It's getting harder for sites. It's getting harder for patients. And that's not the only problem.
If you look at the data trends over the last decade, there's no avoiding the truth: clinical trials are getting more complex, and every year. According to Tufts's Ken Getz, "protocol design elements associated with protocol execution have grown rapidly" as demonstrated in a comprehensive study comparing 2010-2005 and 2011-2015. Getz and his team's research indicated that even with the decline of some routine procedures – like blood tests – overall the cost per volunteer has grown due to a hefty increase in the total number of procedures: a 69% growth in Phase II and a 49% growth in Phase III.
Outside of Tufts, there is little discussion as to what this means for sponsors and, most importantly, for patients. It's an ugly truth buried in proposals and budgets that many CROs are just willing to gloss over and avoid. We are asking more of patients, more of sites, and as medicine becomes more personalized and integrates more technology, the budgetary bloat easily gets out of hand.
But what does that mean for patient enrollment? Are more complex trials positively impacting patient recruitment? With no end in sight to the constant technological and data-centric "solutions" in the industry, the outcomes should be the best indication.
Getz says that's not the case at all: "These study findings are striking given research linking protocol complexity to longer cycle times, higher numbers of protocol amendments and lower patient recruitment and retention rates. The collection of excessive and unnecessary clinical data may also compromise data integrity and analysis, lead to higher error rates, drive longer study durations, and delay submissions to regulatory agencies."
So this steep increase in complexities isn't actually moving the dial.
The cost of big promises in the face of over-complicated clinical trials
From the start, CROs need to be candid with sponsors about trial complexities and their ramifications in the process. It's easy to fall into a mode of wanting to please everyone. A trial in a promising therapeutic area or with an exciting new molecule might get teams ready to bend over backward to make an appealing proposal and win business. But half-empty promises don't lead to good relationships, repeat business, or trust. The biggest issue with over-promising and under-delivering is the impact on budgets and, ultimately, lackluster patient enrollment.
Sponsors end up burned when CROs are falling short of tackling challenging protocols, but they're not the only ones. Patients suffer, too. Due to the collaborative nature of protocol development, it's easy for each "piece" to fall into place but not work harmoniously as a whole. CROs should be part of the conversation, helping to advocate for protocol clarity aimed at making the enrollment process easier on the patient. Often, overlooked components of a protocol – like considering the burden on the patients from multiple angles – fall by the wayside.
Rhonda Critchlow, PSI's Senior Director, Operations Oncology at PSI, explains: "We really should be tapping into patient advocacy groups, listening to the key opinion leaders at sites and asking: is this protocol going to be burdensome on the patient? Do we really need to do an 8 hour PK and a 12 hour PK, for example." This means considering operational, real-world applications. Additional PK infusions mean more staff needed, more attention given to patients who will need more accommodations and a likelihood that many patients will simply feel that the ask is too high. These kinds of ramifications must be addressed early on in protocol discussions, and the right CRO will spot possible pain points.
Too many interventions may make the clinical trial unappealing to the patient who is often already under a lot of medical treatment. Unless the science is truly groundbreaking, it's a difficult sell to patients and their families who may be on limited time as it is. And although patients receive informed consent documents, they're often not provided enough information written in lay person's perspective, presented in a way that clearly outlines the risks and the benefits of the trial. It puts a bit too much of the responsibility to put that information solely in the hands of investigators and site coordinators when CROs can partner with sponsors to provide that level of detail earlier on in the process.
When technology becomes just another complication
New technologies crop up in clinical trials every few seconds, it seems, and while innovation is tantalizing – and can help smooth over difficult aspects of running clinical trials – they can also add undue complications. The trouble is that technologies aren't one size fits all: not for every sponsor, not for every indication, not for every site, and especially not for every patient.
Working in an elderly population, for example, may end up benefiting a vendor but not actually impacting enrollment at all. eDiaries, for example, may be a roadblock for elderly patients with visual or hearing impairment or without access to the internet. Software designed to monitor taking medicine might glitch out and give false positives or negatives, putting the study at risk, when an office visit would have sufficed. The focus should never be on the technology: it should start with the patient.
The same can be said for a wide array of technological add-ons. If they're not benefitting the patient, if they're not going to help move the dial toward faster, more efficient enrollment, it's important to take a very good look at the whys and hows. It's easy to be distracted by the new and now, but just because the technology is state-of-the-art, it doesn't mean the impact is measurable or beneficial to the study on the whole.
But sponsors need to be willing to listen, too
Spilling hard truths that sponsors don't want to hear can be a precarious situation. But with the right relationships, sponsors will collaborate with the CRO, especially when it comes to patient enrollment issues. "PSI never shows them the problem without giving them an alternative solution," says Critchlow. "Sometimes the enrollment rate might be lower than what the sponsor is seeing, and not every client will not want to hear the reality. Ultimately it comes down to patient lives and costs along the journey, and that's always our focus."