In the simplest terms, clinical endpoints refer to the objectively measurable parameters that indicate whether the drug candidate under consideration is beneficial. Clinical endpoints are measures that show the extent of patient comfort, functionality, and survival.
A biomarker is a molecule, a gene, or a characteristic occurring naturally, which acts as a signal for biological processes. It also points to the presence of pathological conditions, if any.
In the context of drug development, biomarkers are measurable indicators of normal biological functions, pathogenic conditions, and the response to pharmacological intervention.
This is why biomarker testing and biomarker validation can provide clinically validated surrogate endpoints. These surrogate endpoints are necessary before direct validation of clinically meaningful parameters in phase 3 of clinical trials.
The Link of Clinically Meaningful Endpoints With Patient-Centric Healthcare
The patient-centric care perspective makes meaningful clinical endpoints particularly crucial. Patient-centric care emphasizes that a one-size-fits-all approach may not work with therapeutics. This is why the stress on how a patient “feels, functions, and survives” as meaningful clinical endpoints.
This is also where effective biomarker assays play an essential role in generating clinically validated surrogate endpoints. Cancer therapy has demonstrated this most effectively. The “right drug in the right dose for the right patient” approach has made biomarker assays especially critical.
Carefully designed biomarker testing has emerged as increasingly more relevant in the development and approval of anticancer drugs. Biomarker validation is a necessary means of ascertaining the efficacy of biomarker testing.
The Objective And Subjective Aspects Of Clinically Meaningful Endpoints
No drug is entirely free from safety risks. A patient can benefit from a drug only if it improves their survival chances. We can measure it directly by the extent to which symptoms reduce, and functionality improves because of therapeutic intervention.
A new drug achieves such clinically significant endpoints if it does not increase the chances of a negative impact. An increase in the chances of a stroke, for example. Together, these directly verifiable clinical endpoints constitute the basis of new drug approval.
It is possible to objectively measure the reduction in symptoms, improvement in functionality, and no harmful side effects.
However, patients must be able to detect such changes as well. That generates the subjective element of a patient’s feelings of improved quality of life because of the new therapeutic intervention.
From the patient-centric care perspective, this subjective element receives equal weight in the sphere of FDA approval for a new therapeutic.
Why Biomarker Assays Are Relevant
Efficient and effective biomarker assays are critical in generating clinically validated surrogate endpoints. These are indicators of the likely effects of a new drug on the intended patient population.
Surrogate endpoints get generated in laboratory settings to reflect the benefit-to-risk profile of a new drug. We call them surrogate as we use a substitute for the targeted patient population in lab experiments.
The actual experiment involves biomarker testing, though just generating data about surrogate endpoints is not enough. It is necessary to have reliable data to demonstrate that the surrogate endpoints resemble clinically meaningful parameters. This is the process of biomarker validation.
A Word Of Caution
Incidents of surrogate endpoints failing to produce clinically meaningful parameters have resulted in considerable scepticism around their efficacy. It is critical to have well-controlled trials in adequate numbers for surrogate endpoints to match with clinically significant endpoints in the targeted patient population.