OWH-Funded Research: Medical Device Safety
The FDA Office of Women’s Health (OWH) awards research grants for 1-2 year studies to support FDA regulatory decision-making and advance the science of women’s health. OWH has funded research projects that address health issues affecting women across their lifespan. This page highlights OWH-funded research related to device safety.
Computational models to evaluate the safety and effectiveness of vaginal heat therapy devices - David Birsen/CDRH (19)
Vaginal heating devices are energy-based devices consisting of laser, radiofrequency (RF), and ultrasound technologies that apply heat to the vagina. Vaginal heating devices have become increasingly popular in recent years for use as a non-hormonal treatment for symptoms of menopause, as well as for women seeking aesthetic vaginal rejuvenation procedures. The aim of these devices is to heat the vaginal tissue within a therapeutic range to stimulate a wound healing response, but below the thermal dose at which permanent tissue damage occurs. However, the heating effects of laser, ultrasound, and RF devices on vaginal tissue have not been robustly studied or characterized. Device manufacturers evaluate vaginal tissue heating using computer simulations and/or bench testing, but these test methods have not been validated and their clinical utility is not established. This raises safety concerns regarding unintended thermal injury when these devices are used in humans, as well as significant regulatory obstacles when evaluating these devices for marketing submissions. The goal of this project is to develop and validate test methods that can be used to reliably assess the safety and performance of vaginal heating devices. Specifically, this project will develop computational models to simulate vaginal heating in the human anatomy due to the heat produced from laser, RF, and ultrasound devices. This study will provide tools to aid FDA reviewers in assessing the safety of vaginal heating devices prior to use in humans, as well as provide device manufacturers with validated methods to conduct non-clinical testing.
Development of a Standardized Protocol for Screening and Detection of ALCL and implant Rupture through High Resolution 3D MRI Imaging of Silicone breast Implants - Sunder Rajan, PhD/CDRH (18)
The advent of newer silicone gel breast implants has led to longer life, due to better shell design. Despite the improvement in design, Post-market clinical studies have demonstrated a significant prevalence of silicone breast implant (SBI) ruptures. Ironically, the longer life of the implants has also contributed to an increase in the incidence of Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). BIA-ALCL is suspected of being caused by the texture design of the newer implant shells and there is a significant concern that the incidence will continue to increase. It is believed that public awareness of BIA-ALCL will also lead to an increased need to imaging based diagnostic screening.
FDA recommends that women with SBI, be screened regularly for implant failure. Magnetic resonance imaging (MRI) is the preferred diagnostic technique for the evaluation of implant rupture. Currently, the MRI clinical scan protocols involve several complex individual scans that provide two-dimensional images in different orientations which are also difficult to interpret because of the complex folds and structure around a breast implant. We hypothesize that a simple volume scan which allows for high definition image slices in any desired orientation, will allow for better and easier diagnosis. It will also allow for better visualization of the wall of the implant and any surrounding liquid (seroma). We recently conducted a pilot study using such a 3D protocol, which provided additional diagnostic information and confidence. However, for robust clinical translation this method needs to be implemented and standardized by the MRI instrument vendors. Standardization of the 3D method will allow for reproducible MRI image quality from site to site. We propose to use a custom test object which contains components to mimic a human breast with implants. The phantom will be utilized to implement the 3D protocol with the collaboration of MRI vendor scientists to generate comparable signal behavior. This quality controlled protocol will be implemented in approximately 10 MRI facilities in preparation for a multicenter clinical trial.
Identifying the Impact of Surface-Texturing on the Pathogenesis of Breast Implant Associated- Anaplastic Large Cell Lymphoma - Hainsworth Shin, PhD/CDRH (18)
This proposal explores a possible explanation for incidence of breast implant associated-large cell lymphoma (BIA-ALCL). BIA-ALCL is a rare lymphoma that afflicts women with breast implants (BIs). FDA recently released safety communications linking BIs with BIA-ALCL. While the risk for BI recipients to contract BIA-ALCL is estimated to be low at 0.1-0.3 per 100,000 women per year, this estimate represents a troubling trend especially since it may be based on incomplete data. At minimum, FDA must respond to this risk estimate to protect women from this disease. Very little is known about how BIs cause BIA-ALCL. Recently, FDA with the American Society of Plastic and Reconstructive Surgery (ASPRS) reported a significant correlation between BIA-ALCL and BI surface texturing. Most, if not all, cases of BIA-ALCL were for women with textured BIs. Surface texturing increases the BI surface area and introduces pockets that encourage tissue ingrowth. This can have two effects. First, it anchors BIs in host tissues differently than smooth implants, which causes them to a move differently due to bodily activity (e.g., walking, breathing). These different movement patterns create a unique mechanical force environment for the cells in the implant site, which may enhance the body’s inflammatory response. Second, texturing increases the contact area and numbers of protective pockets for bacteria to grow. Bacterial biofilms also enhance inflammation. This research tests the possibility that chronically high levels of inflammation resulting from either of these two effects or both results in BIA-ALCL. We expect to learn key information about the origins of BIA-ALCL, which can be shared with the public, including the device industry and medical communities. This information will also help FDA develop new assessment approaches to help with the regulatory review of BIs, as well as other implants that incorporate surface texturing.
Virtual model of a female human subject with large body habitus for use in MR Radiofrequency safety assessments - Angelone Leonardo, PhD/CDRH (17)
The goal of this project is to generate a computational anatomical model of a human female adult subject of large body habitus. The model, proposed initially for analysis of radiofrequency induced heating during MRI, will be freely available to stakeholders in the scientific and industry. More than 35 million Magnetic Resonance Imaging (MRI) scans are performed in the US each year, making MRI an important diagnostic tool. MRI’s energy is tightly controlled by international regulatory standards, and well-established guidelines bolster patient safety. In addition, unlike computer tomography scanning (CT scanning), MRI does not use ionizing radiation, but rather makes images of the internal structures of the body by using specialized coils to send and receive RF energy. All medical devices carry some risk—for MRI, one possible risk is excessive RF-induced heating of tissue with possible thermal damage. RF-induced heating depends on several variables, including geometry of the coil, the patient’s position (imaging landmark or body posture), and the patient’s anatomy. Computational modeling has been largely used over the past decade to investigate RF-induced heating of patient tissue undergoing. Several human body models, such as the Virtual Family (Christ et al. 2008), the Visible Human Male and Visible Human Female (Visible Human Project) are currently available to the scientific community for analysis of RF-induced heating. However, there are no models validated against direct experimental data that represent the anatomy of a female subject of large body habitus. Because RF heating depends on the patient dimensions and body posture, the project aims to fill such gap and generate a computational model of a human female subject of large body habitus for RF-induced heating analysis. The model will also be validated experimentally with measurements in MRI, ultimately allowing for the assessment of the potential risk of injury over a broader sample of patient population.
Development of test methods to evaluate the risk of cancer-cell permeation through tissue containment bags during laparoscopic power morcellation of uterine fibroids - Matthew Myers, PhD/CDRH (16)
Laproscopic power morcellators are medical devices used to excise uterine fibroids in to small fragments which could then be removed from the abdomen through small incisions as a minimally invasive procedure. However, in recently published safety communications, FDA has pointed out that power morcellators carry the risk of spreading cancer cells within the abdomen and pelvic regions while fragmenting the fibroid tissue. To minimize the risk of spreading the cancerous tissue, some studies have recommended the use of a tissue containment bag, which surrounds the power morcellator and forms a barrier between the tissue and the abdomen. The tissue-containment bags are made out of polymers which are supposedly packed tight to prevent any penetration of the cancer cell through the pores present in the membrane. The device manufacturers evaluate the performance of these devices by testing them in a static environment which does not mimic the forces experienced by the tissue bags during power morcellation. The goal of is study is to develop new test methods that could test the integrity of the tissue containment bag in the presence of forces imparted by the power morcellator. This study will also develop computational models to assess whether cancer cells can permeate tissue containment bags during the surgical procedure. The results published by this study will aid FDA reviewers in the development of a new guidance document for testing the safety and performance of tissue-containment bags.
Improving assessment of spinal device subsidence by incorporating female anatomy and density - Srinidhi Nagaraja, PhD/CDRH (16)
Patients with severe neck or low back pain are often treated with spinal medical implants such as interbody cages or total disc replacement devices. Although these are relatively successful procedures, it is possible for the device to push into the top or bottom of the vertebra. This is referred to as device subsidence. If severe, the patient may experience more pain or loss of back flexibility. This is an important issue for women’s health as many older women have neck and low back pain that may require implantation of spinal devices. It is unknown, however, if implant subsidence occurs more frequently in women because of osteoporotic changes leading to lower bone density and poorer bone quality than men. Therefore, the goal of this study is to better understand factors that put a patient at risk for implant subsidence. By using experiments and computer simulations, our goal is to develop a method that can better predict if this adverse event may occur when a spinal device is used to treat these patients.
Development of the US Women's Health Coordinated Registries Network- Nilsa Loyo-Berrios, PhD, Special Funding/CDRH (16)
Background: Historically, scientific questions that uniquely affect women (e.g. pelvic floor disorders, uterine fibroids, female sterilization) have been evaluated in stand‐alone studies. When targeted registries were created, linkage to other data sources was not possible, missing the opportunity to create infrastructure to advance women’s health in the continuum of routine clinical practice. Therefore, we propose to create a “Coordinated Registries Network” (CRN), which will serve as the national infrastructure for the evaluation of medical devices in clinical areas unique to women. Specific objectives: to, (1) establish a Public‐Private‐Partnership (PPP) with stakeholders; (2) identify/prioritize clinical conditions and devices unique to women; (3) convene an “Expert Core Working Group”; (4) establish convener group within MDEPINet; (5) hold stakeholders workshops at FDA Campus; (6) create a robust consortium of registries that can incorporate IDE and postmarket mandated studies into their infrastructure. Methods: Key stakeholders will be identified and invited to join the Expert Core Working Group, which will be charged with: (1) identification of clinical conditions and device areas to prioritize, (2) evaluation of existing efforts and models that can be applied in the realm of women specific devices/health issues, and (3) selection of the convener group within MDEpiNet. The convener group will coordinate CRNs work per identified priority areas, and will develop the business and sustainability model. CRNs will allow for data involving diagnostic and treatment modalities to be captured in a “Suite” of registries. The individual registries would operate under the auspices of health care professional societies (e.g. ACOG, AUGS, ASPS, etc.), ideally sharing a common platform, analytical and support infrastructure, while maintaining the flexibility necessary to address specific questions unique to the clinical conditions covered by the respective registries. The infrastructure will also incorporate premarket (IDE) and postmarket mandated studies, which will limit startup costs and implementation time of clinical trials as well as review time for FDA to evaluate premarket applications or postmarket submissions. FDA has preliminarily identified the following areas of concern: uterine fibroids, abnormal uterine bleeding (non‐fibroid related), contraception methods, stress and urge urinary incontinence, fecal incontinence, pelvic organ prolapse, urinary retention, outcomes for breast implants, cosmetic surgery, obesity, infertility, reproductive cancer detection and treatment, labor and delivery, pregnancy and postpartum, menstruation, sexual function, and TMJ disorders. Collaboration has already begun with the COMPARE‐UF Registry, and discussions have taken place to adapt the registry for collection of data on medical devices used during treatment of uterine fibroids.
Advancing Methods for Assessment and Prediction of Clinical Performance of High Intensity Therapeutic Ultrasound Systems- Keith Wear, PhD, Special Funding/CDRH (16)
High Intensity Therapeutic Ultrasound (HITU) is a new minimally-invasive alternative to surgery. HITU shows great promise for many women's health conditions including uterine fibroids, breast cancer, breast fibroadenoma, uterine adenomyosis, tubal pregnancy, fetal surgery and polycystic ovary syndrome. HITU can destroy diseased or unwanted tissue but can also destroy healthy tissue because of the difficulty of precise dosage and localization of HITU energy in the body. The proposed project aims to develop computational and experimental methodology to improve standardization and objective characterization of HITU systems. The project contains five parts: 1) development and validation of software (to be made publically available) for modeling HITU systems, 2) development and validation of radiation force balance methods for measuring HITU acoustic output power, 3) development and validation of methods for broadband characterization of tissue-mimicking materials used in HITU system characterization, 4) investigation into dependence of HITU output measurements on the type of hydrophone used, and 5) development and validation of a model for correcting needle and fiber optic hydrophones for low-frequency distortion.
Bacterial colonization and biofilm formation in dermal fillers implants: An in vivo model to confirm in vitro findings and pathogenesis leading to adverse events - Kenneth Phillips, PhD, CDRH (15)
The use of dermal fillers (DF) to address contour defects resulting from aging, disease, and trauma is increasing exponentially (over 1.7mil. in 2011, >91% in women). Infections are a concern for permanent DF and can lead to disfiguring necrosis/scarring or result in bacteremia. Removal of DF can damage tissue and long-term antibiotic therapy can lead to multi-drug resistant infections. Patients suffer social and psychological trauma. This work sought to understand how to make DF use safer by targeting two intervention areas: 1)Novel simulated skin and pigskin models were developed to study how to reduce contamination during injection; 2)A novel flow cell insert was developed to how study how chemical and mechanical properties of DF affected S. aureus adhesion and 24h biofilm formation. The results can be used to develop evidence-based regulatory and clinical recommendations, and show how infection rates might be lowered by developing improved DF.
The effects of gender differences in adverse events for integrated fixation spinal implants - Srinidhi Nagaraja, PhD/CDRH (15)
Integrated Fixation (IF) interbody spinal cages are medical devices used to treat patients with degenerative disc disease, radiculopathy, and/or myelopathy. As a new approach to spinal fusion, these devices have the potential to reduce complications and morbidity. However, the safety of these devices may be a concern where adverse events such as endplate subsidence (i.e. the device migrates into the vertebral body), device loosening, and bone fracture resulting in pain and revision surgery have been observed clinically. This is of particular importance in women as adverse events in females occur at a greater rate than in males (Lastfogel et al. 2010). This study has direct regulatory impact and relevance to women as it identifies how sex differences in bone quality and spinal flexibility affect the mechanical integrity of these devices after implantation. This coincides precisely with the Agency’s mission to provide safe and effective medical devices to all patients in the US, particularly for subgroups such as women who may have higher rate of adverse events due to these gender specific differences.
Sex-specific modeling and analysis of ACL injury susceptibility - James Coburn/CDRH (15)
More than 130,000 anterior cruciate ligament (ACL) repairs are performed each year. Athletes are the primary recipients, with female athletes 3-6 times more likely to suffer from ACL tears than males. Non-athletes may also require ACL repair due to an accident or a condition that increases their risks. Tests that screen for susceptibility to ACL injury are made for athletes and involve high impact activities. For those with compromised movement or other risk factors (e.g. elderly), they may not be an option. This research project has two aims. The first is to use existing and new data gathered from subjects performing specific activities to develop a low impact metrics to assess ACL injury susceptibility. The second is to develop a computational model of the knee ligaments to aid the regulatory review of medical devices to repair the ACL.
Identifying and characterizing key mechanical characteristics of surgical meshes used for pelvic organ prolapse repair and treatment of stress urinary incontinence in women (Supplementary Funds) - Terry Woods, PhD/CDRH (15)
Over 300,000 American women each year have surgery to treat conditions like leaking of urine that you cannot control and organs in the pelvis falling out of place. Many of these surgeries include mesh implants. Both conditions have considerable women’s health impact, including reduced sexual, urinary, and bowel movement function. There has been an increase in reported adverse events with numbers approaching 1000 per year. Mesh exposure through adjacent tissue is the most commonly reported mesh-specific problem. Researchers believe mesh stiffness influences exposure through tissue, thus, development of improved methods to evaluate stiffness is crucial. When sponsors of new surgical mesh applications submit stiffness information, the test methods used vary between devices, making comparison of devices difficult. There is also a general lack of understanding of the effects of stiffness and mesh properties on device function. This study will develop standardized test methods to describe mesh behavior. These methods will be included in revised guidance documents, leading to more consistent and timely reviews. This should reduce device development time for industry by better defining required preclinical testing. This will support the CDRH vision of providing safe, effective, and high-quality medical devices to the American public first in the world.
Inclusion of Minority Racial/Ethnic Subjects in OB-GYN Device Applications and Device Labeling, 2005-2015 - Christopher Ronk, PhD, CDRH (15)
Follicle-stimulating hormone (FSH) may exacerbate local and systemic effects of wear particles released from metal-on-metal hip implants: Implications for women - Steven C. Wood, PhD, CDRH (14)
Mechanical causes of higher hip implant failure rates in women - James Coburn, MS, CDRH (13)
Photo-Thermal Safety in Laser-based Devices for Detection and Treatment of Breast Cancer: Effect of Endogenous Absorbers and Gold Nano-Particles - Do-Hyun Kim, PhD, CDRH (13)
TREAT Registry: Women's Health Safe PCI Study: Bleeding Risk and Transradial Catheterization - Bram Zuckerman, MD, Katie O’Callaghan, Special funding/CDRH (11)
Sex-based differences in the molecular mechanisms of polymer degradation in drug eluting stents (DES) - Rallabhandi, Prasad, PhD, CDRH (11)
Evaluation of safety and effectiveness of mesh implantation in surgical interventions for the treatment of pelvic floor disorders, Phase III – Cara Krulewitch, CNM, PhD, CDRH (11)
Evaluation of Safety and Effectiveness of Mesh Implantation in Surgical Interventions for the Treatment of Pelvic Floor Disorders, PHASE II and PHASE III - Cara Krulewitch, CNM, PhD, CDRH (10)
Sex-based differences in the safety of drug-eluting stents containing bioresorbable materials - Dinesh Patwardhan, PhD, CDRH (09)
Quality of life and significant symptoms after LASIK - Malvina Eydelman, MD, CDRH (09)
The Safety and Effectiveness of Surgical Mesh Implant Use in Uro-Gynecologic Surgery for Soft Tissue Augmentation - Cara Krulewitch, CNM, PhD, CDRH (08)
Gender Differential in National Estimates for Medical Device-Associated Adverse Events (MDAEs) from Emergency Departments - Cunlin Wang, MD, PhD, CDRH (08)
Active postmarketing surveillance methods: hospital pilot - Roselie Bright, ScD, CDRH (99)
Epidemiology of medical devices in women - Danica Marinac-Dabic, MD, CDRH (97)