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Uterine Fibroid Embolization
Endometrial Ablation
Female Reconstructive Surgery
Clinical Trials/Research

Clinical Trials/Research

"If we knew what it was we were doing, it would not be called research, would it?"

Albert Einstein

On June 3, 2004, the Food and Drug Administration coordinated a meeting of the Obstetrics and Gynecology Devices Panel of the Medical Devices Advisory Committee to review the InSightec ExAblate 2000. This medical device is currently under clinical investigation for its safety and efficacy in the treatment of uterine fibroids.

After spending a considerable amount of time reviewing darn near every single piece of literature on the technology of focused ultrasound -- including clinical investigation materials for prostate cancer, breast cancer, liver cancer, and brain tumors -- and then reviewing the data presented thus far on this technology for uterine fibroids, I honestly cannot see how the FDA Panel would even consider recommending the approval of this device for treatment of uterine fibroids at this time with a limited amount of abysmal data.

But, sadly, it did.

The panel voted 8 to 5 for approval. Women dropped out of this study in the DROVES -- with a total of 61.5% of the 109 women enrolled with an "Intent to Treat" as subsequently being listed as a "loss to follow-up" by 12 months or as failures who went on to some other treatment. To put this into perspective, the FDA has indicated a 15% loss to follow-up rate as the maximum amount acceptable in other clinical trials. For reasons unbeknownst to me, this panel completely ignored the high number of women dropping out of this study. What in heaven's sake happened here?

Some news agencies have reported the following:

"According to clinical trial results presented by both InSightec and the FDA during the panel meeting, patient symptoms improved by about 71% over a six-month period. This surpassed the main goal of the trial, which was 50% success rate at six months."

Um, this statistical information is taken so blatantly out of context with the data presented as to actually be deliberately misleading. While it's not showing up in any of the press releases from Insightec, it is being spouted by their clinical investigators to the media and showing up in news stories anyway. (SIDENOTE: This may be a naive/ignorant question, but aren't clinical investigators hired/paid by a company accountable for their potentially misleading statements made to the press which could possibly be published in a manner which might influence the stock of a company? Or, do we simply write it off as poor journalism and trust that those quoted did, in fact, communicate the fuller picture to the media???)

You see, this 71% improvement rate is calculated on only those patients still "evaluable" in the study at the end of 6 and 12 months. It was not based on the collected data of all 109 patients enrolled with an "Intent To Treat."

Fact: This study consisted of 109 patients identified as being enrolled with "Intent To Treat". However, there were only 91 women left in the study at the 6 month mark (3 withdrew, 11 considered "non-evaluable", and 4 treatment FAILURES). By the 12 month mark, only 42 women were left in the study. These 42 women were then considered the "Evaluable" group. Out of the "Evaluable" group, there was indeed improvements in their symptom severity scores.

Fact: This study included women enrolled from 7 different clinical sites. This begs the question of how consistency in application was truly applied. Especially in relationship to the devices and software used at each site AND the differences in gyn/radiology clinical settings and care.

Number of Patients (Total 109)
24 (22%)
Sheba (Israel)
20 (18%)
St. Mary's (England)
19 (17%)
Johns Hopkins
16 (15%)
12 (11%)
Charite' (England)
9 (8%)
Hadassah (Israel)
9 (8%)

FACT: According to the FDA presentation on the Insightec data, 65 patients in this study FAILED TO MEET THE DEFINITION OF SUCCESS AT 12 MONTHS!

For those of you interested in this nonsurgical treatment for symptomatic fibroids, the following documents and websites may be of interest:

InSightec ExAblate® 2000 (P040003)

FDA Agenda
FDA Roster of Panel Member Attendees
FDA Discussion Questions

My written statement submitted to the FDA in response to the data presented/FDA Discussion Questions

In the end, we are all responsible for our choices -- and, I can only say that right now I'm very, very glad this treatment option was not in clinical trials during the time period when I was so desperately in need of relief from fibroids. I would have jumped at the chance of signing up for this. And, I probably would have been one of those who were counted as a 'loss to follow-up' in the data, too. Why? Because focused ultrasound might have killed one fibroid and left the other three to take off and blossom and then I'd be back where I started again with nowhere to go.

You see, even with the approval of this device, the use of MRI makes it too expensive for any insurance company to allow a patient to be treated over, and over, and over again with it. And, once this device is approved for the treatment of cancerous tumors (in the future), a fibroid patient will be so low on the totem pole of treatment priority as to be buried 6 feet under. (That is to say, it will be in such high demand for more critical masses that it will be a "dead on arrival" treatment for women with uterine fibroids!)

So, why was this device tentatively approved on such limited data and evidence of safety and efficacy to the patients? A very good question, indeed. Wish I had the answer. I don't. However, I do have a few thoughts about what MAY have contributed.

In the end, my thoughts on the FDA review/approval process currently in place are NOT kind. In fact, they're pretty damn ugly. Yet, this is the agency that oversees our health and safety in the medical community. Oy. I guess, well, it's better than nothing...

As for focused ultrasound...I am -- believe it or not -- a strong supporter of this technology. Particularly for brain tumors. Which, afterall, was what the original scientific, medical, conceptual plan was all about. Eliminating the horrific surgical burden that patients with brain tumors currently face. My sister has had two brain tumors removed in her lifetime and both surgeries were horrific and the time period spent on recovery a nightmare. Yes, I am incredibly excited about the prospects of this technology for the zapping of brain tumors in a nonsurgical manner.

As for fibroids? Well, I stand by my written statement to the FDA. Without question.

Now, if you've read this far but still haven't clicked on any of the links above or read my written statement to the FDA, then I think it is critical for you to also read the following excerpt. Afterall, the clinical investigators have NOT made it a practice to share this information with the media and the media certainly has made no attempts whatsoever to figure this out on their own and ensure that potential patients are aware of these details.

Exclusionary Considerations (items that would make you a bad candidate for this procedure)

Patient exclusionary criteria appears to be absent from public review but is absolutely essential to the very offering of HIFUS to women with fibroids. The following items should be seriously reviewed and considered in pursuing the treatment of focused ultrasound:

In addition, the following exclusionary items related to ultrasound, contrast, and MRI should also be reviewed:

Site Name/Author
What You'll Find
National Institute of Environmental Health Sciences (NIEHS) & National Center for Research on Minority Health and Health Disparities (NCRMHD) Fibroid Growth Study. The Fibroid Growth Study (FGS) is designed to investigate why some fibroids grow to become health problems while others do not. Enrolling patients through University of North Carolina hospitals.
Agency for Healthcare Research and Quality (AHRQ) Evidence Report/Technology Assessment: Number 34: Management of Uterine Fibroids. This link is for the summary report but the full 200+ page report is also available as a zipped file from the AHRQ. A MUST read for all who are interested in reviewing the research (or, lack thereof) on uterine fibroids to date.
National Institute of Environmental Health Sciences
Dr. Barbara J. Davis
An Approach to Study Women's Health and the Environment. Background information on the NIEHS and Center for Research on Minority and Health and Health Disparities Fibroid Growth Study. Cardiovascular and Interventional Radiology Research and Education Foundation(CIRREF) UAE Fibroid Registry. Patient registry to evaluate the safety and efficacy of uterine artery embolization (UAE) for the treatment of uterine fibroids.
Population Council Clinical background info on mifepristone (RU-486).

Dr. Aaron Kromhout (Phoenix, AZ)

Research project examining the use of Lupron in combination with UAE. Center for Uterine Fibroids
Brigham and Women's Hospital
Dept. of Obstetrics, Gynecology and Pathology
Ongoing research studies on the causes of fibroid-related symptoms by investigating the hormonal, genetic, and molecular processes of fibroid growth and development. Also: the development and testing of innovative treatment options for uterine fibroids including growth factor-directed therapy and gene therapy. National Library of Medicine PubMed: NLM's search service to access the 9 million citations in MEDLINE and Pre-MEDLINE (with links to participating on-line journals), and other related databases.
Article reprint courtesy Brigham and Women's Hospital
Theories of Fibroids
CenterWatch: Clinical Trials Listing Service Identifies some clinical trials on Uterine Fibroids in U.S. by state.
Norris Medical Library
Online Reference Center
Quick links to the following:
- California Healthline
Daily electronic news briefing on California and national health policy and industry news from more than 300 news sources, including California and national newspapers, wire services, health care journals and trade publications.
- Doctor's Guide to Medical & Other News Browse news stories by the week, month, subject or keyword.
- Reuters Health
A browsable list of health news stories. Includes two databases: Professional Medical News and Health eLine.
- U.S. Medicine Information Central A source of U.S. Federal medical news
Gynecare, the women’s health division of ETHICON, INC. 4/16/99 New Clinical Trial Recruits Women Who Have Excessive Menstrual Bleeding : Patient enrollment is beginning for a clinical trial to evaluate a new surgical treatment for excessive menstrual bleeding, or menorrhagia. The new trial, called the CARMEN study, will seek to establish the safety and efficacy of a device that uses cryoablation to freeze and remove the endometrium, the lining of the uterus. ETHICON, INC. will enroll 260 women across 10 sites and randomize them to receive cryoablation or an alternative procedure that uses electrosurgical equipment to remove the uterine lining. Women participating in the trial must have excessive menstrual bleeding, be pre-menopausal, and have concluded childbearing. Women interested in participating in the study can call toll-free 1-800-572-5059. National Institute of Health
(Health Information page)
Access to consumer health publications, clinical trials, health hotlines, Grateful Med, and the NIH Information Index (a subject-word guide to diseases and conditions under investigation at NIH). Agency for Healthcare Research and Quality AHRQ, formerly entitled the Agency for Health Care Policy and Research (AHCPR), was established in December 1989 under Public Law 101-239 (Omnibus Budget Reconciliation Act of 1989). AHQR, a part of the U.S. Department of Health and Human Services, is the lead agency charged with supporting research designed to improve the quality of health care, reduce its cost, and broaden access to essential services. NIH Testimony; Hysterectomies
Department of Health and Human Services

5/5/93 Statement by Dr. Vivian W. Pinn
Director of the Office of Research on Women's Health
National Institute of Health
Health Subcommittee on Aging
U.S. Senate Committee on Labor and Human Resources

Presentation of statistics on hysterectomy in the U.S., current causes for and efficacy of hysterectomy, identification of ongoing research conducted by a variety of agencies.
The National Institutes of Health The National Heart, Lung, and Blood Institute WOMEN'S HEALTH INITIATIVE The WHI is one of the largest preventive studies of its kind in the United States focusing on the major causes of death, disability and frailty in postmenopausal women. The overall goal of WHI is to reduce coronary heart disease, breast and colorectal cancer, and osteoporotic-fractures among postmenopausal women via prevention/intervention strategies and risk factor identification. The WHI is a 15 year research program.
British Medical Journal
1995;311:593 (2 September)
One Hundred Years Ago On Over-Operating in Gynaecology (1895)

Some history to put gynecological medical research in perspective. The British Medical Journal Interesting site containing "original scientific studies, ... educational articles, and papers commenting on the clinical, scientific, social, political, and economic factors affecting health."

Female Reconstructive Surgery


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This page last updated Thursday, June 9, 2004