PROVIDENCE – The recent push to speed the development of a vaccine for COVID-19 has translated into more public awareness about clinical trials, normally the arcane venue of researchers, biotech entrepreneurs and pharmaceutical companies.

In normal times, the process of clinical trials is a scientific approach to test the efficacy and the safety of potential therapeutics and vaccines, meeting rigorous standards of the U.S. Food and Drug Administration before receiving approval, a process that can sometimes take years.

These, however, are not normal times, when it comes to the efforts to create an effective vaccine for the novel coronavirus, with pharmaceutical companies competing in the high-stakes enterprise to develop a successful approach, with different governments entering into contracts to speed the research and production of potential vaccines and therapeutics.

While there are a number of potential vaccines in the pipeline, not all will prove to be successful – and the approaches being taken differ widely.

At the same time, there are a range of clinical trials now underway here in Rhode Island, including a new Phase III clinical global study of a treatment aimed at preventing cognitive decline in people with preclinical Alzheimer’s Disease, with Butler Hospital’s Memory and Aging Program serving as one of the U.S. sites to screen potential participants.

That clinical study is a double blind, randomized study, open to individuals between the ages of 55 to 80, who are cognitively normal but have either elevated or intermediate levels of amyloid beta protein in the brain. Some 1,400 participants will be enrolled and treated with drug, known as BAN2401, for 216 weeks – or four years.

Translated, most clinical studies are exercises in patience and persistence – and dogged scientific pursuit, contrary to the current push for “immediate gratification” with vaccines and therapeutics for COVID-19.

A recent story pitch caught ConvergenceRI’s eye regarding the relative success of the Women and Infants Hospital Gynecologic Oncology Group, which is now the number-one group in the nation among 125 member institutions who are part of the National Cancer Institute’s National Clinical Trial Network, with the highest participation of patients in clinical trials between January and June of 2020.

In a time of pandemic, when much of the ongoing work of the health care delivery system has been disrupted, the capability of maintaining a high degree of participation in clinical studies seemed a worthy story to pursue.

Here is the ConvergenceRI interview with Dr. Paul A. DiSilvestro, director of the Program in Women’s Oncology and the Division of Gynecologic Oncology, and the ways that clinical trials offer patients cutting-edge treatment options, even in the midst of pandemic.

ConvergenceRI: What does it mean, in terms of outcomes, that the Women and Infants Gyn Oncology group has the highest rate of participation of patients in clinical trials in the nation for Main Members of the National Clinical Trial Network?
DiSILVESTRO: This is a difficult question to answer directly. Our participation affords our patients access to clinical trials, and most literature would support the fact that cancer patients in clinical trials have an improved outcome versus those not enrolled.

From a global perspective, the faster we can enroll and complete trials means we know sooner whether a new treatment is beneficial and can bring those improvements to our patients.

ConvergenceRI: How many clinical trials are being conducted in Rhode Island at Women and Infants Hospital under the direction of the WIH Gyn Oncology Group? Can you describe some of them?
DiSILVESTRO: We have anywhere from 20 to 40 trials open at any one time. Examples of these trials include early drug development, i.e., the use of new interventions in what are called Phase I trials.

One example of a Phase 1 trial is NRG GY017, which is evaluating the role of the addition of immunotherapy to frontline cervix cancer treatment.

An example of a larger trial would be NRG GY021, which is investigating the addition of a form of immunotherapy to PARP inhibition in recurrent ovarian cancer.

ConvergenceRI: How has the coronavirus pandemic impacted the capability to maintain ongoing contact with patients? Has there been a significant move to telehealth platforms?
DiSILVESTRO: The coronavirus has impacted some of our trials where perhaps the primary question was not one of the benefits of a new treatment.

In those trials, the risk of coming to the hospital and potentially having a COVID-19 exposure outweighs the benefit of the knowledge we would gain [a scenario which has not occurred at our institution, fortunately]. Otherwise, our treatment trials have continued without interruption.

We have used telehealth more frequently, and the National Cancer Institute did change some mandates about how research is conducted to help with conditions caused by the pandemic.

ConvergenceRI: What kind of ongoing research being conducted in Rhode Island has contributed to the clinical trials now underway? Can you describe the pathway, often long and convoluted, in terms of science and funding, that it takes to get to the clinical trial stage?
DiSILVESTRO: Generally, this is a by-product of participating in early phase research. An example of this was the participation in GOG 9923, which evaluated the addition of a drug called Veliparib to standard therapy in ovarian cancer.

Our institution enrolled approximately 50 patients in this early phase study. The results of this study were then used to design a Phase 3 confirmatory study using this drug, in which we again participated, which ultimately demonstrated that adding this drug to standard therapy improved survival outcomes.

Women and Infants Hospital investigators were authors on both of these publications. This type of pathway probably took nearly ten years from start to finish.

ConvergenceRI: As part of the clinical trials, are there databases being built around potential environmental relationships to exposure to toxic chemicals? For instance, bladder cancer had a high rate of incidence in Rhode Island, which some epidemiologists viewed as potentially being linked to the jewelry and plating industry in Rhode Island?
DiSILVESTRO: Most of our clinical trials do query the patients regarding multiple aspects of their lives, including demographic and quality of life data, to better understand not only the benefit of the treatment, but also its impact on the quality of life of the patient.

ConvergenceRI: How have advances in being able to conduct analyses of the genome of different cancers improved the kinds of potential therapeutic treatments?
DiSILVESTRO: This is fundamentally defined by whether a cancer has a targetable mutation within its genome, or genetic makeup. A classic example of this is the presence of a BRCA mutation in a woman with ovarian cancer. The success of the PARP inhibitor class of drugs, which targets a susceptible DNA repair process in BRCA patients, works best in that population of patients.

ConvergenceRI: As part of the protocols for care for participants in these clinical trials, are their practices around patient care related to managing stress levels [allostatic load] that are part of the treatments?
DiSILVESTRO: We have always considered clinical trials to be an integral part of clinical care and not a separate process. Those patients being treated on a trial and those being treated with standard strategies are cared for in the same multidisciplinary and supportive manner, including regular supportive work with our social work team.

Probably the most important thing to recognize from an additional stress perspective is some of the additional testing that may be part of a trial. That is why the informed consent process puts a great deal of emphasis on study design and knowledge of the additional work that may be involved so patients are not surprised.