably be qualified as "these are the statistics from clinical trials of approximately 5,000 french and american women, over the age of 18 and under the age of 35, who did not have (long list of medical conditions controlled for). 5,000 is not believed by anyone in the medical statistics profession to be a number large enough to predict possible adverse outcomes in a larger population."

i am also very much in favor of greater public awareness of gross underreporting of drug adverse reactions, and the so- sketchy -it's -nonexistent practice of postmarketing surveillance. (i think people think someone somewhere has an office, a staff, and is carefully keeping track of what happens when a drug is released into a wider population than it was tested on;that postmarketing surveillance means data about the drug is being compiled that adds to our knowledge of it. or that release into wider population means we get anything approaching accurate information about what happens in the larger population; that the questions posed by clinical trials are answered in the postmarketing surveillance. what actually happens is that doctors, clinics, and patients are supposed to voluntarily submit reports about only the most serious adverse reactions. and they do so less than 10% of the time--FDA estimate, up from less than %1 in 1994. there is no enforcement system whatsoever. and no one doublechecks any records to see if adverse reactions were not reported. if you go to the hospital and drop dead of a heart attack, the doctor will probably report your cause of death as "heart attack," not adverse drug reaction, or possible adverse drug reaction, even if you were taking vioxx. (and why wouldn't he? he's not analyzing vioxx; it's not his job. and what if you came in unconscious and he never knew you were taking it? what if he had no reason to suspect vioxx? there's 101 perfectly good reasons for him not to report it that aren't even vaguely bogus--it's an inherent flaw of postmarketing surveillance.) but, if your family doesn't make an issue of it, report it to the FDA, and if you are not mediagenic, no one will ever know your death might have been associated with vioxx/ that there was a "Vioxx death." in a clinical trial, every aspect of your death would be analyzed, and it would be counted as a fatality associated with the drug. in real life, no one is looking that closely. (that *is* pretty much why the FDA takes something like 6 deaths very seriously, why canada would halt testing after one death, why the uk would say "if there's 2 there's probably 20.") i don't think the general public really understands postmarketing surveillance, etc. i think they think, well, people have been using it a long time and i haven't seen anybody dead on the news. or: people have only been using it a short time and now they're dead on the news. that, plus their anecdotal personal experiences comprises the sum knowledge about a drug from which they form opinions. but if they come to wikipedia and read about this drug, they could get much better information--not just the numbers, but info about what the numbers mean, where they come from, so hopefully they can make decisions based on more than anecdotal experience/what selected events happen to make the news.

anyway, i would like to include something in the article regarding the likelihood that 6 isn't an accurate number, without too long/unwieldy an explanation of what postmarketing surveillance is/what underreporting is, etc. Cindery 23:51, 23 August 2006 (UTC)

No original research please

The following violates the official no original research policy of Wikipedia, specifically no synthesis of published material serving to advance a position:

There may be some concern regarding elevated breast cancer risk and 19 nortestosterone steroids.

Although it has been reported in one small study that mifepristone might have experimental value to minorly affect breast tissue in vitro in the least common kind of hormone-dependent breast cancer, systemic hormone therapy is of little value, and mastectomy/lumpectomy and chemotherapy are the effective standard means of treatment.[6]

Mifespristone is an anti-progestin which causes temporary estrogen dominance.

Estrogen dominance is associated with increased breast cancer risk.[7]

If there are reliable published sources representing a scientific consensus that "there may be some concern regarding elevated breast cancer" when using mifepristone, please cite them.

Per Wikipedia, "The scientific consensus can be found in recent, authoritative review articles or textbooks and some forms of monographs."[8] 68.253.177.250 01:46, 23 August 2006 (UTC)

As stated above, I agree with this. Wikipedia cannot be the first place to publish that mifepristone may increase BC risk. If this information is a synthesis or analysis of multiple sources, then it fails OR. All claims, especially controversial or disputed claims need to be WP:V. I think we have the WP:RS part down fine (if anything, maybe a bit overboard with the primary sources), but for this one claim, it may fail verifiability and original research.--Andrew c 01:53, 23 August 2006 (UTC)

Agreed. The point is, if we are going to suggest a causal relationship, even a logical one, we're going to need at least one peer-reviewed, academic study which advances the claim to cite. Take, for example, vaccine controversy, which lists studies that have explored the supposed link between vaccines which contain mercury as a preservative and autism. Sure, given the fact that mercury exposure can cause neurological disorders, it seems like a logical conclusion — but we need a reference which advances this claim, or otherwise, it seems like original research or downright alarmism. I think that the same holds true here. -Severa (!!!) 02:39, 23 August 2006 (UTC)

While I agree, perhaps something should be said in sounding a cautionary note. I like Cindery's one line suggestion "no long-term studies have been performed to determine the carcinogenicity of mifepristone." Though it should not be bolded nor italics. I'm thinking along these lines primarily because of prosilac; I use this as an example of what we don't know, can hurt us in the long run. - RoyBoy ⁸⁰⁰ 06:49, 23 August 2006 (UTC)

i think i already conceded the point a while back that it should be left at"no studies have been performed..." and that the qualifying info "there may be some concern" was meant to distinguish that "carcinogenicity" left unqualified implies that the risk is equal for all kinds of cancers, whereas synthetic hormones are more associated with breast cancer risk, than say, lung cancer. (the oxford study on the pill, which states "dose and type of hormone not significant when recency of use (10 years) was taken into account", and the recent hrt studies which note that estrogen + progestin together increases breast cancer risk more than estrogen alone" (And recent update that estrogen + testosterone is worse than either). using synthetic hormones is associated with increased breast cancer risk. i think it's less accurate to leave it unqualified, but it just may take up too much room/put an overemphasis on possible breast cancer risk to explain why (but it can be explained by citing medical studies. mifepristone has not been evaluated--but it falls into categories that have: 19 nor, synthetic hormone.)

i also think people think that if something has been approved by the FDA that is was tested for carcinogenicity. (the old 7 year/10 year animal studies aren't even done anymore). they don't think that 30 years from now the WHO or the WHI is going to do a worldwide epidemiological analysis that will be the first long-term study on mifepristone and cancer. and that they might say, hey you people who were the guinea pigs for the cancer risk of this drug, guess what--you should've thought twice. i think it's a very salient fact that no long term studies on animals were done, and that the first generations of people who take this drug should know they are taking the risk, and should be taking it willingly, with informed consent. that they should explicitly know they have no assurance that it's not carcinogenic, and be fine with that. Cindery 00:19, 24 August 2006 (UTC)

I was thinking of removing the entire abortion-breast cancer paragraph and replacing it with just that sentence. Although I find the dominance stuff interesting; it would be good if a source stated that. - RoyBoy ⁸⁰⁰ 02:00, 24 August 2006 (UTC)

Please keep discussion topical. Avoid personal commentary. Wikipedia is not a discussion forum. -Severa (!!!) 05:13, 24 August 2006 (UTC)

long term carcinogenicity studies

re "long term studies are done in animals"

are done in both humans and animals (WHO study on birth control pill/breast cancer is example of long term human study) it's true they don't put humans in lab cages and feed them high doses of a drug for 7 years, but they do do large epidemiological studies to analyze. for mifepristone, long term animal studies were not done/the drug hasn't been in use long enough with enough people to meaningfully assess risk--so, neither is be the answer. perhaps it should be noted in both sections, although i'm in favor of moving animal/in vitro studies down, and teratogencity for both down. per terato, i don't think we need the full gory details, but i do think some note of the risk that if the pregnancy is continued there is risk of birth defects could be mentioned. Cindery 00:58, 24 August 2006 (UTC)

You are incorrect.

The "Carcinogenesis, Mutagenesis, Impairment of Fertility" subsection of the "Precautions" section that is required by the FDA in the full prescribing information part of an approved label refers to in vitro and animal studies, not human studies. The FDA's new format full prescribing information will make this clearer when it moves the "Carcinogenesis, Mutagenesis, Impairment of Fertility" subsection from the "Precautions" section to a new "Nonclinical Toxicology" section (nonclinical = nonhuman).

"No long-term studies to evaluate the carcinogenic potential of mifepristone have not been performed" means that long-term (usually 2 year) carcinogenicity studies in animals (usually rodent species such as the rat or the mouse) were not required by the FDA and were not performed. The FDA and international guideline ICH S1A The Need for Long-term Rodent Carcinogenicty Studies of Pharmaceuticals says: "Carcinogenicity studies should be performed for any pharmaceutical whose expected clinical use is continuous for at least 6 months. Pharmaceuticals administered infrequently or for short duration of exposure do not need carcinogenicity studies unless there is cause for concern."

In cases where long-term studies animal studies of carcinogenic potential were not required by the FDA and were not performed, FDA regulations still require the "Carcinogenesis, Mutagenesis, Impairment of Fertility" subsection to note that long-term studies in animals were not performed. This does not imply there is a "cause for concern" about carcinogenicity--it implies the opposite--that the FDA did not think that there was a "cause for concern" about carcinogenicity at the time it approved the pharmaceutical.

If a pharmaceutical is found in pre-approval clinical trials, in post-approval surveillance of adverse events, or in post-approval epidemiological studies to increase a cancer risk, the FDA either updates the "Warnings" or "Precautions" sections of its full prescribing information or orders it be withdrawn, depending on the nature of the risk.

Citing statements out of context from the Mifeprex full prescribing information to imply there is cause for concern about the carcinogenicity of Mifeprex is Synthesis of published material serving to advance a position and violates the No original research offical policy of Wikipedia.

If there are reliable published sources representing a scientific consensus that there is cause for concern about the carcinogenicity of Mifeprex, please cite them.

69.208.213.220 22:33, 25 August 2006 (UTC)

that doesn't change the fact that the drug has not been in use long enough to assess the cancer risk in humans, and no animal studies means no animal studies. no conclusions are drawn/statement isn't taken out of context--it's all by itself, in the verbatim wording of the product insert. some people don't want to be guinea pigs, some people volunteer--the same piece of information can elicit opposite opinions. the point is that no studies doesn't equal proof of non-carcinogenicity. (and knowing that is part of informed consent).

i would not object to the inclusion of the short term drug=automatic no animal carcinogenicity studies=therefore no cause for concern, but i do think it opens up a larger discussion of what studies the fda approved/required (and the controversies/criticisms therein, for this drug--esp. re the FDA report of the french trials-- and the current state of the FDA).

there is about zero study on carcinogenicity of mifepristone (but klein et al note that one study suggests it may be cytotoxic). it is in no way specific to mifepristone, but the "scientific consensus" of drug companies is to fund research to develop drugs. since they now give the WHO more money than it receives from its 192 member nations in dues, and fund more academic research than anyone else, not much research is being done on causes of cancer in comparison to research on drugs that might be very profitable to treat it. Cindery 23:25, 25 August 2006 (UTC)

If you cannot cite a reliable source that says there is cause for concern about the carcinogenicty of mifepristone, an encyclopedia article on mifepristone should not imply there is.

"Editors must not, however, create arguments themselves in favor of, or against, any particular theory or position."[9]

I have not read the 21-year-old article by Bardon et al[10] cited in the 15-year-old anti-RU-486 book by Klein et al,[11] but the abstract of the article seems at odds with her intrepretation of it--and cytotoxicity (to breast cancer cells) is not carcinogenicity.

68.253.189.24 05:17, 26 August 2006 (UTC)

i think you're missing the point that while it is my opinion that it's a cause for concern, that's not stated in the article viz no long term studies--there's just the required disclosure from the product insert, with no one's opinion. there's no interpretation. it couldn't be more flatly, neutrally stated. those are not my words. i "plagiarized" them :-)

maybe you will find this interesting re cytoxicity:[12] i think cytotoxicity is sort of a fascinating subject viz cancer, since it addresses how something that is carcinogenic can also be anticarcinogenic, depending on a multitude of factors. (why does ionizing radiation cause cancer, but chemotherapy work to treat it; why does tamoxifen block the estrogen receptor at first but then feed it and cause more aggressive tumors sometimes...why is soy maybe preventive before cancer, but maybe proliferative to tumors once they exist? anything cytotoxic can work both ways...and should probably be fully studied. especially if it's synthetic hormone.)

I think you are missing the point. Selectively quoting a statement out of context (no long-term carcinogenicity studies in animals were performed) without explaining why they were not performed (because Mifeprex is not used on a continuous basis and there was no cause for concern about its carcinogenicity) is misleading and not neutral, whether or not the words are your own.

If no reliable source you can cite says there is cause for concern about the carcinogenicity of Mifeprex, what is the point of including discussion of it in an encyclopedia article about Mifeprex besides advancing your own unsupported opinion that it is a cause for concern?

68.253.189.24 06:30, 26 August 2006 (UTC)

the context it is in, in very small print, is a lot of info about medical conditions. couldn't be more neutral/deemphasized. i'm sorry it bothers you that the possibility exists for different people to form different opinions after reading the same material.

"In reality, alkylating and other DNA-damaging drugs, radiation, hormones and antihormones are all carcinogenic." (from cytotoxicity article above). Cindery 08:32, 26 August 2006 (UTC)

poisson ditribution

mkay, this is from first search for source which quotes 1 in 100,000, to find underlying data:

From Medscape General Medicine™ Contemporary Issues in Ob/Gyn & Women's Health Mifepristone-Misoprostol Medical Abortion Mortality Posted 04/27/2006 Mitchell Creinin, MD; Paul Blumenthal, MD, MPH; Lee Shulman, MD

this source cites footnote #9 as the source for the statistic:[13]

that's david grimes md, a familiar name to anyone who reads up on contraception/abortion.

grimes actually calculated it at .8

he calculated .8 by using 1) number of fatalities noted in US by FDA--at time of his editorial, that number was 3. 2) the number of units sold by danco, in a personal conversation to them on novemeber 18, 2004--at the time, 360,000. he states that the number .8 has a 95% confidence interval 0.2-2.4 by Poisson distribution.

i am not a statitician, so frankly definition of poisson distribution may as well be written in ugaratic to me, and 6/460,000 may well be 1 in 100,000, by this means of calculating for all i know.

i would say that this is precedent for using the FDA fatality count and the danco report of units sold to calculate the fatality rate. (but i still would not object to qualifying those numbers as american, or to some of the other qualifications/contexts we have discussed.)

note also grimes extremely prochoice/pro-mifepristone/indicating, that using FDA/danco numbers, if any indication of bias, is bias favorable to mife. (such as no questioning of danco's numbers=procedures, etc.) Cindery 02:52, 24 August 2006 (UTC)

Thanks for doing the research, however nothing you have said changes wikipedia policy. I want to be crystal clear on this. We cannot publish a mortality rate for the first time on wikipedia. You even claimed that you weren't a statitician, but even if you were, you'd need to have a reliable source publish your calculations first before we could cite them here. This is policy and I don't see how it can be argued. I felt my compromise was just fine. It gave both figures from both sources, without doing original research of claiming those numbers represent a mortality rate. If we keep the numbers seperate and do not claim they represent a mortality rate, I think its fine. Saying "There have been 6 reported deaths" and "Danco states it shipped 460,000 units" is fine. Saying "The mortality rate is 6 in 460,000" is not. Do you see the difference between the two? The only thing I am objecting to above is your suggestion to "calculate the fatality rate" ourselves. That isn't our jobs as editors. We simply report on our sources, not synthesize, comment on, or interpret our sources.--Andrew c 17:28, 24 August 2006 (UTC)

again, i think it would be very interesting to see the result of an accuracy dispute mediation re whether arithmetic is OR. (poisson distribution with a confidence interval gives a margin of error of about two points, i think. recommending a statistical method--one among many--like that was attempt at diplomacy.) careful not to appoint yourself the sole arbiter of wikipedia policy, and insist that you are in a position to make it "crystal clear" or be "strict" about it to someone who has reasonable grounds to disagree with you--doesn't come off sounding collaborative.

re "we do not comment on synthesize, or interpret our sources" it would be very nice to see you making an effort to observe that to improve the quality and neutrality of the article. (for example, you had no criticism of the original comparisons or their rhetorical construction, or the inaccuracy of the surgical abortion mortality rate. you had no objections to the straw man constructions, and resisted edits to them.)

this is in print, from the subcommittee hearing "RU-486: demonstrating a low standard for women's health?" (but it suggests attribution of ectopic--indicating a difference of opinion about that, which should perhaps be noted in the article.)

[2] The mortality rate for women who procure a surgical abortion is 0.1 in 100,000 during the first eight weeks of pregnancy, the period for which RU-486 is available for women. Dr. Michael Green, based on usage rates of 460,000 and 4 deaths, suggested that the risk of death from chemical abortion is ten times greater. See, Michael F. Green, M.D., Fatal Infections Associated with Mifepristone-Induced Abortion, Dec. 1, 2005, N. Engl. J. Med 353;22 at 2318. Current numbers suggest, however, eight deaths in the United States, while, according to the manufacturer, 575,000 women have used the drug. This works out to 1 in about 71,875, or 1.39 for every 100,000, suggesting a Mifeprex fatality rate that is fourteen times greater than that with surgical abortion during the eight weeks of pregnancy. Cindery 19:00, 24 August 2006 (UTC)

Ok, I'm going to ignore your off topic comments on my editing behavior and just say, thanks for finding a source for your claim. Well, the source doesn't exactly say your claim "6 in 460,000". It says 8 in 575,000. But still, now we have a source. That's all I was asking for. Thanks.--Andrew c 20:16, 24 August 2006 (UTC)

we never needed a source to add 1+1=2; arithmetic is not original research. Cindery 23:04, 24 August 2006 (UTC)

Ovariectomized female rats were treated with oestradiol and the progesterone-antagonist mifepristone.

I'm a little concerned over the following:

A 1992 study of female rats treated with mifepristone found that they developed lethal bacterial infections following copulation.[14]

This is inserted at the end of a paragraph about the mifepristone deaths. This is part of the problem with using primary sources so extensively. Maybe this information is relevent, but it would take a trained professional to figure it out. Wikipedia is not an encyclopedia written by trained professionals, but instead written by the people (which is why there are strict limitations on verifiability and original research). Reading the abstract, this 1992 study dealt with "[o]variectomized female rats [being] treated with oestradiol and ... mifepristone." Something having to do with "copulatory plugs" (here is a page that explains what they are) causing infection only in the rats treated with oestradiol and mifepristone, but not the ones with oestradiol alone. Also the abstract says specifically "occasionally with lethal consequences", while our text is more vague about the frequency of the lethal infections. Anyway, putting this at the end of the paragraph seems to suggest that doctors knew 14 years ago that mifepristone caused bacterial infection, but we'd need a source to make this claim. I question how notable this one study is, and how relevent it is in this paragraph. Regardless, the wording is misleading. If we are to keep it in, I'd suggest moving it to the animal studies section, and rephrasing it "A 1992 study of ovariectomized female rats treated with mifepristone found that they developed bacterial infections which were occassionally lethal following copulation and possible problems stemming from copulatory plug passage". However, if we have a source that states that this study is relevent to the discussion of human patient deaths, then lets cite it.--Andrew c 22:11, 24 August 2006 (UTC)

there was a quote--i think from the boston globe article (15), something like "scientists have been warning for years that mifepristone could cause massive bacterial infections." but it didn't cite any reference. i searched pretty exhaustively, but i only found that one study. it could be rewritten so that quote is followed by the study, but i think it's a pretty outrageous quote, so i didn't include it. (i.e., even if it appears balanced by a single animal study, it still sounds alarmist, i think.) the it's immunopressive/it wouldn't cause infections of only one organism--i set that up to include two points of view--but that didn't seem as though it would work out the same for boston globe quote + animal study. nevertheless, the animal infection study does sort of hang there, because i left out the boston globe quote. i still think it's useful/interesting/relevant info. in editing the fatalities section, i was trying to focus on all the opinions of how it could have happened from all medical points of view. i don't think the rat study lends itself to any conclusions.

re pubmed--i guess because i have edited mostly medical articles, i do not share your point of view. neither do other people on medical articles--medical studies are always included in medical articles (all the ones i know) and the actual study is preferred to interpretations of it. mifepristone is naturally a hybrid of sources, because it's medical *and* social/political. but an attitude of "i think this is a social political issue" doesn't mean there are people who think it's more of a medical issue. i think you're just going to have to live with a healthy multiplicity of sources. Cindery 22:52, 24 August 2006 (UTC)

I understand completely that medical articles are going to be a bit heavier on the journal articles and primary sources. I was just pointing out that this is an example of how citing primary sources can be problematic. However, I just want to be clear that I am not anti-primary sources, and I understand that this article isn't just a social/polical thing. What I am saying, it is perfectly fine to report the conclusions of primary sources. However, the issue is, we shouldn't be interpreting these conclusions for the first time here. I just found the placement of this study at the end of the paragraph a little weird, and the wording a little off. If after all these bacerial infection deaths in humans, no one in the media or medical journals is citing this rat study, it makes me wonder if there is a reason (because I am not a medical expert, maybe there is something I am missing that obviously makes this study not relevent. or maybe we are just ahead of everyone else, and therefore would be publishing original research that this rat study relates to the human deaths). You understand my concern? I'm not exactly sure what we can do, and I don't want to sound like a broken record, but having sources (primary or not) making this connection is always better in my mind. Anyway, what do you think about my proposed rewording of the sentence?--Andrew c 23:08, 24 August 2006 (UTC)

people can draw their own conclusions from primary sources; that's why i think they're better (usually not just far superior to dumbed down interpretations,-- esp. ones in commercial press which are trying to sell something or push a pov--but entirely different things, practically. i think it's' sobering sometimes for people to read for themselves a study upon which a lot of hype was based...) anyhow, i don't think you are the arbiter of whether "it would take a trained professional to figure it out."--it's not even a terribly complicated study. it sort of implies that most people are too stupid to understand a primary source, and everything has to be idiot-proofed by the commericial press for them. i disagree. (especially because of the commerical level of distortion in the mediated interpretations.)

but, that's general, and the specific point here obviously is, should this be contextualized with the boston globe quote?--maybe it should be. there *is* a yawning chasm between that quote and one animal study, so maybe the comparison speaks for itself. i don't know that an overcomplicated summary of the study is necessary--it places undue emphasis on it (and simple summaries of medical studies are provided in "other uses." we know that it may inhibit one cell line of gastric cancer--in order to sufficiently summarize that, do we need to note that the line is MKN-45, in vivo and in vitro? and we know that it may have some therapeutic effect on one cell line of ovarian cancer--to summarize that, do we need to know that it was 3AO, and that it had "an effect on aptosis"?) Cindery 23:46, 24 August 2006 (UTC)

Ectopic Pregnancies and 27 cases

Could you please post a link to the page where the FDA reports this and I'll format the reference? If the reference is already used, we can name the ref tag, and then have the citation point to the existing footnote.--Andrew c 01:43, 25 August 2006 (UTC)

rat study

according to the author of the boston globe article (personal correspondence with her yesterday) the citation for "scientists have been warning for years..." is this:

Comment: pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii Pr. Didier Sicard and Dr. Laurence Chauvelot-Moachon Ann Pharmacother 2005;39:2142-2143. DOI 10.1345/aph.1G189a Published Online, 15 November 2005

i haven't had a chance to read it yet, so i don't know if it references the rat study. she does reference the article above in the text of her article, but i don't think she makes it clear that "scientists have been warning..." and the sicard/chauvelot-moachon editorial comment are directly linked. but, just because i didn't get that is not definitive proof that no one else could it; could be dimness on my part. anyway, definitely personal correspondence with the author is OR :-), but perhaps the sicard/chauvelot-moachon comment could put rat study in better context than boston globe, bypassing it and possible problemmatics with it re 1) statement pretty strong 2)link between statement and editorial comment by sicard/chaevelot-moachon maybe not so clear. Cindery 16:19, 25 August 2006 (UTC)

ru-486: misconceptions, myths, and morals

the full text of this book--which is out of print--is available online, but the copyright does sepcifically state that it may not be stored in a retrieval system without permission. so it can be cited, but not with a link to online retrieval of the full text, i think--so i have not replaced link after my bungled attempt. Cindery 16:19, 25 August 2006 (UTC)

proposed revision of "usage in australia"

i think the account of political machinations in australia over the approval of mifepristone is fascinating and complicated enough that it bears expansion into its own article, or inclusion in full into another article about australian politics.

but... the account the way it is presented here is very overcomplicated in comparison to the account presented for any other country. since the article is about the drug--though politics should definitely be mentioned/are definitely relevant--i think they should be summarized as they are for US and new zealand, rather than treated in depth.

here is version of a proposed summary (which would hopefully have a wikilink to complete text at another article):

Mifepristone was banned in Australia in 1996. In late 2005, a Private Member's bill was introduced to the Australian Senate to lift the ban and transfer the power of approval to the Therapeutic Goods Administration. The move caused much debate in the Australian media and amongst politicians. The Bill passed the Senate on 10 February 2006, and mifepristone is now available in Australia. Cindery 02:37, 8 September 2006 (UTC)

here is the long version, preserved for other editors--if anyone wants convenient access to make changes/start new article etc. Cindery 17:59, 14 September 2006 (UTC)

Mifepristone was effectively banned in Australia in 1996 in a compromise by the Howard Government with conservative Independent Senator for Tasmania Brian Harradine to amend the law to require ministerial approval of RU 486 in exchange for his support for the partial sale of the then fully state-owned telecom company Telstra.

In late 2005, a Private Member's Bill co-sponsored by Lyn Allison, Fiona Nash, Claire Moore and Judith Troeth was introduced to the Australian Senate to remove this statutory provision and transfer the power of approval to the Therapeutic Goods Administration. The move caused much debate in the Australian media and amongst politicians. The Bill attracted public support from the Democrats, Australian Greens and several individual members of the Labor, Liberal and National parties. Neither the Labor Opposition nor the Coalition parties took a party stand in favour or in opposition of the Bill and allowed for a conscience vote. The Family First Party and Coalition Senators Barnaby Joyce, Bill Heffernan and Ron Boswell signalled their strong opposition. The Health Minister Tony Abbott, a pro-lifer, was targeted by supporters of the Bill.

The Bill passed the Australian Senate on 10 February 2006, causing Minister Abbott to label it a no confidence vote in him and the Government. The Prime Minister disagreed, and indicated that the Senate vote was not a vote of no-confidence in Minister Abbott or government ministers. The Australian House of Representatives has considered the bill, and two amendments proposed during the debate, rejecting the both of them, and passing the bill unamended. The bill will award final-say on the drug's use to the TGA. If approved by the TGA, the availability of the drug may be assisted with listing on the Pharmaceutical Benefits Scheme.

newspaper link

i'm going to move this out of external links into the controversy section as a ref for "pro-life actively campaigned.." so it's not the only external link which is a news cite, and to support the statement in the article. but will leave here in case there are objections. Cindery 19:37, 15 September 2006 (UTC)

• "Abortion Foes To Boycott Drugs (Altace) Made By RU-486 Manufacturer." The Virginia-Pilot. Associated Press. July 8, 1994.

result of "request for feedback"

i think all of yomangani's criticisms are good advice and will start fixing/report is archived here if anyone else wants to make changes as well. Cindery 00:02, 16 September 2006 (UTC)

Mifepristone

...I hate to be a "feedback hog,":-) but you gave such good advice I wanted to ask about this one too. (I put a lot of work into it, but so did other editors; I didn't start it.) It still needs some refs in the history section I think, and the "Use outside United States" should be expanded, I know...but how does it read overall for general reader, do you think? Does it have too many technical/medical terms? Should the product insert not be quoted verbatim in small type? Is it missing anything/NPOV enough? Does it go into too much detail about the fatalities? All criticism about how to improve it wanted and welcome. Thanks in advance, Cindery 03:58, 15 September 2006 (UTC)

• Quite comprehensive but there are few problems:

• It is US-centric - FDA is not linked or explained; nearly all the statistics and data are US information; in the lead it is said it was initially available in France, but this is not mentioned again until late in the article - the history section should come before controversy to help balance this out.
• I would put "Other possible uses" before controversy as well - since the controversy section is such a large part of the article it looks biased to have it so close to the beginning of the article.
• The lead states "it is useful in humans an abortifacient...", this should be rephrased with a more neutral tone ("its uses are...") as "useful" suggests a POV.
• Its uses for the treatment of endocrine conditions receives little further coverage after the lead.
• Citation styles are mixed with footnotes and external links right next to each other
• There are incidences of "US" and "U.S." right next to each other, and 60-mg,200mg and 200 mg (the manual of style recommends value then a space then the unit).
• The clinical trials section needs more information: what dosages were the women on, what symptoms were they being treated for, what was the sample size?
• The quoting of the packaging label is awkward after the contraindications have been listed above (and the quotes aren't closed anyway) - I'd list this information in the same way you handled the information above it.
• There are a lot of medical opinions on its immunosuppressant effects and not many for the opposing view, but the section isn't badly balanced considering, and that may just be all the information there is available.
• The "History" and "Politics and use outside the United States" sections are confused. History should probably only cover the point up to launch.
• It needs more references as it is an emotive subject that is liable to be challenged if references are not provided (and probably even then).
• Further wikilinking of some medical terms would be beneficial if the articles exist. Yomanganitalk 22:59, 15 September 2006 (UTC)

pdf ref for approval dates by country

[www.huksam.hacettepe.edu.tr/ingilizce/ ilgiliyayinlar/pdf/International_Experience_Mifepristone.pdf}

"mifepristone abortions take between 3 and 30 days"

Is there a source for this? I feel it needs to be explained a little further at the very least.--Andrew c 22:53, 11 November 2006 (UTC)

it's from the article--2nd pill is taken two days later; longest reported bleeding was 30 days. we could put an average--also from the article--instead of a day range: "Surgical takes ten minutes, mifepristone averages 3-7 days" or something. the refs already in article could be recited in this new section (I didn't create new section; I don't know who created it or why, or why no refs are cited. It didn't seem like a terrible idea, though, so I fixed it instead of deleting it or moving it to talk.)

Cindery 03:34, 12 November 2006 (UTC)

Well the issue I was concerned about was actual procedure vs. recovery time. Mifepristone averages about 2-10 hours of severe cramping. But recovery or bleeding may continue for up to a month (14 days is typical?) but for a surgical abortion, the actual procedure take 5-15 minutes, but again recovery may take 6 weeks before all bleeding stops (typically a lot less). So I just thought it was misleading to to say surgical abortion takes 10 minutes and you are done, while chemical abortion could take 30 days, when in actuality, surgical abortion is a lot short, less crapming, less side effects, and is generally recommended by clinics, it still have a comparitavely long recovery time as chemical abortion, right?--Andrew c 19:40, 13 November 2006 (UTC)

...the "recovery time" and "the procedure" aren't as easily separated for mife, because the heavy bleeding/expulsion of products of conception are the abortion; whereas post-procedure bleeding for surgical abortion is just "recovery time" and is spotting/there's also the two pills over three days problem. Cindery 20:21, 13 November 2006 (UTC)

Structure error.

In the picture that shows the structure, there is a hydrogen missing from the hydroxy group. I would edit this myself, but I have neither the time nor the experience with wikis.

128.175.87.38 01:56, 15 November 2006 (UTC)

Corlux

I've removed the sentence stating that Corlux (mifepristone) was no more effective than placebo in a Phase III trial for psychotic depression. I can't access the newspaper article which was cited as a source, but I did look on PubMed. The only published Phase III trials I found were these: PMID 16889757 and PMID 16160710. The former was e-published in August, around the time of the inaccessible newspaper article - perhaps this was the "failed" Phase III trial the paper referred to? But both studies report improvements in measures of psychosis with mifepristone. There's also a letter to the editor (PMID 17109015) in response to the first of the two PubMed citations I've mentioned, alleging that the statistical methods and clinical relevance used were questionable. Nonetheless, the only peer-reviewed Phase III data I can find report that mifepristone is effective, although one could wonder about the clinical relevance of the endpoints and study design. Hence, in accordance with WP:RS, "avoid citing the popular press on scientific matters", etc I removed the Corlux sentence and added the PubMed refs to the lead sentence in the section. MastCell 19:40, 19 December 2006 (UTC)