Jeffrey Shuren, M.D., J.D., the Director of the Center for Device and Radiological Health at the Food and Drug Administration, replied to an open letter from the Leiomyoma Morcellation Review Group. You can read the original open letter here, and view Dr. Shuren’s reply in the images below.
The Leiomyoma Morcellation Review Group sent the following letter to the FDA in response:
Dear Dr. Shuren,
Thank you for your response to our letter and for your invitation to continue the dialog regarding the FDA’s restriction on the use of the morcellator for the majority of women with uterine fibroids. We respect the FDA’s difficult position in this matter, especially considering the adverse publicity and pressure generated by Dr. Reed’s husband. As responsible physicians and women’s health-care advocates we think that women who need treatment for uterine fibroids, as with all patients, deserve to make treatment decisions based on the best information available. We know that this is also something that the FDA believes as well. We would like to make the following comments:
1) As we are sure you are aware, a recent publication from the Michigan Surgical Quality Collaboration showed that the rate of laparoscopic hysterectomies decreased and the rate of abdominal hysterectomies increased following the FDA’s restrictive policy on morcellation, and there was an associated concomitant increase in major surgical complications and 30-day readmissions to the hospital (Harris). This increase in morbidity was anticipated by the decision analysis published by Siedhoff and colleagues. Unintentionally, the FDA is compromising the health of some women. Our concerns regarding higher surgical morbidity associated with increased use of laparotomy for women needing surgical treatment for fibroids drove our decision to prepare our letter questioning the FDA’s guidance regarding morcellation. Unfortunately, our concerns are now validated by published data.
2) In our letter to the FDA and our commentary published in Obstetrics and Gynecology, we did “challenge” your methodology and calculation of the prevalence of leiomyosarcoma among women having surgery for presumed fibroids, as well as the impact of electro-mechanical morcellation on survival. We are very concerned that your researcher did not carefully consider all of the published data available at that time. We are also concerned that the FDA analysis was reported to be performed by a close friend of Dr. Noorchashm and that this conflict of interest was not disclosed during the hearing.
The Kaiser study that you cite is only one of many recent attempts to determine the prevalence of LMS among women having surgery for uterine fibroids. In a further analysis, we added the women from the Bojahr study cited by us and the Raines-Bennet study cited by you and re-calculated our meta-analysis. The rate of LMS then becomes 1:1924 or 0.052% and essentially no different from our original calculation.
3) In the Kaiser study you cite, our concern is that it appears that you incorrectly state that “the adjusted risk ratio for death at one year for power morcellated uteri was significantly greater compared to uteri that were not morcellated”. In fact, there was no difference in one year survival in these groups of women, as noted in the abstract and indicated in Figure 3. The only statistically significant finding in that analysis was the one-year comparison of women with any type of morcellation compared with no morcellation, suggesting that power morcellation is not the determining factor. The analysis also showed no increased mortality at 2 or 3 years, consistent with an aggressive disease that has early spread by the hematogenous route.
Additionally, the FDA did not carefully considered the published literature. Indeed, the data used to determine that laparoscopic power morcellation “significantly worsening the patient’s long-term survival” has been criticized by us and others for being of poor quality characterized by heterogeneous referral populations, small numbers and suboptimal quantitative analysis.
Furthermore, since the vast majority of cases analyzed in the literature were morcellation procedures performed using a scalpel via either the vaginal or mini-laparotomy routes, it would seem reasonable to restrict of vaginal and mini-lap morcellation in addition to electro-mechanical morcellation. Such a restriction would essentially limit surgical options for women with fibroids to total abdominal hysterectomy, a position that would be called into question by most women and their gynecologists.
We respect the concerns of the FDA staff. However, the FDA’s decision to place a boxed warning, albeit intended to protect women and to make them aware of risks, has in fact reduced treatment options for women, paradoxically increasing the risks associated with surgery for uterine fibroids. Although we are not questioning your intentions, your agency’s actions do not appear consistent with your mission to ensure the safety and health of all women.
4) While we agree that a registry might clarify the prevalence of LMS and the influence of morcellation on survival, the registry would need to be mandatory for all US women with uterine LMS. With such a rare condition, anything less would be subject to significant selection and reporting bias. We are aware that a registry of women with leiomyomas is currently being developed through funding from PCORI and that this will provide important prospective data. It will be essential to have appropriate funding for an LMS registry as well. We sincerely hope that the FDA is discussing this need with your sister federal agencies.
Women and their physicians look to the FDA for guidance on issues that impact public health and safety. We do not feel that women have been properly served by the FDA’s current morcellation advisory. We request that the FDA reconsider the currently available data and re-evaluate the restrictions on the use of the electro-mechanical morcellator for the majority of women with uterine fibroids. We welcome the opportunity to talk to you about these issues and would be willing to send a group to Washington for further discussion if you wish. We are confident that the FDA shares with our group a common concern for the health and safety of all women with leiomyomas. Our goal is to find a way forward that will provide an appropriate and reasonable approach to uterine leiomyoma treatment and medical care.
Thank you for your consideration,
William H. Parker, MD, Santa Monica-UCLA Medical Center
Andrew M. Kaunitz, MD , University of Florida College of Medicine–Jacksonville
Elizabeth Pritts, MD, Middleton, WI
David Olive, MD, Middleton, WI
Eva Chalas, MD, FACOG, FACS, Winthrop-University Hospital, Mineola, NY
Daniel L. Clarke-Pearson, MD, UNC-Chapel Hill
Jonathan S Berek, MD, MMS, Stanford University School of Medicine
Barbara Goff, MD, University of Washington, Seattle, WA
Robert Bristow, MD, UC Irvine School of Medicine
Robin Farias-Eisner, MD, David Geffen School of Medicine at UCLA
Amanda Nickles Fader, MD, Johns Hopkins Medicine
G Larry Maxwell, MD, FACOG, COL(ret) U.S. Army, Inova Fairfax Hospital
Scott C Goodwin, MD, University of California, Irvine
Susan Love, MD, Dr. Susan Love Research Foundation, Los Angeles, California
William E Gibbons, MD, Baylor College of Medicine
Leland J. Foshag, M.D., FACS, John Wayne Cancer Institute, Santa Monica, California
Phyllis C. Leppert, MD, PhD, Duke University School of Medicine
Charles W. Nager, MD, UC San Diego Health System
Judy Norsigian, Our Bodies, Ourselves, Boston, Mass
Timothy Johnson, MD, University of Michigan
David S. Guzick, MD, PhD, University of Florida
Anton J. Bilchik, MD, PhD, FACS, John Wayne Cancer Institute, Santa Monica, California
Hugh Taylor, MD, Yale School of Medicine
Richard J. Paulson, MD, Keck School of Medicine, University of Southern California
Professor Cindy Farquhar, University of Auckland, NZ
Sawsan As-Sanie, MD MPH, University of Michigan
Linda D. Bradley, MD, Cleveland Clinic
Stacey A. Scheib, MD, Johns Hopkins Hospital
Carla Dionne, MPH, MBA, National Uterine Fibroid Foundation
Laurel W. Rice, MD , University of Wisconsin-Madison School of Medicine and Public Health
Alison Jacoby, MD, University of California, San Francisco
Charles Ascher-Walsh, MD, Mt. Sinai School of Medicine
G. David Adamson, MD, Stanford University School of Medicine
Matthew Siedhoff, MD MSCR, University of North Carolina at Chapel Hill
Robert Israel, M.D, Keck School of Medicine, University of Southern California
Marie Fidela Paraiso, MD, Cleveland Clinic
Michael M. Frumovitz, M. D., M.P.H., FACOG, FACS, The University of Texas MD Anderson Cancer Center
Guy I. Benrubi, M.D., University of Florida College of Medicine – Jacksonville
Steven S. Raman, MD, David Geffen School of Medicine at UCLA
Rosanne M Kho MD, Columbia University Medical Center
John R Lurain, MD, Northwestern University Feinberg School of Medicine
Ayman Al-Hendy MD PhD FRCSC FACOG CCRP, Medical College of Georgia
Ted L. Anderson, M.D., Ph.D., Vanderbilt University School of Medicine
R. Kevin Reynolds, MD, FACS, FACOG, University of Michigan
John DeLancey, MD, University of Michigan Health System