Tuesday, August 17, 2010

ellaOne: Matthew Perrone and The AP Should Be Ashamed of Themselves


First, go wrap your head in a couple of towels. Then, and only then, go read this AP article on ellaOne and do your best to keep the head-hitting-desk at a minimum.

How is it possible for what should be a simple article about the approval of the new emergency contraceptive pill (ECP) ellaOne to contain such a massive amount of misinformation? Words fail me. Fortunately, my fingers still work so here we go:

Get everything wrong from the start

WASHINGTON – Federal health officials on Friday approved a new type of morning-after contraceptive that works longer than the current leading drug on the market.

The pill ella from HRA Pharma reduces the chance of pregnancy up to five days after sex. Plan B, the most widely used emergency contraceptive pill, begins losing its ability to prevent pregnancy within three days of sex.

Two paragraphs in and everything is wrong. (Is this some kind of record?)

First, Plan B is not the current leading ECP drug on the market seeing how, you know, it's been withdrawn and replaced with Plan B One-Step for quite some time now.

Second, the terminology morning-after contraceptive is wrong, wrong, wrong. It's either post-coital contraceptive (the class), or the ECP (a group in the class). You can use "morning-after" pill only if you make it clear it's an incorrect common usage. Otherwise you risk confusing your readers with the implication that the morning-after time period has any particular significance for the ECP dosage regimen. Which, of course, it doesn't.

You take the ECP as soon as possible after the act of unprotected intercourse -- an hour, 12 hours, two days, etc., up to five days.

Third, ellaOne, and pay attention AP reporters because this is important, as well as all the other available ECPs -- Plan B One-Step, Next Choice, iPill / Nextime, Levonelle One Step -- reduce the chance of pregnancy up to five days after sex.

But wait, there's more! All ECP brands, past and present, including Plan B and ellaOne begin losing their ability to prevent pregnancy the longer you wait to take them. For example, take ellaOne within 0 to 72 hrs after unprotected intercourse and it's 85% effective (pdf). Take it between 48 and 120 hrs (5 days) and it's only 61% effective.

Read the offending paragraph again:

The pill ella from HRA Pharma reduces the chance of pregnancy up to five days after sex. Plan B, the most widely used emergency contraceptive pill, begins losing its ability to prevent pregnancy within three days of sex.

To imply that one brand of ECP is more effective than another when you don't have the evidence for that is bad enough (more on that in a bit). To then mislead your readers about the effectiveness of ECP over time is inexcusable.

The effectiveness of ECPs is time-dependent; the sooner you take the pill, the better it works. This is crucial information about ECP regimens and failure to communicate it clearly and correctly can lull people into a false sense of security causing them to use ECPs incorrectly.

Get the studies wrong

The Food and Drug Administration approved the drug Friday as a prescription-only birth control option. The ruling clears the way for U.S. sales of the drug, which is already approved in Europe.

Morristown, N.J.-based Watson Pharmaceuticals will market the drug in the U.S. under an agreement with HRA. Watson said it will launch the pill in the fourth quarter.

Studies of ella by its manufacturer showed the drug prevented pregnancies longer and more consistently than Plan B.

In a head-to-head trial between the two drugs, women who took ella had a 1.8 percent chance of becoming pregnant, while women who took Plan B had a 2.6 percent chance. Experts tracked nearly 1,700 women who randomly received one of the two pills within three to five days of having unprotected sex.

More paragraphs, more major mistakes.

First, the trial did not compare ellaOne to Plan B. Rather, ellaOne was compared with NotPlan B.

Second, the Lancet study did not show that ellaOne prevents pregnancies longer and more consistently than Plan B NotPlan B. All it did show was that ellaOne is no worse than NotPlan B. As I mentioned in the linked post:

This may seem like a distinction without a difference, but it's not.

It's quite likely that ellaOne is more effective than the levonorgestrel brands when taken 3 to 5 days after unprotected intercourse but that hasn't been established yet and you should know that when deciding if ellaOne is the best emergency contraceptive option for you.

Sure, we all wish ellaOne turns out to be a better drug than the available alternatives. But until the evidence is in it is highly irresponsible to mislead your readers about the drug's effectiveness over time.

Be unclear on what's in ellaOne

Plan B is made by Teva Pharmaceuticals and is also marketed in several generic versions. Unlike ella, Plan B and other generic versions are available without a prescription for women 17 years and older.

HRA Pharma did not request over-the-counter status for its drug.

Ella uses the hormone progesterone to delay ovulation, a key step in the fertilization process.

Quick, when you read Ella uses the hormone progesterone to delay ovulation, what do you understand that to mean, A or B:

A) ellaOne contains progesterone and uses it to delay ovulation?

B) ellaOne contains ulipristal acetate (UA), a second generation progesterone receptor modulator (PRM), basically a progesterone antagonist. So, by blocking progesterone's action and modifying its activity ellaOne uses progesterone to delay ovulation? 

I would really like to believe that Matthew Perrone knows that ellaOne contains UA and he's just not very good at conveying that information but I doubt it. And here's why (emphasis mine):

Ella uses the hormone progesterone to delay ovulation, a key step in the fertilization process.

Despite this, the drug has drawn criticism from...groups who say it is closer to [another] pill....

Groups...argue the drug is chemically similar to the...drug mifeprestone....

I've truncated the paragraphs because I don't want you to get distracted by all the other misinformation that needs to be corrected. I'll do that in a moment. For now just focus on whether Matthew Perrone knows that ellaOne contains UA or not.

So, according to Perrone, despite the fact that Ella uses the hormone progesterone groups argue that ellaOne is chemically similar to mifepristone. [Incidentally, notice the caliber of reporting here. Who cares what the drug's actual composition is? Perrone reports on all the competing arguments from assorted groups and then you get to decide. "Professional" reporting at its best!]

Since both UA and mifepristone are PRMs, it looks to me that Perrone has no clue that ellaOne contains UA. In which case, both Perrone and the AP should be very ashamed for unleashing this level of misinformation on their readers.

Moving on.

When ignorance isn't enough, it's propaganda to the rescue

Despite this, the drug has drawn criticism from anti-abortion groups who say it is closer to an abortion pill than an emergency contraception pill.

Groups including the Family Research Council argue the drug is chemically similar to the abortion drug mifeprestone, which can be taken to end a pregnancy up to 50 days into the gestation period. That drug has been associated with severe infections and bleeding after abortion. However, FDA reviewers reported no life-threatening medical side effects with ella.

Incorrect information on top of incorrect information.

Before I go on, a quick note about the brand names. Notice the use of ellaOne and mifepristone in the paragraph above. That is incorrect. You don't mix brand names and compound names. So, the correct way is either ellaOne and Mifeprex (brand names) or ulipristal acetate (UA) (ellaOne) and mifepristone (Mifeprex). Moving on.

First, if you hope to maintain any credibility as a journalist you don't allow groups like the Family Research Council to use you as their propaganda mule.

"ellaOne and mifepristone are chemically similar so, um, OMG...abortion!!!Eleventyone!!111" has no place in a fact-based article.

Both ellaOne and Mifeprex are PRMs. Neither is a magic pill, nor, for that matter, an abortion pill. Depending on dosage and regimen, PRMs have different mechanisms of action. In particular, mifepristone can work on ovulation to prevent pregnancy (birth control) or the uterus to terminate a pregnancy (abortifacient). The specific doses/regimens are not interchangeable. The fact that mifepristone is a PRM and the fact that it can be part of a regimen which can be taken to end a pregnancy up to 50 days are totally irrelevant to emergency contraception and ellaOne.

As to ellaOne, it is a second generation, selective PRM, the first molecule to have been specifically designed and developed for use as an oral emergency contraceptive. (pdf)

Second, "mifepristone is Satan's drug but don't worry nobody's dropped dead yet from ellaOne" also not appropriate for a reality-based article.

In general, the side effects associated with an abortifacient regimen that contains mifepristone (or any other drugs for that matter) are totally irrelevant to an UA emergency contraceptive regimen. That's because, once a pregnancy is established, the anatomy and physiology change. For example, the delayed or prolonged bleeding/spotting caused by manipulating hormones with ECPs is not comparable with, say, the bleeding some women may experience after a termination, or even a term delivery, from retained POCs.

In particular, mifepristone has not been associated with severe infections after abortion. I know I just mentioned that mifepristone's side effects are irrelevant, but this "associated with severe infections" myth needs to die already so let me spend just a moment debunking it.

Briefly, there have been no severe infection cases in patients using the FDA-approved regimen of 600 mg mifepristone po, followed by 400 mcg of misoprostol po. There have been several fatal infection cases in patients using the off-label regimen of 200 mg mifepristone po, followed by 800 mcg of misoprostol PV. No association has been found between mifepristone and misoprostol, regardless of regimen, and the severe infection cases. (More on this here, here, and here.)

Back to the ellaOne/mifepristone paragraph, the best thing to do is to ignore it altogether. There's just too much misinformation, and the spectacle of a reporter being taken for a ride is unseemly. Which brings me to the bottom line on this entire article.

The AP throws a mishmash of confusing, incorrect, and irrelevant information at you and expects you to, somehow, make sense of it all, from extracting what few factual bits there are to identifying and ignoring the misinformation.

What kind of bizarro reporting is this?

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At 7:20 AM, Anonymous Anonymous said...

Thank goodness someone has taken the time to properly evaluate the nonsense in the press about UA.
Well done

At 2:06 PM, OpenID Rachel said...

Nice. Every time I see "morning after" in one of these stories, I cringe. It might be worth noting, though, that while the other drugs are thought to work up to 5 days (and I think there are some studies demonstrating some efficacy, but would have to look them up), they're not explicitly *approved* for that time frame, so they can't be marketed that way. Last I checked, I believe, could be wrong about that.

At 3:30 PM, Blogger ema said...


Thank you. I did try to contact the reporter to ask him to issue a correction but no luck, so far.


Very good point. I'm so used to going by clinical guidelines I didn't even think to mention it.

The LNG ECPs are only FDA-approved for 72 hrs, but should be taken up to 120 hrs*, while ella is FDA-approved for 120 hrs.

*The initial studies included only women who used the regimens within 72 hours after intercourse.32,42 Consequently, some product package instructions, including that for Plan B One‐Step and Next Choice, and older guidelines advise use only within that time frame. However, more recent studies indicate that the regimens continue to be moderately effective if started between 72 and 120 hours.9,11,40,41

At 12:21 AM, Anonymous Anonymous said...

And another thing that is utterly incongruent.... So we have some misinformation about this molecule... But this molecule is also being researched for fibroids... and if its successful isn't it going to save women from uneedy hysterectomies? Unhealthy bleeding, pain, lack of confidence etc... isn't that a good thing??? And surely... somewhere along the line that will help create life???
Own goal to these misinformed protestors....

At 9:53 PM, Anonymous Anonymous said...

Ellaone has not worked for me!!! I took this morning after pill 27hrs after having unprotected sex, now I have found out that I am pregnant and I now have to face a completely uneccesary and distressing abortion.... this drug has failed me and because of this I am now left with no choice but to end a human life that should have been prevented! THANKS ELLAONE FOR RUINING MY LIFE!!!!

At 11:58 AM, Blogger ema said...

Anon @ 9:53 PM,

It is unfortunate that Ella did not work for you but not unexpected. It's important to keep in mind that Ella is not a miracle drug, one that's 100% effective, but rather a second-best alternative to using a regular method of birth control to prevent pregnancy.

For the future, especially in light of your belief that abortion "end[s] a human life" you should strongly consider using a regular method of birth control consistently. And, just as an observation based on information gleaned from an anonymous comment, perhaps your decision to terminate the pregnancy needs some more consideration.


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