The Critical Responsibility of Clinical Research

The nature of science, and by extension the nature of medicine, is the ongoing, dedicated pursuit of the truth. The more we learn about the physical world and the more we apply empirical data to medicine, the better we can care for our patients.

For decades, HCA Healthcare has bolstered its status as a leader in medical research, capitalizing on the scale of the enterprise and our willingness to share assembled data to enable academic institutions and government agencies — such as the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), the Agency for Healthcare Research and Quality, and the Food and Drug Administration — to conduct large-scale studies that move the entire healthcare industry forward.

According to Kenneth Sands, MD, chief epidemiologist and chief scientific officer for the HCA Healthcare Research Institute, HCA Healthcare’s standing as the largest private hospital system in the United States positions the enterprise perfectly for many different types of research projects, from small to nationwide.

“It’s a unique advantage of the organization’s size and design and philosophy,” says Dr. Sands. “We have scale; we have centralized management; and we have this commitment to creating new knowledge. Those three elements are keys to success for large-scale clinical research.”

Research at HCA Healthcare is not a one-size-fits-all proposition. There are Graduate Medical Education research projects performed by residents and fellows, as well as interventional studies, in which HCA Healthcare works with various industry partners.

But perhaps the most effective and far-reaching studies are large-scale trials, known as cluster randomized trials, which leverage HCA Healthcare’s unparalleled reach across more than 180 hospitals and more than 2,000 points of care.

That large scale means that when best practices are not yet defined, HCA Healthcare can introduce different practices in different hospitals in a controlled manner and then compare results.

“Those kinds of studies can be difficult and can require a lot of patients, and patience,” says Dr. Sands. “HCA Healthcare is very well set up to do those kinds of studies, and it’s especially productive to do that in partnership with an academic center such as Harvard.”

Cluster randomized trials conducted by HCA Healthcare are enabling us to learn what’s best for patients as quickly as possible, which can lead to sharing new knowledge with the rest of the world.

The research process for a cluster randomized trial essentially begins once a clinical question has been identified that begs to be answered in order to advance medicine.

The interested parties — usually government agencies or academic institutions — will reach out to HCA Healthcare in order to make use of our industry-leading capabilities. To appreciate the scope and scale of one of HCA Healthcare’s cluster randomized trials, consider the swap-out trial that was recently detailed in the Journal of the American Medical Association. Commissioned by the CDC and conducted in collaboration with the Department of Population Medicine (an affiliate of Harvard Medical School), the study started in 2015 and took eight years from initiation to publication.

The trial was designed to build on previous work by Harvard and HCA Healthcare that was published in The New England Journal of Medicine in 2012 and studied the best way to prevent intensive care unit (ICU) patients from contracting methicillin-resistant Staphylococcus aureus (MRSA) in hospitals.

The question? Was the practice of using the nasal antibiotic mupirocin to prevent MRSA, a potentially lethal bacterial infection, at risk of becoming less effective. “There’s been a stewardship concern of ‘if we keep using this single antibiotic for trying to prevent MRSA, pretty soon [MRSA is] going to be resistant, and then we’re going to be left with nothing that is as effective,’” says Dr. Sands.

There was previously inadequate data to determine whether hospitals should consider swapping out mupirocin for the nasal antiseptic iodophor.

The actual trial lasted 18 months and was conducted in 137 HCA Healthcare hospitals across 18 states. Overall, the mupirocin-iodophor swap-out trial involved more than 800,000 ICU patients.

“During the study period, we found that mupirocin was in fact better and that resistance didn’t seem to matter,” reports Dr. Sands. “We were able to indicate that resistance didn’t seem to make a difference in terms of its effectiveness. Sometimes resistance can be a lab phenomenon but doesn’t actually change the ability of the antibiotic to work in the clinical sense.”

In short, the exhaustive study determined that the nasal antibiotic mupirocin reduced MRSA cultures by 18% compared to the antiseptic iodophor.

“We use the term ‘clinical differentiation.’ This allows HCA Healthcare the first opportunity to understand and implement what’s best practice for our patients,” he says. “If along the way we can provide information that allows the rest of the world to know what’s the best thing to do, we would argue that’s part of our mission.”

Just as important, says Richard Platt, MD, chair of the Department of Population Medicine at the Harvard Pilgrim Health Care Institute, a Harvard Medical School affiliate, is that the study reveals the strength of HCA Healthcare’s partnerships.

“The Institute has a major interest in helping clinicians use antibiotics in the most appropriate way,” says Dr. Platt. “HCA Healthcare’s leadership, physician providers and pharmacists in many locations have worked with our team to develop support programs that are highly effective and well received throughout the organization. We expect these will become widely adopted by other organizations.”

Clinical research being conducted at HCA Healthcare is crucial to improving care not only at our facilities, but also in medical settings everywhere.

“The questions we and HCA Healthcare address would be difficult or impossible to answer without HCA Healthcare’s commitment to best-quality care, its scale and its extraordinary ability to implement change at scale,” says Dr. Platt. “We see this commitment play out at every level of the organization. Our partnership has improved clinical outcomes for intensive care unit patients nationally.”

There is great value in adopting and distributing the best practices that come from these studies.

“It is a privilege to be advancing knowledge that otherwise would likely never get advanced,” adds Dr. Sands.

Not all research conducted at HCA Healthcare facilities has been predictable. During the COVID-19 pandemic, the enterprise’s massive collection and dissemination of data helped guide the best approaches to treating COVID-19 across the nation.

“We’ve taken care of more COVID patients than anybody else in the country,” says Dr. Sands. “Our network had to ask, ‘what is the fastest way we can make this information available to the rest of the world because it’s so important?’”

HCA Healthcare’s partnership with 12 different academic centers led to proposals for studies. The result was rapid publication of insights into best practices for COVID-19, in partnership with a variety of academicians across the nation.

One study confirmed that pulse oximetry tests, which measure the amount of oxygen (oxygen saturation) in a patient’s blood, were less accurate in people with dark skin and tended to overestimate the amount of oxygen in their systems. That’s a crucial detail, given that COVID-19 is a respiratory infection, and patients often registered low blood oxygen levels, which hamper the body’s ability to fight infection.

Collaborating with Johns Hopkins Medicine, HCA Healthcare determined via data collected through oximetry and blood gas tests that previous suspicions of inaccurate readings for dark-skinned patients were true.

“[Oximetry] was falsely reassuring in people with dark skin,” says Dr. Sands. “It meant that people did not get therapy as soon as they probably should have if they were in that category.”

The finding was substantial and was published in the summer of 2023 in the Journal of the American Medical Association.

The Lister Hospital, formerly the British Institute of Preventive Medicine, located in the Chelsea area of London, England, is an HCA Healthcare UK facility named in honor of Dr. Joseph Lister, a pioneer in aseptic surgery. Spurred by the work of legendary scientist Louis Pasteur, Dr. Lister advanced the art of antiseptic surgery at the Glasgow Royal Infirmary in Scotland.

In 1865, he became the first surgeon to operate in a chamber sterilized by dispensing antiseptic — carbolic acid — in the air. Over the following decades, there was a significant drop in patient mortality rates.

Two men influenced by Dr. Lister’s work were Robert Wood Johnson, one of three brothers who founded Johnson & Johnson, and Joseph Lawrence, MD. It was Dr. Lawrence, inspired by the work of Dr. Lister, who created a unique disinfectant for operating theaters and bathing wounds in his St. Louis, Missouri, laboratories in 1879. He called his new product Listerine, produced by the business he co-founded, Lambert Pharmacal Company.

Nearly 50 years after Dr. Lister first introduced this antiseptic into his operating room, Listerine mouthwash became the first prescription product in the United States to be sold over the counter, marketed as an oral germ killer, in 1914. Listerine, now owned by Johnson & Johnson, has been subjected to numerous clinical trials and is recognized for helping prevent plaque deposition and gingival inflammation. Today, the 57-bed Lister Hospital in London continues the doctor’s work.