How can study teams deal with increasing trial complexity?
Last year, a Tufts analysis of 9,737 clinical trial protocols from 178 pharma and biotech firms found that companies are collecting data on 86% more endpoints than they did in the last decade. Companies are aiming for global approvals, requiring trials to run simultaneously in multiple countries, which each have their own regulatory and ethical procedures. According to Tufts, Phase III trials have seen the biggest increase in complexity, with the number of support sites increasing by 63%.
More complex trials mean more complex protocols, and one of the key impacts of this is the likelihood of numerous protocol amendments. According to Ken Getz, a single typical protocol amendment can take three months and result in half a million dollars in direct costs. Since about 40% of all amendments occur before the first patient has received their first dose, it’s easy to see how complex trials present unprecedented executional challenges for sites and study managers alike.
Why are modern trial designs more complex?
Many of today’s trials are developing drugs for patients with specific mutations or rare diseases, resulting in an entirely new lexicon:
- Adaptive trials – defined by the FDA as “a clinical trial design that allows for prospectively planned modifications to one or more aspects of the design based on accumulating data from subjects in the trial.”.
- Basket trials – established in oncology studies, to test the effect of one drug on a single mutation in a variety of different tumor types, at the same time.
- Umbrella trials – these include many different treatment arms within one trial. People are assigned to a treatment arm based on the type and specific molecular makeup of their cancer.
These different types of trial design require markedly different workflows in comparison to traditional randomized controlled trials. This is especially true in the case of adaptive trial designs, where decisions are based on any number of different scenarios that play out as more patient data is collected.
A further challenge is posed by the increasing number of endpoints. In addition to the data being collected for primary endpoints, sponsors are now gathering data on an increasing number of secondary and tertiary endpoints. And the sources of these data are ever-expanding: from blood tests and imaging collected during site visits, to patient-reported outcome data collected via mobile technology and wearables. The volume and variety of data that needs to be managed is unprecedented.
What does the trial complexity mean for the site?
Increasing trial complexity presents a new range of challenges for site teams and study managers. The most obvious one is protocol complexity. Having a protocol that is overly burdensome for patients and site staff alike will only perpetuate the ‘one and done’ syndrome, where investigators and trial participants who have had a bad trial experience and never take part in another..
Right now, industry is taking something of a ‘sticking plaster’ approach to dealing with the complexity of trials, by finding solutions to individual operational challenges, when what’s needed is a holistic, transformational approach that strikes a balance between the scientific trial objectives and feasible operational execution.
What can be done to overcome today’s challenges?
The good news is that embracing new trial designs will, by necessity, require substantial upfront planning that could improve operational execution. Key to this is embracing new technologies that make life simpler for site teams and patients. This includes making it easy for site teams and patients to understand and comply with the protocol. It means implementing technology that allows you to communicate protocol amendments or other essential information to everyone concerned, quickly and with a clear audit trail. And it means having access to the data you need, when you need it, to enable agile data-driven decisions. Spending more time upfront on considering how best to set up your trial processes and platforms to support sites, study teams, and patients will be key to navigating the innovative new trials designs of tomorrow.