When it comes to oncology clinical trials, it’s never too early to start thinking about comparators. Almost all late-stage cancer clinical trials pit experimental treatments against active, standard-of-care comparators, which, increasingly, are running into widespread shortages.
According to the FDA, 12 approved oncology drugs are currently in shortages, including common drugs like Bristol Myers Squibb’s Onureg (azacitidine) and Pfizer’s Fludara (fludarabine). With ballooning demand for new cancer treatments and increasingly strained global supply chains, experts predict oncology drug shortages are unlikely to diminish anytime soon.
Currently, there are over 4,000 ongoing oncology drug trials that involve a drug the FDA lists as under shortage, according to GlobalData’s Clinical Trials Database. This amounts to 28% of ongoing Phase III oncology drug trials and 19% of such Phase II trials. GlobalData is the parent company of Clinical Trials Arena.
To plan ahead for possible shortages, experts say sponsors should think hard about sourcing strategies, weighing the advantages of localized and centralized sourcing based on their particular trial needs. In addition, improved drug waste management and back-up comparator options can all go a long way towards keeping clinical trials on track.
Challenges of oncology trials
Drug supply is particularly difficult to manage in oncology trials due to higher uncertainties in dose-limiting toxicities and patient dropouts and deaths, explains N-Side’s Amaury Jeandrain. Sourcing oncology comparators only adds to the challenge, as many comparators are more expensive and involve more regulatory hurdles than drugs in other indications, adds Sylvain Berthelot, senior voice of customer & strategy director at Calyx.
To efficiently source oncology comparators and minimize potential drug waste, sponsors should deliberately choose between centralized and localized sourcing options based on the needs of any given trial, Berthelot says.
Under a centralized sourcing strategy, a sponsor orders and stockpiles drug supply in a limited set of centers, distributing drug supply according to each trial site’s needs. This allows sponsors to better manage drug supply needs with interactive response technology (IRT), granting the flexibility to respond to unexpected recruitment challenges in specific sites, Berthelot explains.
Meanwhile, localized sourcing leaves the responsibility of procuring comparators to individual sites and investigators. This strategy is useful for navigating a country’s individual regulatory and import requirements, especially when there is wide variability among trial locations, Berthelot notes.
Overall, the large majority of oncology drug trials using at least one drug in shortage are based in only one country, where the aforementioned advantages of centralized sourcing could be more pronounced. The most multinational trials occur at the Phase III stage, accounting for roughly a third of such trials, according to GlobalData’s database.
New strategies for waste reduction
Given the high cost of oncology comparators—and especially comparators in shortage—predicting supply chain needs to minimize waste should be top of mind for sponsors, Berthelot and Jeandrain say. New technologies, such as artificial intelligence (AI) that predicts drug needs on a per-patient and per-site basis, can help sponsors rein in excessive drug waste, Berthelot notes. Eventually, closed-loop systems, where an IRT engine feeds a forecasting engine with real-time metrics on recruitment, could automate the drug waste management process, he says.
Most companies go into trials with a goal of limiting drug waste at a certain level, such as no more than 20%, but fail to actively collect data on drug waste, he adds. Though data makes it difficult to estimate the full extent of drug waste, some estimates indicate up to 50% of drug supply in oncology clinical trials ultimately goes to waste, Jeandrain says.
Meanwhile, US Medicare data on drug waste among approved drugs in oncology suggests the total monetary cost of drug waste can be exorbitantly high. According to a 2020 Medicare report, seven of the 10 drugs with the highest waste were in oncology, amounting to losses of over $300 million in these drugs alone.
Back-up oncology comparators
Given the unpredictability of drug shortages, it is important for sponsors using oncology comparators to have back-up options in mind. One executive of a publicly traded biotech in the oncology space tells Clinical Trials Arena that his company previously ran into significant delays when an ongoing trial faced a shortage of Celgene’s Abraxane (nab-paclitaxel). As a result, the executive explains, many sites began substituting Bristol Myers Squibb’sTaxol (paclitaxel) for the chemotherapy.
Meanwhile, the executive adds that many sponsors in the cell therapy space are facing significant shortages of fludarabine, a chemotherapy that Pfizer discontinued in 2020. In the journal Transplant Cell Therapy, one paper cited the need to prioritize building institutional algorithms for maintaining ongoing clinical trials using fludarabine and other drugs in shortage.
Meanwhile, although industry sponsors a considerable number of oncology trials, most studies involving oncology drugs in shortages are sponsored by academic research institutions. Around 81% of Phase II and 69% of Phase III oncology trials using drugs in shortage are institution-sponsored, according to GlobalData’s database.
Oncology drug development continues strong
Overall, oncology clinical trials are notoriously difficult to run, with constantly evolving standards of care, complicated regulatory barriers, and now, growing supply chain shortages. But with high investment and continued regulatory support, drug development in oncology is unlikely to slow down.
While unmet need remains high and patients continue to demand new cancer treatments, sponsors must select comparators and prepare for all contingencies early to keep their trials running according to plan.
- Nearly 1-in-5 Phase II trials and over 1-in-4 Phase III trials in oncology use drugs that the FDA lists as “currently in shortage,” heightening the risk of higher costs and study delays and terminations.
- When sourcing comparators, sponsors should use centralized options to streamline IRT systems or localized options to accommodate diverse trial locations and regulations, depending on the specific study design.
- New strategies for waste reduction, including IRT and predictive AI, can help sponsors get more out of limited drug supply.
- Sponsors should have a Plan B ready for any oncology comparator they intend to use in clinical trials, and drug shortages can prove highly unpredictable.
Methodology: Charts in this article use a dataset of all ongoing oncology trials in GlobalData’s database that include at least one drug listed as “currently in shortage” from the FDA’s Drug Shortages Database as of November 14, 2022.