Southampton Academy of Research

Dr Sophie Fletcher is a Consultant Respiratory Physician at University Hospital Southampton (UHS) and holder of a Research Leaders Programme (RLP) fellowship.

Her research focuses on improving our understanding and treatment of fibrotic lung disease, but she is also the local lead at UHS for the world’s largest COVID-19 trial.

Giving her patients the ‘full menu’ of options

Fibrotic lung diseases are a group of rare diseases. Patients with these conditions experience shortness of breath that gets worse over time, to the point that they may need oxygen.

The most common of these conditions is idiopathic pulmonary fibrosis (IPF). People diagnosed with this condition only have a life expectancy of 3-5 years from diagnosis.

There are currently only two treatment options – the anti-fibrotic drugs pirfenidone and nintedanib. Both are expensive and can only be prescribed by a specialist centre like UHS, which is one of only around 12 specialist centres for the disease in the UK.

“If we’re not part of research for these patients, they have limited options,” says Sophie. “There are criteria the patients have to meet to gain these drugs, and if they don’t meet those criteria, they have no other options. So the only other option they may have is research.”

Patients taking part in a clinical trial get access to other novel antifibrotic drugs for free. In many cases, if the trial is successful, an agreement with the pharmaceutical company allows this free access to continue after the trial has finished on compassionate grounds.

She explains it to her patients as being the difference between having just the first page of a menu to choose from (drugs available on the NHS), and the full menu (with additional research options).

“That’s been the principal reason why I’ve been doing research all these years – to provide patients with an option who otherwise wouldn’t have one.”

Seeing the value of research

Sophie first joined UHS as a consultant in 2013. When she joined, she became involved in research trials into fibrotic lung disease, her specialist area of interest.

In this year, the anti-fibrotic drug pirfenidone became available on the NHS as the first treatment for patients with fibrotic lung disease. As she’d been involved in the clinical trials that led up to this point, she was already familiar with it.

In 2014, she had a similar experience with the drug nintedanib. She has continued to conduct late-stage trials of treatments for patients ever since. This has mostly been with commercial companies, as these trials need large groups of patients and are expensive to run.

“I could see the value of being involved in clinical trial,” Sophie says, “because if you’re involved before the drug gets released, you’re already familiar and have some level of expertise that you can translate to your patient community as soon as the NHS gets involved.”

Leading COVID-19 research at UHS

At the beginning of the COVID-19 pandemic, Sophie took on the role of principal investigator (PI) at UHS for the RECOVERY trial - the world’s largest clinical trial into treatments for COVID-19.

“It is the biggest trial in COVID-19 globally, and it’s beyond influential,” says Sophie. “It’s become standard practice.”

At the time, in March 2020, almost nothing was known about the disease and how best to treat it.

“You can’t go to a textbook,” she says. “It’s like you open a textbook and there’s a blank page, there’s nothing there. So you have to go back to first principles.”

She says one of the main reasons the RECOVERY trial was so successful was the “brave decision” made by the NHS. No doctors were allowed to prescribe any drugs to COVID-19 patients, except as part of a clinical trial. This meant the uptake to the trial was huge, and the results came in fast.

“If the drug worked, we knew about it,” she explains, “and if the drug didn’t work, we knew about it. Then we quickly stopped using it and moved on to something else.”

Another reason for the trial’s success has been its simplicity. Most trial protocols are lengthy, complicated documents, but RECOVERY’s is only two sides of A4. The only criteria for taking part are being over the age of 18, in hospital with COVID-19.

The drugs chosen for the trial, at least initially, were ones that doctors were already familiar with and had in the cupboard. This meant that when drugs were successful, they could be rolled out incredibly fast. Sophie thinks back to the first one they found, the steroid dexamethasone.

“I remember that day,” she reflects. “I remember sitting in a meeting and the results came through, and we were prescribing it as standard-of-care that evening.”

The trial, which is still running, has since discovered many more treatments for COVID-19 hospital patients and provided evidence showing many others are not effective.

Inspiring others

One of Sophie’s main reasons for applying for an RLP fellowship is to use her experience and knowledge to inspire other clinicians to follow in her footsteps. She knows the challenges, not least is the need to start out doing unpaid research in your spare time, alongside a full-time clinical job.

“Doing research when you’re a clinician is difficult,” she says. “Although I say I’ve been involved in research, it’s mainly been through my own passion and stubbornness.”

Sophie hopes the fellowship will give her the time to expand her current research portfolio, so she can help develop more treatments for her patients. She also hopes it will give her the authority to speak up, ask questions, and call for changes that could make research better for everyone.