Budget Proposals For Industry-Sponsored Pediatric Trials Need Renegotiating
By Deborah Borfitz
June 28, 2023 | Many sites engaged in industry-sponsored pediatric clinical trials are struggling to make them monetarily feasible because sponsors often apply the same budget figures used for adult trials and sites may be unaccustomed to talking about line-item costs for different procedures. The risk of getting the numbers wrong is both more likely and more fiscally damaging for everyone involved, according to Jenny Kindblom, M.D., Ph.D., associate professor at the Institute of Medicine, Sahlgrenska Academy, University of Gothenburg (Sweden), and senior consultant clinical pharmacologist at Sahlgrenska University Hospital.
The situation can be even more challenging across much of Europe, where healthcare is publicly financed and may itself be underfinanced. Small, inexperienced sites may not recognize that the budget offered by a sponsor is low relative to the anticipated cost of research-related activities they’re expected to deliver—and they probably have no one on staff with the time or skillset to negotiate a more equitable deal.
But if they did, the position would easily pay for itself, says Stavros Koulizakos, the team expert in charge of budget and contractual matters for the pediatric clinical studies underway at Sahlgrenska University Hospital. He and Kindblom have been trying to educate current and future pediatric investigators about the cost realities of this line of work and the return on investment of having a dedicated team member for reviewing and renegotiating study budgets with sponsors.
As a study on the matter recently revealed (Acta Paediatrica, DOI: 10.1111/apa.16808), a substantial portion of trial-related costs go uncovered if the initial budget proposed by study sponsors is accepted. True costs were shown to be a whopping 59% higher, on average, than the original offer and the central problem is that the figures are based on adult trials with no adjustments made for the realities of the pediatric setting.
Time and Travel
The published study was based on 10 trials sponsored by the pharmaceutical industry at the Pediatric Clinical Research Center at Sahlgrenska University Hospital. Most of the kids were seriously ill with conditions such as rheumatic heart disease and cancer and already under stress before having to make what is sometimes a three- or four-hour drive to the hospital for study visits involving potentially unpleasant procedures, points out Koulizakos.
Fair compensation for the cost of travel expenses of patients and their family members—including gas as well as food and hotel bills—is particularly critical to ensuring their continued participation at least remains economically feasible, he continues. For studies that go on for three or four years, those costs can be “quite significant” for families. Experience has shown that study visits also tend to go smoother, and faster, if study participants get to see the same study nurse each time.
Surprise is the common response to the sums that can be lost by the failure to negotiate, Koulizakos says. Encouragingly, when real costs are properly analyzed and explained line by line a revised budget will often get approved “right away.”
Budgets need to account for not only fixed costs, such as the cost of performing a colonoscopy, but also the time it takes an investigator to perform a neurological exam or the study nurse to report adverse events in the electronic case report form portal. At Sahlgrenska University Hospital, cost calculations are made off a person’s salary and broken down to the five-minute level based on time estimates by study coordinators for the different required protocol activities.
Clinical trial budgets are difficult propositions under the best of circumstances, but pediatric studies are a new level of complicated for savvy negotiators because they must factor in the reality that kids will be kids and cannot be expected to act like adults, says Koulizakos. They more often need a break from the rigors of study participation and parents as well as extra staff usually need to get involved.
Younger children may need sedating before some procedures, including spinal biopsies and MRIs, which increase the cost due to the involvement of a pediatric anesthesiologist, the room for administering the pain-numbing medications, and perhaps an additional nurse who has anesthesiology experience. Determining these “hidden costs” isn’t an exact science, he says, as it is not always possible to know in advance if children will fear a study-related procedure and require calming before they feel safe enough to participate.
Even performing something as seemingly straightforward as venipuncture can take a lot more time, adds Kindblom. To keep children distracted long enough for blood draws at the hospital, it is sometimes helpful to bring in someone to blow soap bubbles. Study visits can unpredictably and unavoidably slow down whenever a young participant arrives in a foul mood.
In any given year, Koulizakos might review and renegotiate budgets for up to 60 industry-sponsored clinical trials. This is in addition to the many academic studies that come through his desk with limited available funding and “less room for detailed examination,” he says.
Study agreements with industry sponsors can always be amended later, but revisiting the budget eats up time and is thus better avoided, especially when costs can be anticipated in advance, continues Koulizakos. The entire budget review and negotiation process currently takes 8 to 12 weeks and shrinking that period is partially dependent on collaborators across multiple hospital departments as well as the response speed of contract research organizations working on the sponsor’s behalf.
The consequences of the current underfunding of pediatric studies are potentially dire, says Kindblom. “We need to have clinical trials going on at hospitals because there is so much that needs to be done for children to get good medicines that are documented scientifically in the same way as [they are in] adults.” The only sustainable way forward is for industry sponsors and trial sites to equitably share the cost of study activities, she adds. “It’s as simple as that.”