Biomarker Assay-Driven Clinical Trials

Biomarker assay-driven clinical trials offer researchers a way to gather information on the effects of a drug within an organism that is being studied. 

With their ability to help identify study populations, discover side effects, and track therapeutic response, biomarkers can be very useful in clinical trials and drug development. While biomarker development is a long process with several stages, in many trials, using biomarkers can be the key to unlocking disease characteristics. 

Compared to non-biomarker-driven studies, a clinical trial that involves biomarker assays may be enriched by an ability to evaluate therapeutic intervention more effectively, increasing the success of drug development and helping to cut costs.

This article looks at biomarker strategies and the way biomarker assays are integrated into clinical trials.

Biomarker Strategies

Trial investigators wishing to optimize their trials can utilize experienced laboratory service providers to advise and guide them on biomarker strategies. The involvement of a trusted laboratory partner to provide its input on biomarkers from the outset of preclinical stages allows trial protocols – and as a result, trial outcomes – to be optimized.

Biomarker-Driven Trial Design

Molecular profiling at the level of individual patients is becoming more affordable and accessible. For this reason, an increasing number of clinical trials are being driven by biomarkers. This allows disease management to be both optimized and personalized. 

Whereas conventional clinical trials focused on evaluating the effect of treatment in populations are defined by histology – that is, the microscopic study of organs and tissues – biomarker-driven trial designs demand additional considerations during planning. There are several factors that rely heavily on the nature of the biomarkers themselves, how they are used clinically, and their performance level. Biomarker-driven trials have also led to the requirement of multi-histology and multi-agent master protocols and platform trials, which present their own advantages, as well as operational challenges and limitations, which we will discuss in the following section.

Mitigating the Limitations of Biomarker Designs

While biomarkers can open the door to more personalized disease management, robust methodology is needed for biomarker assay-driven clinical trials, in order to identify participant and treatment groups correctly. 

The ‘enrichment design’ for biomarker-driven clinical trials randomly assigns biomarker-positive patients to the targeted arm. This design is the most popular, but it can only be recommended when the biomarker predicts the response perfectly. That’s to ensure that biomarker-negative patients aren’t denied a treatment that they would have benefited from otherwise.

Aside from the enrichment design, there is a substantial number of other designs used in biomarker-driven clinical trials. A review of study designs for clinical trials applied to personalised medicine identified 21 trial designs in total, along with 10 subtypes. 

When there is a challenge to answer several clinical research questions in one study, more complex trial designs have emerged, involving separate parts that may constitute individual clinical trials or are characterised by significant prospective adaptations. These complex trial designs include:

• Basket trial design – when patients with heterogeneous diagnoses and similar disease mechanisms are tested with the same targeted therapy.
• Platform trial design – allowing multiple targeted therapies to be continually tested in patients with the same disease
• Umbrella trial design – enabling the evaluation of multiple treatment options in patient groups that present the same disease with differing genetic mutations. 

Methodological challenges present themselves in various aspects of study design, including biomarker stratification and biomarker validation. Complex trial designs often demand an independent statistical analysis for every subprotocol.

Biomarker Assay Development

After biomarker candidates are discovered, there is an onus on biomarker validation to help clinical trials improve their chances of success. Research has shown that when biomarkers are used in clinical research, they can triple the success rate of drug development. This makes biomarker assay development crucial to many clinical trials.

Whether methods are provided by the research and development team of a laboratory partner, or by a trial investigator independently, biomarker assays allow researchers to gather valuable data, monitor treatment response, and tailor treatments based on individual patient characteristics via precise and personalized approaches.

What is a Biomarker Assay?

Biomarker assays are tests used to measure biomarkers in biological samples, such as blood or tissue. In clinical trials, biomarker assays are crucial for evaluating the safety and efficacy of investigational therapies, as well as for identifying patient subgroups that may benefit most from treatment.

By using biomarker assays, researchers can make more informed decisions about which drug candidates to advance to clinical trials, how to personalize treatment for individual patients, and how to measure the success of a drug in development.

H2: Opportunities and challenges of biomarker-driven precision drug development

Two main aims of drug development have been identified as being to 1) validate a clinically efficacious dose and 2) define a disease state. A study summarised this as “finding the dose that will be effective for a defined group of patients while causing the least side effects”.

Biomarker assay development is central to both these concepts, going hand-in-hand with precision drug development and providing different results that help build a more robust picture.

Conclusion

The importance of biomarker driven drug development and biomarker assay development shows no signs of diminishing in the future. 

With the opportunity to create more personalized and targeted treatments while increasing efficiency and cutting costs, harnessing advances in biomarker development is likely to remain key to the success of many trials in both pre-clinical and clinical stages. 

Why Cerba Research?

Cerba Research offers unmatched biomarker capacities, giving clinical trials the benefit of skilled scientists with experience of biomarker validation, biomarker testing, and working with biomarker-driven designs. With Cerba Research’s biomarker and companion diagnostic services operated continuously across a global network, R&D productivity can be fully optimised.