Is Clinical Supply Overage Always a Bad Thing?
Sponsors of clinical trials are often seen taking precautions to ensure patients never miss a dose.
This is done for three primary reasons:
To maintain patient safety and integrity.
Missed dosing can add up to cause significant delays in trials. These delays can ultimately cost sponsors $500,000 for lost sales and $40,000 in trial costs for every day that their medicine does not go to market.
As a sponsor, failing to support their patients can be a source of bad press, possibly impacting jobs, future business or even company valuation.
It is important to avoid losing patients from dropouts, as well as in mitigating risk to patient safety and efficacy due to missed doses. Any delays to enrollment due to stockouts can cause significant economic stress on a trial, potentially leading to profit loss. And from a statistical perspective, failing meet the protocol targets weakens any analysis.
The tried-and-true strategy in avoiding these risks is to overproduce the experimental drug, purchase a surplus of comparators and other supplies, and generally supply the trial greater than projected materials to reduce stock outages. But this of course leads to overage, a.k.a. waste, scraps. And that overage often fails to take into account complexity of different factors that should inform one’s supply strategies throughout a trial.
In this blog, we will explain what are some of the benefits and downsides to overage in trials, factors that affect supply overage, when overage may be a good thing, and some ways to find balance in your clinical trial supply chain.
What are the downsides of supply overage in clinical trials?
The downside of overage in clinical trial supply can be significant increases in costs due to production of unneeded batches, and unnecessary shipments. There is also the unnecessary generation of CO₂ emissions due to extra shipments.
What are the positive aspects of oversupply in trials?
By producing an abundance of supply stored at sites and depots, sponsors can avoid disruption and ensure continuity to their trials. They produce buffer quantities to account for deviations from expected enrollment across sites. And they can be prepared to replace lost, damaged or expired supplies.
What are some factors that create clinical supply overage?
There are several factors that create clinical supply overage. The most important contributors as it relates to clinical supply managers are:
Demand uncertainty
Clinical supply managers can estimate demand over time in a trial. But demand levels at different points of a trial are still largely unknown. The more sites you have, the more countries, the longer the trial duration, and the greater level of uncertainty exists for demand.
Other factors that influence demand are randomization, dose changes, stratification, weight-based (or "factor-based" more generally) dispensing, dropouts, and more.
Protocol amendments can have a tremendous impact on supply chain requirements and constitute another source of overage in relation to demand.
Labeling of supplies
Configuring labeling for specific countries or regions based on language limits the re-routing of kits elsewhere. This leads to overage by contributing to the overall lack of supply chain flexibility to meet shortages in certain areas or countries should they arise.
Supply chain network structure
The strategies used to deliver clinical supplies from central depots to patients can lead to overage. Every node in a supply chain (depot, site, pharmacy, etc.) is another place where kits could be left unused. This is why configuring an RTSM/IRT system to automate depot-to-site shipments can be instrumental in keeping the supply flow under control and in reducing stockouts and overage.
Shelf life
Sponsors often need to build in overage to account for the expiration of their experimental medicines. Inventory must be quickly replaced since expiries tend to be short, especially in earlier phases or early in a trial.
Various other factors
Things like temperature excursions, late approvals, political decisions, and acts of nature can impact the clinical supply chain and necessitate overage. Many of these factors lack predictability, but nevertheless can be dealt with quickly with the right monitoring technology and procedure in place.
When is overage of supply in clinical trials a good thing?
It can be advantageous for companies to produce overage strategically. Advanced forecasting systems like Trialzen can help sponsors recognize the value of oversupply for their trials.
Strategic overage can be allocated at certain sites or depots, for certain dispensing units and certain lots, depending on how a sophisticated forecasting and optimization tool recommends tweaks to a sponsor’s supply strategy. Since overage may already be a sunk cost, choosing where to allocate the overage for deployment is important to optimize their use. Cheaper production costs for drugs can also make overage less impactful, especially when shipment costs are comparatively more important, like in cold-chain trials.
Accounting for overage strategically may allow drug companies to consolidate their shipments to sites to minimize their shipment costs. It is ultimately a balance between what level of risk sponsors are ready to assume and the costs of shipments and materials. By electing to generate overage strategically, clinical supply managers can weigh a more comprehensive set of factors beyond projected demand to optimize their trial supply economics.
Overall, evaluating the risks and benefits of overage is important to understanding when it’s necessary to a trial and to what level.
How do you balance the need for adequate supply with the risks and costs of overage?
First of all, the need to plan is paramount. Utilizing best-of-breed forecasting solutions can ensure that you can plan with different scenarios in mind and optimize as actuals deviate from initial projections.
Secondly, a flexible, resilient supply chain means not only selecting the right depots and sites for your study, but in setting up RTSM/IRT parameters to ensure adequate supply and resupply for sites in line with demand needs.
Just-in-time manufacturing, packaging, and labeling can be especially useful for medicines that are more expensive to produce but require shorter production lead times.
Taking the time to regularly monitor and optimize your trial supply chain goes hand-in-hand with a good forecasting tool to ensure necessary adjustments as your trial moves along. This monitoring is also integral to assessing and mitigating specific potential risks that can befall your trial’s supply chain like a looming strike of medical workers in one of your trial’s participating countries.
Oversupply in clinical trials must be strategic
So, is oversupply in clinical trials always a bad thing? In short, no, it’s not always bad. For one, producing overage is a way to anticipate possible fluctuations in demand within a certain degree of predictability. They are necessary often for creating safety and continuity in trials, to make sure patients never miss a dose, which also ensures safety and reduces likelihood of dropouts. But oversupply increases cost of drug production, packaging, labeling, storage, shipping, and in taxing our environment with unnecessary CO₂ emissions.
Many things can influence clinical trial supply overage:
Enrollment at sites and other factors influencing demand
The way a trial’s supply network is structured and configured for regular and triggered shipments
Kit design, packaging and labeling of supplies
Shelf-life and expiration of lots
Various other factors influence to what degree oversupply affects a trial’s bottom line and its carbon footprint
Understanding the unique needs of your trial as it relates to countries, production, logistics, projected demand over time, and many other factors informs how much oversupply is necessary for your trials to run smoothly. Taking these and other variables into account as they fluctuate over time calls for robust forecasting and optimization processes. After all, it’s a fine line between good overage and bad overage, and finding that balance is critical to efficiency.
