UPDATE: March 19, 2019: A panel of microbiology device experts made recommendations on aspects of high risk HPV screening devices when it convened earlier this month, such as how to best bolster clinical studies, optimally define tests’ indications, and appropriately assess safety and effectiveness of new tests, the details of which are laid out in an advisory committee meeting summary posted by FDA this week.
To improve breadth and diversity of patient populations in clinical studies, panelists recommended reaching out to women with a range of screening and vaccination backgrounds. Other strategies included carefully considering incorporating archived specimens for study and allowing study enrollment from referral clinics.
Panelists concurred that in defining devices’ recommended indications, a more generic statement encompassing a general screening population was appropriate, and that the statement should not necessarily include strict, specific medical practice guidelines, in light of the quickly evolving nature of the devices.
In assessing safety and effectiveness of new devices, the experts had concerns with the sole adoption of a molecular composite comparator method, but agreed evaluation of relative performance against a clinical endpoint comparator was appropriate.
Five years after FDA's Microbiology Devices Advisory Committee voted to widen the indication for a Roche test that screens for the most significant cancer-causing strains of human papilloma virus, the panel is set to meet again to discuss innovation within screening devices for high-risk (HR) HPV.
Materials released by FDA ahead of a Friday, March 8 meeting indicated experts will be asked to consider five main questions relating to clinical study design and endpoints, colposcopy referral protocol in clinical studies, and tests' indications for use and the data analyses used to support them, all with the aim of informing how future PMA applications for HR HPV devices are reviewed.
FDA said now is an appropriate time to reconsider approaches to the Class III HR HPV devices due to better understanding of cervical carcinogenesis and a changing screening population caused by HPV vaccine uptake, as well as continuously evolving screening and patient guidelines.
High-risk human papilloma virus is considered any strain that can cause cervical and other cancers, according to the National Cancer Institute. Of the more than 200 related strains of HPV, about 14 are considered high risk, with two known as HPV16 and HPV18 responsible for most HPV-related cancers.
While HPV is the most common sexually transmitted infection in the U.S. and does not typically result in cancer, when HR HPV is unsuccessfully controlled by the immune system for years on end, cells can grow cancerous. Guidance issued as recently as September 2018 by the United States Preventative Services Task Force recommends primary HPV screening or HPV/cytology co-testing every five years for women between the ages of 30 and 65.
FDA notes that the first HR HPV device for use in routine cervical cancer screening was approved by the agency in 2003. Shortly thereafter in 2006, FDA approved Merck’s Gardasil vaccine for females ages 9 to 26.
Almost five years ago to the day, a Microbiology Devices panel discussed a PMA supplement for expanded indication of Roche’s cobas HPV test, which screens for HPV16 and HPV18. The vote allowed the test to be used as a first-line primary cervical cancer screening test, meaning patient management could be driven primarily by the HR HPV test results, as opposed to merely being an adjunct to cytology. In addition to the Roche test, there are FDA-approved screens on the market from Hologic and BD with varying indications.
"Decreases in HR HPV positivity rates due to HPV vaccination and additional research have created a setting for HR HPV testing that is different from when the first generation of HR HPV devices were approved. The long term predictive values of HR HPV tests and regression rates of cervical dysplasia, as well as other important clinical predictors, are now known from over a decade of research involving HPV devices in clinical practice," FDA laid out in a pre-meeting briefing.
"We believe the accumulated knowledge over the past 16 years, against the background of changing prevalence, could support innovation in the methods used in the development and evaluation of HR HPV devices," FDA added.
Friday's meeting is just the first of a handful of CDRH advisory committee assemblies this month, with the Neurological Devices Committee set to meet March 21 regarding a PMA application of a neurostimulation device for use in patients with Alzheimer’s and dementia, and the General and Plastic Surgery Devices Committee to convene March 25-26 regarding the benefit-risk profile of breast implants.