Clinical trials were once easier to organize around broad categories. A patient had a disease, the study tested a treatment for that disease, and the trial design followed that structure.

That model still exists, but modern drug development has changed the question. In many areas, especially oncology, the question is no longer only whether a treatment works in a disease category. It is which patients are most likely to benefit, whose biology matters, and how treatment assignment should reflect what is known about the tumor, marker, pathway, or molecular profile.

That shift changed trial design. Biology was no longer only part of the scientific rationale. It began to influence how patients entered studies, how they were grouped, and what treatment they could receive.

The BATTLE-1 trial

A useful historical marker is BATTLE-1, the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination trial.

BATTLE-1 was a prospective, biopsy-mandated, biomarker-based, adaptively randomized Phase II trial in previously treated non-small cell lung cancer. The study required fresh tumor biopsies and used real-time molecular findings to help guide treatment assignment across targeted therapy options. It is often described as one of the first completed prospective studies in advanced lung cancer to integrate tumor profiling and adaptive randomization in this way (Kim et al., 2011; Liu et al., 2015).

That is the important shift for this series. The study was not only asking whether a treatment worked in lung cancer. It was asking whether treatment could be better matched to the biology of the patient’s disease.

In practical terms, that meant the trial design had to do more than enroll patients into standard arms. It had to account for tissue collection, biomarker analysis, marker-defined groups, treatment options, and assignment logic shaped by emerging information.

What the design changed

BATTLE-1 matters because it made biology operational.

A biomarker result is not just a data point. In this kind of study, it can affect what happens next. It can influence whether a patient qualifies, which group they belong to, which treatment they may receive, and how the study learns from prior patients.

That creates a different design challenge. The trial has to connect scientific information to patient movement. It has to ensure that the right data are available before assignment. It has to define what happens when a marker is positive, negative, unknown, insufficient, or delayed. It has to decide whether assignment is equal, adaptive, or linked to accumulating response data.

These are not abstract scientific details. They shape the conduct of the study.

The operational question becomes: how does the trial make sure that the biology used to guide the design is reflected correctly at the point where patients are screened, assigned, treated, and followed?

What biology changes operationally

BATTLE-1 sits at an important point in the broader move toward precision medicine. Since then, biomarker-led and targeted studies have become far more common and far more varied.

Modern studies may use central lab results, local testing, companion diagnostic requirements, genomic profiles, tumor mutations, expression levels, prior treatment history, or disease subtypes to determine where a patient belongs. Some studies may include multiple cohorts defined by biology. Others may use biomarker results to assign treatment, open expansion groups, stratify randomization, or determine whether a patient can continue into a specific pathway.

That means the trial no longer has one simple patient route.

A patient’s path may depend on test availability, result timing, marker status, cohort capacity, treatment availability, country participation, or protocol-specific rules. A site may not be able to move the patient forward until a required result is available. A cohort may be open for one marker group but closed for another. A treatment may be appropriate scientifically but unavailable operationally if supply, region, or study status does not align.

This is where biology-led design becomes an execution challenge. The science may define the pathway, but the study still needs a controlled way to operate it.

RTSM impact

In a biomarker-led study, assignment logic and supply planning have to stay connected.

Biomarker-defined groups may not enroll evenly across sites, countries, depots, or treatment arms. One subgroup may appear slowly across many sites. Another may enroll quickly in a small number of regions. Treatment demand can shift based on which patients qualify, which cohorts are open, and how assignment rules apply over time.

RTSM needs to reflect the approved assignment logic, but it also needs to support the supply reality created by that logic. If cohort status, treatment assignment, and supply assumptions are not aligned, the study may identify the right patient but still struggle to make the right treatment available at the right place and time.

When biology drives execution

BATTLE-1 matters because biomarker information helped determine treatment assignment. The biology did not sit outside the study. It shaped how patients moved through it (Kim et al., 2011; Liu et al., 2015).

For modern trials, that creates a practical execution challenge. Biology-led design can narrow populations, shift demand, and make supply needs less predictable. RTSM has to support the assignment rules while keeping supply planning close to what is actually happening in the study.

That is the operational translation required when science leads the design.

References

Kim, E. S., Herbst, R. S., Wistuba, I. I., Lee, J. J., Blumenschein, G. R., Jr., Tsao, A., Stewart, D. J., Hicks, M. E., Erasmus, J., Gupta, S., Alden, C. M., Liu, S., Tang, X., Khuri, F. R., Tran, H. T., Johnson, B. E., Heymach, J. V., Mao, L., Fossella, F., Kies, M. S., ... Hong, W. K. (2011). The BATTLE trial: Personalizing therapy for lung cancer. Cancer Discovery, 1(1), 44-53. https://doi.org/10.1158/2159-8274.CD-10-0010

Liu, S., Lee, J. J., Wistuba, I. I., Tannir, N. M., Kantarjian, H. M., & Kurzrock, R. (2015). An overview of the design and conduct of the BATTLE trials. Chinese Clinical Oncology, 4(3), 33. https://doi.org/10.3978/j.issn.2304-3865.2015.05.04