In the ever-shifting landscape of drug development and approval and pricing portfolios, decision-makers require robust tools to help them make solid decisions about a drug candidate’s likely success in clinical trials, the probability that it will obtain regulatory approval, and its likely success in a competitive market.
Objective and data-driven methods are needed to reliably assess an asset’s likelihood of success, inform decision-making and provide a documented, well-vetted strategic and holistic analysis of the risks.
Various metrics and combinations are used to assess the risk of individual steps in drug development or to refer to the overall risk of successfully getting a drug approved, priced and sold.
This list summarizes the terms that are commonly used:
- Probability of success (POS)
- Likelihood of approval (LOA)
- Probability of phase transition (POPT)
- Probability of launch (POL)
- Probability of technical success (PTS)
- Probability of regulatory success (PTRS)
- Probability of technical and regulatory success (PTRS)
- Probability of pricing and access success (PPAS)
While these terms sound similar, are closely related, and are often used somewhat interchangeably, they (mostly) have distinct differences. Adding inconsistency to the complexity is the fact that these terms are not used consistently across the industry and that one author’s or company’s POS might be another’s LOA or PTRS.
For this blog, we worked through several papers and publications to sort the definitions and clarify the nomenclature of drug development success.
A Confusing Array of Probabilities and Likelihoods
We’ll start by defining these terms and highlighting the (sometimes subtle) differences.
- Probability of success (POS) refers to the probability that a drug candidate will successfully navigate the entire development process and eventually be approved and marketed. It includes all stages from discovery through preclinical and clinical trials to regulatory approval and measures the cumulative risks at each stage, including scientific, clinical, regulatory and commercial factors.
- Likelihood of approval (LOA) is closely related to POS and often used interchangeably. However, the focus is specifically on the final stages of development, i.e. Phase 3 trials and especially regulatory review. Some researchers use LOA for the overall probability of success, i.e. moving a drug from Phase 1 to approval, and therefore to express the same concept as POS.
- Probability of phase transition (POPT) refers to the likelihood that a drug candidate will successfully move from one specific phase of development to the next (e.g., from Phase 2 to Phase 3). The POPT for each phase is influenced by the criteria important for the specific phase, e.g. safety in phase 1, efficacy in phase 2. Overall the focus is narrower and on the individual steps in the development process rather than the overall journey.
- Probability of launch (POL) this is similar to POS but somewhat more comprehensive. It expresses the likelihood that a drug completes all clinical trial phases successfully, navigates regulatory approval and is launched. This metric can incorporate both the POS as well as additional factors influencing the final market entry, e.g., manufacturing capabilities, market conditions and commercial strategy. However, some authors define POL as the probability of the project being successful through all phases of development, which is very similar to POS.
- Probability of technical success (PTS) refers to the probability that a drug successfully completes the clinical trials. The focus is specifically on the technical challenges a drug candidate faces during clinical trials.
- Probability of regulatory success (PRS) refers to the probability that a drug successfully makes it through the regulatory review process and achieves market approval.
- Probability of technical and regulatory success (PTRS) is a broad term that encompasses not only the likelihood of a drug successfully navigating clinical trials (the technical aspect) but also the probability of receiving regulatory approval from agencies like the FDA (the regulatory aspect). PTRS can be calculated for each phase of development.
PTRS can also be calculated as the product of PTS and PRS. By breaking down the technical (PRS) and regulatory aspects (PRS), PTRS offers additional granularity compared to POS and LOA.
- Probability of pricing and access success (PPAS) is a relatively new concept that measures an asset’s pricing and market access risk, considering the therapeutic area, region and expected launch timing.
Similarities and Differences
These definitions related to assessing the risk of various stages or the entire drug development all broadly refer to estimating the chances of a drug candidate successfully progressing through clinical development, receiving regulatory approval and reaching the market and, in some cases, successfully competing in the market.
They are all used to understand and manage risks associated with drug development and each plays an important role in informing strategic decisions, resource allocation, and investment in drug development programs.
The terms differ in whether they focus on specific aspects of the entire process or try to assess the overall probability that a drug will be successful in clinical trials, achieve regulatory approval and/or be successful in the market.
Here’s Our Conclusion Around Drug Development Success Terms
The nomenclature around risk and likelihood of success in drug development is not standardized. While there seems to be fairly broad consensus around some terms, e.g. PTRS, other terms, e.g. LOA and POL are not used consistently in the literature.
These metrics play an important role in decision-making, guide strategic planning and investment decisions, help companies allocate resources more efficiently, better manage risk, and make informed decisions about continuing, modifying, or halting development programs.
It would be ideal to have standardized definitions for all these terms to simplify communication and minimize misunderstandings. Without that consensus, it’s best never to assume everyone is on the same page regarding terminology. Take the time to align on the terms and their definitions upfront.
At Intelligencia AI, we understand how important it is to speak the same language and use the vernacular that resonates with our pharmaceutical customers. We take the time to align on expectations, and within our patented-PTRS solution, we define and provide more context on the terminology in our solution. It’s one of many ways to ensure success for all parties.
If you want to read about some other industry terminology, check out our growing drug development, risk assessment and AI glossary of terms and FAQ here.