Olivia Barnes, Senior Research Nurse at Sherbourne Medical Centre in Leamington Spa, discusses how COVID-19 is impacting the clinical trials she is working on.
Selections from Coronavirus Diaries: April–July 2020
Olivia Barnes is a Senior Research Nurse at Sherbourne Medical Centre in Leamington Spa. In this series of weekly posts she discusses how COVID-19 is impacting the clinical trials she is working on, as well as her work on studies in response to the virus.
Conducting COVID-19 clinical studies: 7 April 2020
Everything changed a couple of days ago when we got two COVID-19 studies and I'm now frantically working to get those set up. They are both RCGP (Royal College of General Practitioners) studies; one is on test kits where patients with symptoms of COVID-19, and the other is a randomized study for an anti-malarial for the over 50s. Both are entirely remote; for the testing, the patient will give verbal consent and then self-test, and for the randomized study, the patient gives an eConsent and completes their eligibility online. The only thing that has to leave the surgery is the drugs and the test kits.
I can't believe the speed that they’ve been set up. Instead of things following a nice linear program, everybody's having to work very, very differently and things that you expect in a certain time frame has totally changed. The speed at which they've been set up is very impressive - the randomized trial has been put together in days and weeks rather than months.
Looking to the future I would hope that this speed is going to continue with other studies. I think the UK has lagged behind, and despite the best efforts of the NIHR, it still seems to take an inordinate amount of time to get things up and running.
We are a small research department, there is only three of us - the Principal Investigator, myself and site coordinator, so one could drop out due to illness or self isolation, but if two dropped out it would be a bit dire. I work three days a week, but I'm quite prepared to come in the other days to get these two very important studies done.
"The speed at which they've been set up is very impressive - the randomized trial has been put together in days and weeks rather than months."
Protocol deviation in clinical trials during COVID-19: 15 April 2020
For everyone, we all feel in a state of suspended animation. It is personally very strange that I'm still coming to work and the roads are empty. It just all adds to the strangeness really.
The main thing that has been on my mind this week is protocol deviations. It's something we try our absolute hardest never to have normally, and yet the minute they are coming thick and fast. Things that are meant to be done in person, such as blood pressures, taking temperatures and the doctor listening to their chest - all that can't be. So we have a detailed telephone call and listen to what the patient is telling us without doing the physical checks that the protocol sets out.
When I'm sat down doing my paperwork, it doesn't sit very well with me, as it is something we strive very hard to avoid usually. Research is very black and white, so you've got to get it right and get it right first time. With any protocol deviations you must make sure you document everything very, very carefully to show that you are aware of the deviation and why it occurred.
We obviously want good data, and we want to do everything we possibly can in the studies, but at the end of the day, it's the patients’ safety that overrides everything.
COVID-19 testing study
For our study on COVID-19 testing, unfortunately the people who may have been eligible have had their symptoms for too long, so weren't eligible. The patient has to have a temperature and a cough, but the swabbing test must be taken within seven days of the first symptom.
So as soon as the doctor is happy they are eligible, I would get the test kit to the patient. I will either ask someone who does not live with the patient to collect the kit from the surgery and then post or if that is not possible I could take the kit to the patient myself and wait for them to take the swab, then take it straight to the Post Office.
COVID-19 anti-malarial study
We sent out over 2000 text messages this morning (Tuesday 14 April) for a randomized study for an anti-malarial drug as treatment for COVID-19 for the over 50s. It's the first time ever that I've sent out that many text messages so I really don't know what to expect. I've got enough medication for 16 patients, so that would be 32 in the study given that it is a 50-50 randomised trial, and if I get those, I can order more.
Anyone who wants to take part should reply with an email straight to the study centre, but in my past experience most people will still phone here to find out more because the texts are coming from us. The process is all done online; everything from consent to the daily questionnaires, so unfortunately if they don't have access to the internet they won't be able to take part.
"For everyone, we all feel in a state of suspended animation. It is personally very strange that I'm still coming to work and the roads are empty. It just all adds to the strangeness really."
COVID-19 immunity serology testing study: 29 April 2020
Last week we sent two thousand text messages for the anti-malarial drug COVID-19 study – it is a 50/50 randomized split between those taking the drug and self-testing, and those just self-testing. Within a day we had two ladies who contacted the help desk and were eligible. One was allocated to the drug and one just to swabbing. We actually dropped the drugs and kits off to them because we were be able to do that on our way home, though the NIHR are co-ordinating courier services if we need them. It is always the first patients in any study when you find glitches, but all went reasonably well. It will be interesting to see the result, which will take about a week to come back.
And on the self-testing study we have had three patients and the first two came back negative. However, we haven't had any recruits this week so far for either study.
The study that we have had the best results on is one on serology testing, from the RCGP via Oxford University. It is for patients who had to be attending the surgery for a blood test – we couldn't approach anybody else other than people already having booked for a blood test here at the surgery. They have been given a one page patient information sheet and asked if they mind having an extra tube of blood taken for this research. The patients won’t get results and we won’t get results – it is purely to look at background immunity in the general population.
Of the first 26 patients to come into the surgery, 25 agreed to take part and I've had to order another 50 kits. This could not have happened without the help of our surgery HCA who sees all the patients for blood tests. In addition to her own work, she has helped with this project, taking verbal consent, labelling the samples and even taking the kits to the post office at the end of her shift.
People are quite happy to help the NHS and are quite altruistic - it's a lovely thing to see. I see it in my normal working day - we do a lot of research here at Sherbourne and our patients are very aware of that – and in general we don't have a problem getting volunteers even for a Phase II or early Phase III studies.
I’m also having to do some education myself around COVID-19 so I can help patients with background information. The World Health Organization has a really good page showing the difference between the serology testing - what they're trying to do and what tests are available.
The new normal way of working: 13 May 2020
We’ve now settled into a bit of a pattern - I don't like to use the old cliché, but it seems to be we now have a ‘new normal’ and a bit of a routine.
Every Monday I send an email to all clinical staff - and in fact at the minute it's everybody in the practice because the whole practice needs to be on board when you're doing research like this – to tell them what studies we’re doing and what numbers we've got, to keep it at the front of their mind. Obviously, I’m reliant on the partners or reception, who are taking the telephone calls, to then pass the patients’ details on to me.
Luckily very few of our staff have been off sick. We have quite a strict regime around opening the door and what the reception staff wear, and we have a very good cleaning regime after we've used our desks. Even our coffee breaks have been as per the social distancing guidelines. When patients come into the surgery, they ring a bell and then they come in one at a time. Very, very seldom is there anybody actually in the waiting room because they just come in as their appointment is due.
We were lucky, as we’ve been doing telephone triage for over a year, but I do know a lot of GP surgeries who weren't doing that have struggled. It takes a while to settle into it as it is a very, very different way of working for everybody – the reception staff, the patient and the doctor.
Study updates: 16 June 2020
We’ve been told studies may restart soon, but nothing as of yet has begun. However, we have had our first patient on a study back in the building. He’s been in the study for a year and there were a lot of bloods to be taken, so from a study point of view, it was in the patient’s interest to come in. We asked if he would be willing to come to the practice and he was, but if the patient hadn’t of been happy, we would obviously have done the visit over the phone. The study team had made allowances and the advice was that if we could get the patient back in within a month of the planned visit to do the bloods, that would still be acceptable.
We had to see him wearing full PPE and then there was a lot of cleaning afterwards. In the past we had a dedicated research room with everything we needed, whereas now we’re only using two rooms to see patients in. So I have to do a bit more planning to make sure I take all my research equipment I need down to the room with me, so that once we were in, we didn’t have to come in and out. It is a very different way of working, but we have two more patients coming in next week and I’m going to ask them how they feel about being in a study during COVID-19.
With our COVID-19 studies, we’re continuing with the serology study and we now have 130 taking part in that and I’ve just ordered more kits. The anti-malarial treatment study we were taking part in has been replaced by the antibiotic Azithromycin. It remains a two-armed study with all patients being tested, but 50% will now get Azithromycin instead of the anti-malarial drug.
However, the other COVID-19 studies have been very quiet, with no new recruits. It is obviously great that there are far fewer cases of COVID-19 now, but from a research point of view I don’t know if they have enough numbers or not to be viable. Hindsight is a wonderful thing, but if something could have been set up with the 111 service that may have worked better to direct patients to us, but they were so inundated with calls.
Thinking outside the box to restart clinical trials with COVID-19 restrictions: 10 July 2020
Things have been much busier in the last few weeks, as one of the studies that was on hold has restarted. It is an observational study, following patients for a year for cardiovascular events.
For this study, obviously they've had to make amendments to do things by post. Questionnaires were either posted or emailed, and after the patient consents, they post it back for the Principal Investigator to check everything, counter-sign the consent, and then post it back out. So it is an awful lot of extra work. The patient doesn't have to come in at any time. They would have come in for a baseline visit and I would have tested blood pressure, weight and so on, whereas now there is an amendment to take the latest blood pressure and weight, as long as it is within a set timeframe. So it has been quite a challenge changing how we would have run it, but it's working - our target was ten, we've approached eight people so far and had four consent.
Hopefully some of the other studies will start again soon - lots of the Sponsors are tentatively asking how things are at the site and how prepared we are. We have got lots of guidelines from NHS England and are following an SOP from them, but for us it is the patients having the faith in us to be willing to come in and see us that is most important. Give it another month and I think we will be significantly busier.
We're still continuing with the COVID-19 serology testing study and people are still willing to give blood samples for research purposes. We're also going to send out another text message for the principal study we are working on to update patients that the study has changed from an anti-malarial treatment to the antibiotic Azithromycin. With COVID-19 incidents going down nationally, they are not getting the numbers for the study.
We've been approached about a COVID-19 vaccine study, but with restrictions in place, we're not sure how that will work, so we're going to have to think a bit more out of the box. With vaccine studies you're looking at large numbers of patients, regular visits, and patients having to stay in the surgery for significant time after first dosing, so it is going to be very challenging. We're keen to do the study, but logistically we don't know how it is going to work - we're going to have to think very differently in ways we've never considered before.
To find out more about the studies, visit the Sherbourne Medical Centre website.
Today’s transformations for COVID-19 are tomorrow’s standards
Never, in the history of healthcare, have so many organizations come together to collaborate that will evolve clinical trials today and for the future.
Today’s transformations for COVID-19 are tomorrow’s standards
By Chad Clark, President, Precision for Medicine
On March 11, 2020, when the World Health Organization (WHO) declared SARS-CoV2 (COVID-19) a global pandemic, many of the conventional ways of conducting clinical trials were quickly and judiciously reviewed and reworked to address the crisis at hand. Never, in the history of healthcare, have so many organizations come together to collaborate and create solutions that will inform and evolve clinical trials today and for the future.
In response to the COVID-19 emergency, clinical trial research assessing the efficacy and safety of clinical candidate interventions to treat the virus are emerging at an exceptional rate. As of early May, over 800 clinical trials have been registered at various national and international clinical trial registry sites.
As the industry and regulators band together in a race for a vaccine and viable therapeutic solutions for COVID-19, we find ourselves in an unprecedented position to accelerate trial timelines, as well as regulatory approvals. In addition to supporting the fight against COVID-19, we are all tasked with continuing the over 50,000 active clinical trials in 25 condition categories that existed before COVID-19. This unique intersection of working differently to stop COVID-19 and continuing life-saving clinical trials at risk due to limited access to sites and patients, has finally solidified more novel approaches to executing clinical trials that can ensure safety and quality, reduce cost and increase access to patients.
"These times have finally forced us to confront the need to redefine how we conduct trials.."
It is unfortunate that it took a pandemic for this to happen. As an industry we have shied away from risk, holding fast to the tried and true methodologies and processes of clinical trials. But these times have finally forced us to confront the need to redefine how we conduct trials. In the past few months, both the industry and regulators have been extremely thoughtful, flexible, and creative in adapting protocols and applying ideas and technologies that, until now, have been underutilized.
Governments and Regulators have led the way to encourage open collaboration. The Food and Drug Administration’s (FDA) latest initiative and most transformational program, the coronavirus treatment acceleration program (CTAP) creates access and feedback for innovators in a variety of forms – PowerPoints, concept papers for therapies, while providing substantive responses within 24 hours. This transformational program reduces reliance on legacy processes such as pre-investigational new drug (IND) meetings only to find out weeks, or even months later there are gaps in data or strategies. The FDA is engaging in real-time to help companies think through their COVID-19 clinical trials.
In the UK, the National Health Services has created a patient pathway program. Through a hotline, patients take a survey to have their condition classified and are triaged to specific hospitals equipped to manage specific patient populations. The information is also used by sponsors to determine the best sites to host particular studies, and in many cases, patient informed consent can be provided verbally to reduce exposures that can then transmit the virus.
Creating an open and transparent environment so that governments, regulators, and researchers can work together to streamline protocols and processes, while maintaining the integrity of the trial data, is only part of the equation. As social distancing is being enforced around the world, researchers are adopting a risk-based approach that incorporates remote patient monitoring, telemedicine visits, wearables and improved access to electronic health records to enhance patient safety, while reducing site burden.
Since rare disease trials have faced many of the same challenges being posed by the coronavirus, Precision for Medicine has been actively engaging these tools for years as we help innovators develop therapeutic and diagnostic solutions. These changes are not only necessary for COVID-19 treatment development but, as the industry has long recognized, we need to expand patient populations participating in clinical trials for many drugs under development.
The current effects of the novel coronavirus have made an indelible impact on the world with large-scale and long-lasting challenges that have forced us to adapt and innovate in ways we could not have imagined just months ago. Creative trial designs such as master-trials, use of wearables, home-health and integrated EHR to EDC technology solutions all will now be the norm as we focus on ensuring safety, maintaining quality, reducing costs and accelerating timelines while creating access to patients in need. We must seize this opportunity to make today’s transformational changes tomorrow’s standards.
ABOUT THE AUTHOR: Chad Clark, President, Precision for Medicine, is recognized as an industry leader focused on combining cutting-edge technology, strategic program design, and operational excellence to help life sciences companies effectively address the increasing evidence demands and need to accelerate research initiatives. Previous experience spans the execution of phase 1–4 clinical trials, specialty lab services, biospecimen logistics and banking, risk management, and patient support initiatives
Conducting clinical trials during COVID-19
Three industry insiders offer insights into their experience
Conducting clinical trials during COVID-19
COVID-19 has affected all aspects of life and clinical trials are no exception. How have teams decentralized so quickly while keeping research on track? How have researchers incorporated regulatory changes and new guidance? We asked three industry professionals for their insight into strategies being used to manage workload and keep clinical research timely during this time of great uncertainty.
Bodo Lutz, Clinical Risk Management and Data Integrity QA, Novartis Global Development Quality
The sense is we weren’t as prepared as we all thought – how did your team decentralize so quickly while keeping research on track?
"Having performed decentralized trials prior to the COVID-19 pandemic we used this expertise and already contracted service providers to shift trials from traditional to (partly) remote operating model, successfully."
What regulatory changes/guidance have been released/adjusted globally and how are researchers incorporating them?
"As countries were impacted by COVID-19 with different severity and at different time periods, relevant health authorities published guidelines at different stages of COVID-19. Global trials needed to be adapted following country specific requirements.
Some of the guidelines have not considered all aspects of possible remote trial settings which could have been implemented by the Sponsors, for example, Home Nursing, to minimize a patient’s exposure to COVID-19 while continuing with patient treatment and ensuring patient safety.
The change of trial settings to a remote approach was linked to the need of each individual trial depending on, for example, the pandemic situation, risk assessment outcome, patient treatment, and patients’ health conditions."
What are some lessons learned from this process?
"We will work to be prepared for a potential second COVID-19 wave. Congresses like Clinical Trials Europe will enable Sponsors, Service Providers and Patient Advocacy Groups to share experiences, challenges and potential solutions."
Abby Sener, Manager, Almac ONE
What regulatory changes/guidance have been released/adjusted globally and how are researchers incorporating them?
"Both the MHRA and FDA released COVID guidance on documenting deviations to protocols and/or established procedures. Almac was able to leverage this guidance to inform our business strategies and solutions, as well as incorporate this when we were approached by various sponsors to assist with managing the impact of the pandemic on their ongoing and future trials. Many sponsors were (and are still) seeking alternative, sometimes unconventional, ways of supplying clinical material to patients due to either patient inability to travel or the site closures.
We closely examined the various Privacy Regulations and Standards and compared these to our contractual agreements to determine what solutions were possible to support from a system perspective. Now, we continue to see clients focusing on advanced planning for future impact from the pandemic, investigating options such as including direct to patient distribution into protocol design and study requirements up front."
Trellis Usher, Founder & CEO, Nova Health Labs
What has been implemented in your team that has been a huge success?
"Our team was used to working remotely when the pandemic hit but we weren’t very efficient at it. We could count on our in-person meetings to catch up. Post-COVID, we had to be very intentional about doing a few things to help keep us on track:
- Stood up a team collaboration site
- Clear accountability on roles and responsibilities
- Defined timeline for tasks and milestones
- Standing weekly update meetings with agenda
- Weekly “team office hours” where we were all available and could jump on a call or virtual meeting if needed (not Monday or Friday)
How can we think about conducting clinical trials during the time of COVID-19?
"Our software platform uses voice technology (think Alexa and Siri) and voicemails to triage practice communications. One of the things we are looking to explore but haven’t run a pilot on yet is how can this technology be used to help gather PRO for clinical trials. Our position is that our software can automate the collection of patient reported outcomes from patients participating in trials while offering them a frictionless experience:
- The trial participant will set up a profile on our mobile app. We can work with the trial sponsor to set them all up in a single batch so the patients don’t have to worry with that initial step.
- The trial participant gets a call from to authenticate their identity and confirm they are in a specific trial and phase.
- On a set frequency (daily, weekly, monthly), participant receives a call with pre-set questions and can answer them just as if they were having a phone conversation.
- Information and data are automatically transcribed, compiled and sent to trial manager or sponsor for analysis. Nova can also do some basic analysis.
Participants will then be reminded of site visit dates, times and locations via voicemail, email or text."