Independent Medical Writer Leonie Onslow explores the challenges of traditional clinical trial models and how to improve recruitment and retention.
Covid-19 and the subsequent strain on health systems and research capabilities has created the opportunity to change the traditional clinical trial model of using hundreds of GP sites, which in the long term has proven to be expensive and very slow. If that change doesn’t happen, further delays in access to new, potentially life-changing medicines can be expected.
“Post-Covid-19, we’ve got a backlog of normal research, but we also have a massive backlog of patients,” says James Brook, Regional Head of Europe, Middle East, and Africa at contract research company, Tigermed Group. This is detracting from research efforts and contributing to delays in getting innovative medical products to the patients that need them most.
According to the British Medical Association, as of September 2022, close to 7.1 million people were waiting for medical treatment; a record high. Brook believes it will take two years to clear this backlog of patients. In the meantime, health systems and staff are under immense strain, leaving little time to conduct and contribute to research efforts.
Historically, sponsors have sourced patients through a network of doctors enrolling patients on an opportunistic basis. This can be a long process, depending on which patients walk through a doctor’s doors, whether any of them fit the trial protocol, and crucially whether the doctor remembers to share information on the trial.
Data disclosed by big pharma shows that around 50% of GP clinical trial sites only recruit one patient or less. In this scenario, recruiting one patient is actually the worst possible outcome, as that single site then has to be monitored for the duration of the trial. In large Phase III trials with thousands of patients involved this can mean that hundreds of sites have to be opened and monitored.
Each site opening costs the sponsor in excess of $50,000 in selection, inspection, training and monitoring costs regardless of the site’s performance.
This poor patient recruitment model is now being exacerbated as medical staff have even less time than before Covid-19 to recruit. “It is just not happening,” says Brook. “In up to 75% of cases, clinical trials for Phase II and Phase III run late. Such delays mean a trial rarely finishes on time, costing the pharmaceutical company not only more money than budgeted for but eating into the period of exclusivity and losing millions of dollars in lost sales. Poor patient recruitment and retention is to blame for 80% of all delays.”1
If this could be remedied, aside from enabling access to new and innovative medicines it would also make a dent in the patient backlog, Brook says. “Better treatments mean fewer people going into hospital and you relieve the burden of the hospital,” he adds.
Transforming the clinical trial model
Thankfully there are a number of solutions that could help to make this to happen, he says. “The first is clearly a higher investment to clear the backlog of those patients. The second is a greater reinventing of time to see research patients, and emphasising of the value of research patients to institutions.”
Thirdly, there’s the professional independent site management organisation – SMO – model, Brook says. These are sites which contract directly with pharma or CROs to find hundreds of patients who fit the protocol. These organisations proactively search for the patients with advertising as well as through networks of GP practices, patient groups, and their own databases.
Chris Dodd, Chief Commercial Officer at SMO Panthera Biopartners, explains that it intentionally partners with groups of amalgamated GP practices for access to larger patient databases. “We’ve tried to embed ourselves within these facilities – so physically place our buildings in these GP mega practices – and partner with them on a different scale,” he says, adding that this method leads to greater reach and quicker recruitment times.
“When we’re asking [doctors] to write to their patients with cardiovascular disease that are over the age of 55, instead of returning 200 patients, it returns 3,000 patients,” he says.
“Instead of this being a nurse and a doctor in a hospital, doing perhaps six hours on Friday afternoon and a little bit on Thursday evening, this is 15 to 20 people dedicated to one study, spending 40 hours a week to try and find that 3,000 start base and turn them into tens of randomised patients,” he explains. “It’s just a totally different scale of operation compared to the independent and public sector clinics and practices. Our overstretched healthcare workers just do not have the resources or the time to get similar results.”
Creating a good industrial model for conducting clinical studies can’t be a part-time practice, says Dr Simon Sinclair previously VP, Medical Affairs Lead, Medical devices, EMEA – J&J and Senior Director, Global Trial Optimization – Merck Research Laboratories. “You can’t dabble in this game.”
This proactive recruitment methodology shortens the timeline dramatically. Dodd explains: “All SMOs can speed up the process. Our model shows that we can be seven months in advance of a non-dedicated research site, representing millions of dollars in extra sales. While SMOs charge fees for the recruitment activities these are dwarfed by the savings for the sponsor.”
Not only do SMOs have access to huge patient populations, they also understand the behaviour of patients. This means that their feasibility models are not only much more accurate in guiding the sponsor in the planning of number of sites required, but also in the recruitment pattern.
“If an SMO has been doing clinical research in a given area, then they will have the longitudinal data set that can really inform how that patient population behaves,” says Sinclair. This is valuable to smaller and newer companies who lack access to that operational history but want to accelerate engagement with the right patient populations, he explained.
The SMO model does vary and can be comprised of standalone sites, sites in large GP practices, embedded in hospitals or a combination of these.
“The ideal world is where you have an SMO within a hospital or large practice,” Brook says. “You’ve got better access to patients, better access to specialist consultants, access to pathology and other screening technologies, but it’s run in a dedicated fashion and doesn’t detract from the daily activity of the hospital. In fact, it complements the facility by taking patients out of their system.”
The other great benefit of the SMO model is that staff work very hard to keep patients on the trial. They ensure that patients don’t wait to be seen, phone to remind patients of appointments, provide transport, and perhaps most importantly provide time for the patient to chat to the doctor, not only about the trial but also their general health. If any matters of concern are raised, they can be immediately referred to their own doctor.
Dodd explains that SMOs cuddle their patients in a way that public sites just don’t and most of their patients really enjoy the interaction. It is estimated that more than 18%2 of patients drop out of every clinical trial.
To further ensure compliance, SMOs only select easily accessible sites. This includes good public transport links and on-site parking, comfortable waiting areas with refreshments, as well as facilities for trial monitors and space for dedicated investigator rooms.
Supplementing this, Panthera has developed IT systems that support patients throughout the trial to ensure constant communication.
Sinclair comments: “While the independent SMO model is gaining traction in the UK, in the United States it is prevalent and there are a lot of healthcare institutions that are keen to be attached to an SMO. In other parts of the world, it’s still seen as something of an alien concept.”
The barriers to adopting new solutions
Although there are advantages to the emerging SMO model, there are barriers to its uptake. “There’s a challenge on the perception, particularly on price, because the upfront cost is greater even though it saves money in the longer term,” Brook says.
While SMOs charge for their services in candidate sourcing according to Dodd, Panthera is quite content to get paid on results. “We don’t get the majority of these payments unless we find the number of patients agreed upon.”
“If you put the numbers together, actually having the guaranteed recruitment within a guaranteed timeframe that an SMO gives you is more cost-effective, but our clients tend to look at the total cost rather than the cost of the delay,” Brook says. Daily delays, according to Pharmafile, can equate to between $600,000 and $8 million. That is without loss of sales due to generic competition”.
“Often those conversations are met with incredulity among sponsors,” says Sinclair. “’You must be kidding? If I spend half a million more on this, I’m going to get it in half the time?’ ‘Well, yes, actually. And we can show you why and how.’” It’s important, he explains, for an SMO to have an operational data track record in their back pocket to validate the numbers when talking to potential clients.
“If we could change the perception and present more realistic data on the overall delays and the cost of those delays, and how you could remove those delays by working with an SMO to guarantee delivery, then the cost-benefit becomes much more apparent,” Brook says, adding that academic research that conducts a cross-sectional analysis of multiple SMOs against the traditional model would be helpful.
In the UK Sinclair believes the relationship between SMOs and the healthcare system also needs to be improved upon, “so that the embedding of staff within the sophisticated healthcare organisation can become more commonplace.
“I think in countries like the UK, where you have a nationalised healthcare system, it can be quite difficult to embed that,” he says, “but if that can be remedied you’d have a really good model which would provide the professionalism of the SMO, access to patients and the screening, and other specialist services that the NHS could provide.”
Both Panthera and Synexus, another UK SMO, have achieved this at a few hospitals including Northumbria and Glasgow.
“If we could accelerate the evolution, then we are going to be able to do more research and prove or disprove the efficacy and safety of drugs, that will then ease the burden on the health systems that are currently at breaking point because we’ve got more effective treatments coming through,” Brook says.
DDW Volume 24 – Issue 1, Winter 2022/2023
About the author:
Leonie Onslow is an Independent Medical Writer based in West Sussex with over 35 years’ experience.