Adiana Sterilization System

Adiana

Adiana, a new transcervical sterilization system, is performing well in phase III studies:

Adiana in situ

Photos via Ob.Gyn. News

The Adiana transcervical sterilization system appears to be easy to use, safe, and effective, according to phase III data, Alan Johns, M.D., reported at the annual meeting of the AAGL.

The Adiana Complete system is available only for experimental use, but U.S. Food and Drug Administration submission is anticipated in mid-2006, said Dr. Johns, one of the clinical investigators in the trial.

The FDA approved Essure, currently the only nonincisional approach to female sterilization, in November 2002. The Adiana system "is the next step in the evolution of hysteroscopic devices," Dr. Johns said in an interview. It may be better than the Essure simply because it doesn't require as much manipulation and the whole device is altogether shorter and easier to put in and cannulate, he said. "More importantly, in contrast to the Essure system, after the Adiana matrix has been deployed, nothing remains in the endometrial cavity."

This may be important in women who later choose to undergo in vitro fertilization or endometrial ablation, because these options can be limited by the presence of a portion of a device in the endometrial cavity, he said.

The Adiana system also differs from Essure in that it uses radio frequency energy before placement of the polymer matrix in the fallopian tubes. This process is designed to stimulate vascularized tissue ingrowth into the matrix material, said Dr. Johns of Fort Worth, Tex. He accepted payment to enroll and treat patients in the trial but said he has no financial interest in Adiana Inc.

As of Sept. 30, 2005, the Evaluation of the Adiana System for Transcervical Sterilization Using Electrothermal Energy in Women (EASE) study had enrolled 770 women at 16 sites. Almost half (47%) were aged 28‚–33 years. A total of 655 patients were taken for hysteroscopy, and 10 were excluded for hysteroscopic findings. The remaining 115 patients either withdrew from the study or were excluded from the study protocol.

Treatment was attempted in 645 patients and bilateral placement was achieved in 614 (95%).

This placement rate is comparable with that attained by Essure in its clinical trials, he said. Lateral location of the ostia is the most common reason for failure of placement of hysteroscopic sterilization devices.

The average procedure time from insertion to removal of the hysteroscope was 12 minutes. Local and oral anesthesia was used in 35% of patients, local anesthesia plus intravenous sedation in 48%, and local plus intravenous analgesia in 17%. Nine patients were lost to follow-up or are awaiting 3-month hysterosalpingogram (HSG).

Failure of tubal occlusion occurred in 26 (4.29%) women, and there were two pregnancies. One occurred after proper placement of the device and HSG confirmation of occlusion. The second occurred when a physician misinterpreted the HSG and retreated the patient but placed the device in the occluded tube instead of the patent tube. There were no device-related significant adverse events. One procedure-related incident of hyponatremia was reported. All other events were minor and included spotting, cramping, and headache.

Here is a good review, from 2003, of transcervical birth control methods in the U.S. pipeline.

Update: The Essure site.

Grand Rounds

Don't miss this week's Best of The Year Grand Rounds edition.

Cervical Cancer Screening and HPV Typing

While we're on the subject of cervical cancer, I thought you might find this article--on the human papillomaviruses (HPV) screening standard of care--useful. It's a bit heavy on medspeak, but here are the main points:

[I]n the U.S., in 2005, there will be an estimated 10,370 cases of cervical cancer and about 3710 related deaths.

On a worldwide basis, HPV has been demonstrated to be present in more than 95% of all cervical cancers of all histologic types.

HPV16 accounts for approximately 50% of all invasive cervical cancers and more than 25% of cancer precursors. [For more on HPV go here.]

The conventional Papanicolaou (Pap) smear is the world's most successful cancer screening test.

[M]ore than 50% of the patients in whom cervical cancer develops have never been screened, and another 10% to 20% of those patients have not been screened in at least 5 years.

[A]t least 30% of the patients in whom cervical cancer develops have had a "false negative" Pap smear and approximately half of those false-negative results are due to sampling error while the remaining 50% actually are screening or interpretive errors.

Any single cervical cancer screening event may only be 50% sensitive for prevalent disease. Thus, it is only through the repetitive application of independent screening events, at relatively short intervals, that the Pap smear "system" is really efficacious.

[An aside. There are two types of Pap smear techniques: 1) the older one, or conventional dry-slide Pap (small wooden collection device, and sample is smeared on glass slide), and 2) the newer one, liquid-based Pap, or ThinPrep (small, brush-like collection device, and sample is rinsed in liquid).]

60% of colposcopically derived biopsies read as high-grade cervical intraepithelial neoplasia (CIN) come from patients who have Pap smears read as either ASCUS [Atypical Squamous Cells of Undetermined Significance] or LSIL [Low-Grade Squamous Intraepithelial Lesion].

[I]n patients with cytologically diagnosed LSIL, high-risk HPV testing has little utility. This is because at least 84% of patients with LSIL on cytology are already high-risk HPV positive. Hence, HPV testing will not effectively triage these patients in whom it was established that there is a 25% to 30% likelihood of detecting a high-grade cancer precursor over 2 years.

In contrast, for the ASCUS group,

[The ALTS study] firmly established adjunctive testing for high-risk HPV as the standard of care for the triage of patients with mildly abnormal cervical cytology... [T]he essential finding of the ALTS trial was that HPV triage was 92% sensitive for prevalent CIN3 in the ASC-US group while referring only 53% of patients for colposcopy.

So, if you already have an abnormal Pap test, you should have high-risk HPV testing. But what about doing HPV typing at the same time as the initial Pap test? Would HPV testing at this stage be useful? After all:

Several epidemiologic studies looking at the prevalence of HPV detection vs age demonstrated that there is a significant reduction in HPV prevalence throughout the third decade, such that women in their 30s routinely show prevalence of detectable HPV of 10% or less.

The short answer to our question is that performing both a Pap test and HPV typing for primary screening might be useful (depending on particular patient circumstances), so it is an option that you should be aware of:

The primary data supporting the utility of HPV testing in conjunction with cytology for screening consist of several studies that evaluated more than 40,000 women in a variety of clinical settings. All studies demonstrated that HPV testing was more sensitive than cervical cytology regardless of the clinical setting. The combination of HPV plus cytology achieved sensitivities of over 95% in 6 of 8 studies. At such high levels of sensitivity, many have been concerned that too many patients would be referred to colposcopy, and those referred would fail to have identifiable lesions. The inherent advantage of cytology is that cytologic abnormality tends to have very high specificity, particularly when interpretations are adjudicated. Surprisingly, HPV testing achieved specificities that were comparable to or only slightly less than those with cytology alone. This undoubtedly reflects the problem of interpretive variability inherent in morphologic assessment. The combined test had a specificity of more than 90% in 6 of the 8 studies presented to the US Food and Drug Administration (FDA).These data led to widespread discussion and eventual publication by both The American Cancer Society and The American College of Obstetrics and Gynecology of revised practice guidelines that included the option of HPV testing in conjunction with cytology for the primary screening of patients.

One advantage of primary screening with Pap + HPV typing is that patients who have both a normal Pap smear as well as a negative high-risk HPV test do not need a repeat screening examination for at least 3 years (provided baseline stays constant--e.g., same partner, still in a monogamous relationship, etc).

Last, but not least, here are the guidance recommendations on how to incorporate HPV testing as an adjunct to Pap smear screening:

-- patients with SIL cytology or ASCUS and a positive HPV test result are referred routinely for colposcopy

-- patients who are double negative [normal Pap, no HPV] are recommended to have repeat testing every 3 years

-- patients who have equivocal cytologic abnormalities [ASCUS] but who are HPV negative are recommended to have a repeat examination in 1 year*

-- patients who are high-risk HPV-positive but cytologically normal [~ 3% to 5% of pts; HPV testing detects one of the high-risk HPV types, like HPV16, but the Pap test is normal] should undergo a repeat examination in 6-12 months with both HPV testing as well as cervical cytology*

The rationale for repeat testing, rather than colposcopy referral:

Because it is well established that HPV persistence is the major risk factor for developing cervical neoplasia, several recent studies have shown that patients who are high-risk HPV positive and cytology negative have a risk of developing CIN2+ of approximately 4% to 8% at 12 months. This scheme of repeat testing is nearly 100% effective at identifying all patients who have high-grade disease. Conversely, approximately 40% to 60% of patients initially identified as being HPV positive and cytology negative will clear their HPV infection over this short follow-up.

[*I would strongly urge you to discuss this recommendation with your Ob/Gyn in detail. While for some selected patients this guideline might be applicable, for others, waiting for up to one year to follow-up is simply too long.]

The Pill Doesn't Affect Cervical Pre-cancer Risk

Interesting news about the risk of developing CIN, use of hormonal birth control, like the Pill, and the number of pregnancies and children:

NEW YORK (Reuters Health) - Women with certain types of human papilloma virus (HPV) infection run the risk of developing CIN -- cervical intraepithelial neoplasia, a type of pre-cancer. However, contrary to previous concerns, their risk is not affected if they use hormonal contraceptives, or by their history of pregnancy and childbearing, researchers have found.

Previous studies have suggested an increased risk of CIN with long-term oral contraceptive use and having more than one child, the investigators explain in the International Journal of Cancer, but such studies did not account for the possible confounding effect of cancer-related HPV infection.

Dr. Philip E. Castle from National Cancer Institute, Bethesda, Maryland and colleagues investigated the development of CIN in young women who tested positive for these types of HPV and had minimally abnormal Pap smears.

Among these women, the likelihood of finding CIN was no higher for current or former oral contraceptive users than for those who had never used the Pill, the team reports.

There was a marginal association with CIN and the current use of injectable or former Norplant use.

The number of pregnancies and children a woman had were not associated with being infected with the cancer-related strains of HPV, or with CIN in those who did have these infections, the researchers note.

Merry Christmas

Merry Christmas and Happy Holidays to all!

Cervical Cancer and the Kindness of Strangers

As you might recall, the clinical trial results for the human papillomavirus (HPV) vaccine have been most promising. Both Merck's Gardasil quadrivalent (16, 18, 6 and 11) HPV vaccine, as well as GlaxoSmithKline's Cervarix bivalent (16 and 18) vaccine have shown excellent promise.

Unfortunately, it appears effectiveness in preventing cancer is not enough. Not if you have the misfortune of being a female patient (emphasis mine):

Despite the obvious benefits, the vaccines may not be an easy sell: There are social and moral hurdles to overcome. "The biggest problem for companies will be convincing society of the need to vaccinate young girls against what is essentially a sexually transmitted disease," says Dr. Anne Szarewski, a clinical consultant at Cancer Research UK, which is conducting phase iii trials of Cervarix at Margaret Pyke Centre in London. Women worldwide had better hope Merck and GSK succeed.

So, all women can do is cross their fingers and hope that pharmaceutical companies [and/or politicians] have enough of a financial interest, or are benevolent enough to have their best interest at heart. Brilliant! Because, when it comes to making medical decisions, there's nothing like depending on the kindness of strangers. When did it become the accepted norm that female patients should be at the mercy of strangers in matters of health?

The South Dakota Task Force to Study Abortions Report

I started reading the report issued by the South Dakota Task Force to Study Abortions (via feministing). Unfortunately, I am unable to characterize for you what I've read so far; words fail me. So I will let one of the task force members do it for me:

Sen. Stan Adelstein, R-Rapid City, said he was upset that the report is filled with dishonest statements and is biased toward one religion....

"The report is theologically based, has patent untruths and misrepresentations, and no reasonable attention was paid to any amendments," the senator said.

Because the report is 72 pages long, and almost every paragraph contains something that needs to be corrected, debunked, and/or commented on, I plan to discuss the report in installments. Here's the first one.

First, a bit of background. At the beginning of this year, the SD legislature passed a bill (HB 1233) which created the South Dakota Task Force to Study Abortions. Its main duty was to study and, most importantly, to evaluate medical evidence, report its findings, and make recommendations as to the need for any additional legislation governing medical procedures [because we can never have enough of these laws and regulations]:

Section 3. The task force shall study the practice of abortion since its legalization, the body of knowledge concerning the development and behavior of the unborn child which has developed because of technological advances and medical experience since the legalization of abortion, the societal, economic, and ethical impact and effects of legalized abortion, the degree to which decisions to undergo abortions are voluntary and informed, the effect and health risks that undergoing abortions has on the women, including the effects on the women's physical and mental health, including the delayed onset of cancer, and her subsequent life and socioeconomic experiences, the nature of the relationship between a pregnant woman and her unborn child, whether abortion is a workable method for the pregnant woman to waive her rights to a relationship with the child, whether the unborn child is capable of experiencing physical pain, whether the need exists for additional protections of the rights of pregnant women contemplating abortion, and whether there is any interest of the state or the mother or the child which would justify changing the laws relative to abortion. The task force shall prepare a report detailing its findings, which shall include any proposals for additional legislation as it may deem advisable, and submit the report to the Governor and Legislature no later than December 1, 2005.

Earlier this month the task force issued its findings. According to press reports:

After a contentious final meeting, a state task force has recommended that the Legislature take further steps to restrict abortions in South Dakota.

The majority of the task force supported a report that says the 1973 U.S. Supreme Court ruling that legalized abortion was flawed because scientific and other advances have since demonstrated that life begins at conception.

The 72-page draft report calls for a ban on abortion by overturning the Roe v. Wade ruling that legalized the practice. In the meantime, it recommends that South Dakota should put further restrictions on abortion, such as requiring that women get additional information and counseling before having abortions.

Second, let's see what the task force chair and vice chair have to say about the report.

The assessment of Dr. Marty Allison, the self-identified "pro-life" task force chairwoman:

"It got to the point at the end that part of the task force members, as well as the vast majority of our public audience, left the meeting because it just got so ridiculous. It was an embarrassing end, to tell you the truth. I was disappointed in the process," Allison said.

More from Dr. Allison:

"The final report was authored by a few people on the task force, and it is less than completely objective and factual. It is biased and opinionated," said Dr. Marty Allison of Pierre.

Allison said she agrees with the report's call for a ban on abortion, with further restrictions on abortion in South Dakota until a ban can be accomplished. But the report does not reflect all the information that the task force gathered from experts and the public on both sides of the issue, and it does not deal with preventing unintended pregnancies and other important issues, she said.

"Even though I'm pro-life and it's a pro-life report, I couldn't support the entire document because of those reasons," Allison told The Associated Press.

"The process through which we came to the final report, through our meetings we had, I was disappointed with that. It's not reflective of all the information we spent so much time gathering," the physician said.

...

"The mentality of the task force was really an us-against-them mentality -- pro-life, pro-choice," Allison said.

Allison said she believes the task force should have approved a proposal requiring the report to include only rigorous scientific research that is accepted by the American Medical Association, the American Psychiatric Association, the American College of Gynecology and other professional organizations.

Next, we have this evaluation from the task force vice chair:

[S]everal task force members, including those who support abortion rights, walked out of a meeting Friday before the final vote. They said the majority, who oppose abortion, rejected proposals that would have helped reduce the number of abortions by reducing the number of unintended pregnancies in South Dakota.

...

Dr. Maria Bell of Sioux Falls, vice chair of the task force, was one of the members to walk out of the meeting. She said the process was one-sided and the majority's recommendations were not supported by information collected by the panel in the past few months.

Finally, let's take a look at the members of the task force. They are:

1. Dr. Marty Allison, Chair [voted against the report's recommendations]

2. Dr. Maria Bell, Vice Chair [walked out* before the final vote]

3. Senator Stanford Adelstein (R-Rapid City) [walked out before the final vote]

4. Senator Julie Bartling (D-Burke)

5. Mr. Travis Benson, J.D., Catholic Diocese of Sioux Falls

6. Mr. David Day, J.D., University of South Dakota law professor

7. Senator Jay Duenwald (R-Hoven), an officer in both the state and National Right To Life organizations

8. Senator Brock Greenfield (R-Clark)

9. Ms. Linda Holcomb MSW, Rapid City therapist, divorce professional

10. Representative Roger Hunt (R-Brandon)

11. Representative Elizabeth Kraus (R-Rapid City)

12. Ms. Kate Looby, Planned Parenthood of Minnesota/South Dakota Director

13. Representative Kathy Miles (D-Sioux Falls)

14. Senator Theresa Two Bulls (D-Pine Ridge)

15. Dr. John Stransky

16. Dr. Allen Unruh

17. Dr. David Wachs

[*Please note that I couldn't find a complete list of members who walked out, so it's possible there were more.]

So out of 17 members, only 4 are medical doctors, and one is a chiropractor. Moreover, of the 4 physicians, only one is an Ob/Gyn [you know, the specialty whose members are trained and experienced in routinely performing abortions]:

- Dr. Marty L. Allison, Pediatrician

- Dr. Maria Bell, gynecologic Oncologist (cancer specialist)

- Dr. John Stransky, Family Practitioner

- Dr. Allen Unruh, Chiropractor

Of note:

Dr. Unruh and his wife, Leslee, are the founders of the Alpha Center - a crisis pregnancy center in Sioux Falls - serving over 5000 clients per year.

[We'll come back to this, as this conflict of interest becomes significant when we look at the report's recommendations.]

One more thing about Dr. Unruh. From the Thomas More Law Center, a not-for-profit public interest law firm dedicated to the defense and promotion of the religious freedom of Christians, time-honored family values, and the sanctity of human life, whose purpose is to be the sword and shield for people of faith:

Leslee Unruh, a member of Right to Life for 25 years, and Director of the South Dakota Alpha Health Center, an abortion counseling service, whose husband helped start local Right to Life chapters throughout the state...

- Dr. David Wachs, Family Practitioner and 20-year member of an organization (the Aberdeen Area Right to Life) whose basic stated goal is to stop abortion.

Why are Dr. Unruh's and Dr. Wachs' anti-abortion advocacy, biases, and organizational affiliations significant (as well as those of Senator Jay Duenwald, for that matter)?

After all holding a particular set of personal or religious beliefs, whatever those might be, does not disqualify someone from serving on a scientifically-oriented task force. No, but being a closed-minded dogmatic does. If you are either unwilling, or unable to recognize, acknowledge and deal with reality, you have no place on a task force charged with evaluating medical matters. But I digress. Let's limit ourselves to the task force's words and actions for the answer to our question.

The members of the task force judge the credibility of witnesses, and the quality of their research based on the witnesses' admitted biases and the organizational goals of [their] employer. Advocating for reproductive choice and belonging to an activist organization that opposes all abortion regulation are the basis for judging a witness' opinions suspect and his research not credible.

From page 51 of the report (emphasis mine):

Dr. Stanley Henshaw also provided testimony on the physical and mental health effects of abortion. He is an advocate for reproductive choice and his employer is an activist organization that opposes all abortion regulations. He has been Deputy Director of Research for the Alan Guttmacher Institute, a Planned Parenthood special affiliate which is partially funded by Planned Parenthood Federation of America. The Task Force finds his opinions suspect and his research not credible due to his admitted biases and the organizational goals of his employer.

Again, according to the task force, the criteria used to judge credibility and competence are admitted biases and organizational affiliations. Not relevant education or profession. Not scientific fact. Not study methodology, or any of the other scientifically rigorous, established, and accepted criteria.

So what's the problem with [at a minimum] Drs. Unruh and Wachs, and Senator Jay Duenwald? According to the task force's own criteria, since they are advocates for lack of reproductive choice and members of activist organizations that support regulating abortion out of existence, with the admitted bias of stopping abortion, they are neither credible, nor competent. As such, they have no place on a task force to study abortions.

That's it for today. As soon as my neurons recover from the shock of reading through the report, I'll have more. But before I go, allow me to give you my general impression on what is currently going on in South Dakota: rampant malicious scoundrels are in charge.

Grand Rounds

This week's Grand Rounds are up.

Drug Policy, Bendectin, and Frivolous Litigation

I was reading this article on the FDA's increasing sensitivity to safety concerns (via Instapundit) and I couldn't help myself. My version of the article's conclusion:

If America's [reproductive-age] population is to get the new [or any] drugs it needs, policy makers must make decisions based on data, and resist speculation and public pronouncements by special interests.

Of course, my position is that policy makers shouldn't make any drug-related decisions, period, but it's good to see wide support for science-based policy, and noninterference in medical matters by special interest groups. Oh, wait, my mistake! This only applies when it comes to America's aging population [and a few select other populations, *cough* males *cough*].

One thing of note from the article is the mention of Bendectin. Although the drug was long off the market when I started out, I must say, every single time I heard an attending who'd used Bendectin talk about it, it was in glowing terms. No wonder, considering what happened after its withdrawal:

The most widely prescribed drug for nausea and vomiting of pregnancy (NVP), Bendectin, was voluntarily withdrawn from the US market in 1982, after numerous, unsuccessful lawsuits alleged it had caused birth defects.

After its withdrawal, hospitalization rates for NVP doubled while solid evidence of Bendectin'’s safety continued to accumulate.

Here's more on the Bendectin story, and the treatment of NVP, in general.

And since we're on the subject of NVP, I cannot emphasis this strongly enough: nausea and vomiting are NOT an inevitable part of the pregnancy experience. Please don't feel like you have to suffer in silence. Untreated, this condition gets worst before it ever gets better. And for some it can get quite bad, indeed. Hospitalization and parenteral nutrition while pregnant are truly miserable experiences. Please talk to your physician and ask for treatment!

Last, but not least, no mention of Bendectin would be complete without a lawyerly perspective.

Lybrel (Anya)

Good news about Lybrel, Wyeth's new continuous, low-dose (20 mcg ethinyl estradiol/90 mcg levonorgestrel) birth control pill. Lybrel, designed to be taken daily with no hormone-free intervals, showed complete ovulation suppression in a small study, and significant control of premenstrual symptoms in a larger, but not placebo controlled, study:

One study, involving 37 women aged 18-35 years, showed complete inhibition of ovulation in all women while on the oral formulation.

"We showed that none of the subjects developed follicles equal to or greater than 10 mm during treatment,"; said investigator Susan A. Ballagh, M.D., of the Contraceptive Research and Development program, Arlington, Va., of the Eastern Virginia Medical School, Norfolk.

Participants followed the continuous oral contraception (COC) regimen for 84 days, using three pill-pack segments.

After discontinuation of contraception, the time to return to normal ovulation--defined as serum progesterone levels greater than 5 ng/mL--was a mean of 20 days. A total of 95% of subjects ovulated within 25 days after discontinuation.

...

The second study found that the same COC regimen significantly alleviated premenstrual symptoms.

A total of 278 women with a history of cycle-related symptoms or dysmenorrhea were monitored during three cycles of the COC regimen, with no pill-free interval. The subjects maintained a daily diary, rating mood, behavior, pain, and physical symptoms using the Penn Daily Symptom Rating scale. Two-thirds of the women improved their scores by 50% in the first 28-day cycle (one pill pack). In addition, work productivity improved.

"What impressed me the most was the very immediate response of the first cycle and the strong response at end point," said lead investigator Ellen Freeman, Ph.D., of the University of Pennsylvania in Philadelphia. "Almost all the response occurred right away. That's fast. Secondly, I was surprised that all four of the symptom subscales seemed to respond similarly."

More from Wyeth here.

ETA: It appears the brand name in Canada and the EU will be Anya.

Plan B Lawsuit

Wisconsin Attorney General Peg Lautenschlager plans to sue the FDA for delaying approval of OTC sales of Plan B. According to Gov. Jim Doyle, who authorized the lawsuit:

The "FDA's postponements in making a decision is the result of politics, not science, and negatively impacts the health of women,"...

Commenting on Doyle's decision, Kelda Helen Roys, executive director of NARAL Pro-Choice Wisconsin, had this to say:

"His authorization recognizes that women's health should be more important than the political gamesmanship of conservative ideologues,"...

Granted, the AG's stated motivation for the lawsuit is the extra cost the state could incur as a result of the approval delay. But looking at the big picture, one thing is clear: if the problem with the FDA's decision is that politics, as opposed to science, played the deciding role, using lawsuits to rectify the problem is not the way to go. Lawsuits are not part of the scientific method [yet! We can only hope for the day when politicians, lawyers, and assorted religious fundamentalists prevail, and we're finally able to practice medicine devoid of science.].

In my opinion this is like treating the symptoms without addressing the cause. A court of law (or, for that matter, the political arena) is not the appropriate venue to decide whether Plan B should, or shouldn't be available OTC. Alternatively, if you really must go the lawsuit way, I say do it the right way. Start making Plan B available OTC immediately, in defiance of the FDA's political ruling, and force the politicians who object to make a [scientifically sound] case against it.


(via NARAL)

Grand Rounds

One of our favorite bloggers is hosting this week's Grand Rounds.