Dot Laboratories, Inc. (“DotLab”) recently announced the initiation of EMPOWER, a groundbreaking clinical study for a non-invasive (e.g. blood) test to aid in the diagnosis of endometriosis.
The EMPOWER Study is the first of its kind and one of the largest efforts ever conducted to develop a non-invasive diagnostic test for endometriosis, a disease that impacts an estimated 200 million female-born people worldwide. The study is enrolling patients having surgery for suspicion of endometriosis or other benign gynecological conditions and collects extensive clinical history along with blood and saliva samples for independent validation in different specimen types. The samples and associated data will be used to develop DotEndo™, DotLab’s non-invasive test for endometriosis.
Here, we elaborate on why the initiation of a study conducted with the rigor and robustness of EMPOWER is a significant advancement in women’s healthcare.
Endometriosis is a chronic and progressive disease for which earlier disease identification and management can prevent long-term complications that reduce quality of life. Patients living with endometriosis may endure significant pain (especially at the time of menstruation), reduced fertility, increased hospitalizations, and a poorer quality of life.
Diagnostic delay is a significant hurdle to timely management of the disease. It can often take up to a decade and referrals to numerous specialists before receiving a definitive diagnosis and treatment plan. The lack of a non-invasive diagnostic tool is a meaningful contributor to this problem.
When developing a new diagnostic test, the studies to develop and evaluate the test must adequately represent the target population, in order to ensure the study results will be generalizable. This process requires representation of diverse populations in the sample sets.
Diversity in clinical studies has been a long-standing problem. For example, in 2013, dosage instructions had to be revised for females after instances of impairment for females who used the sleeping medication, Ambien, with the prescribed dosage. The underlying issue: females had not been sufficiently represented in dosing studies.
Diverse recruiting is particularly important with endometriosis studies, because endometriosis is a very heterogeneous disease, meaning that the underlying biology of one person’s endometriosis may be very different from another person’s.
The EMPOWER Study stands out because surgical confirmation of active endometriosis is obtained by premier surgeons in the country within weeks of the study blood and saliva samples. Today, the diagnosis of endometriosis can only be established through laparoscopic surgery - which is the standard of care for diagnosis - by surgeons highly-skilled at identifying endometriosis. Surgical confirmation of the presence or absence of endometriosis for all of the participant samples used for test development and validation is important because the symptoms of endometriosis are shared with many other conditions, and it can be difficult to distinguish endometriosis from those other conditions based on clinical factors alone. Additionally, endometriosis is not a steady state disease, and the presence and severity can change over time, making the timing between correlation of surgical confirmation and sample collection an important factor.
Because of the challenges and complexities of a study that only enrolls participants scheduled for upcoming surgery, other studies developing and evaluating endometriosis diagnostics have included participants with a self-reported or clinical diagnosis but without surgical confirmation, or alternatively, a large gap of time between surgical confirmation and study sample collection. Including only samples collected in women with impending surgery distinguishes EMPOWER from other clinical studies.
To develop a test to aid in the diagnosis of endometriosis, such as DotEndo, patterns of biomarker signatures are compared between a group of participants with endometriosis and a group without endometriosis. Meaningful differences in signatures between the two cohorts are then used to create a model that the test uses to distinguish endometriosis from non-endometriosis. If the development of the test (model) is based off of incorrect assumptions (i.e. patients without endometriosis are included in the endometriosis group - or vice versa - which can happen if the diagnosis of endometriosis is not made based on recent surgery) the accuracy of the test may be impacted and it could be unreliable.
“The symptoms of endometriosis are similar to those of other gynecological conditions, making it challenging to diagnose based solely on clinical factors,” said the study’s principal investigator Robert Taylor MD, PhD, Professor in the Department of Obstetrics and Gynecology and Assistant Dean and Director of the MD-PhD Program at University at Buffalo. “A surgical diagnosis associated with samples used in test development is of paramount importance to ensuring the accuracy of the test.”
A limitation of many diagnostic tests is that they have been developed based on participant samples from a single or handful of centers that may not be representative of the broader population. The EMPOWER Study, on the other hand, will enroll 1,000 participants at centers across the US. This multi-center approach increases the representation of diverse populations in the study, especially ethnic groups that are well represented in some parts of the US, but not others.
EMPOWER is collecting uniquely thorough clinical data (e.g. medication, symptoms) covering years of history. This robust clinical data allows the study team to ensure that the study population is representative of females with various symptomatologies, disease severities, comorbidities, and treatment histories.
In summary, the EMPOWER Study is the most robust study to be conducted for the development of a non-invasive test for endometriosis. EMPOWER is designed to instill confidence in healthcare stakeholders and patients that DotEndo was developed with significant and unprecedented scientific rigor.
Image Credit: Tabitha Tuner