Clinical Research: Phase 1 - Phase 4

Operationalizing Biomarker-Guided Oncology Trials: Planning for Success

Advances in genomic and proteomic technologies have led to the identification of numerous biomarkers with potential clinical utility in oncology, including gene mutations, gene amplifications, gene expression signatures, and altered proteins. To date, more than 1,500 potential oncology biomarkers have been identified in the preclinical setting. Among these, approximately half are being studied in active or planned clinical trials, predominantly for immune-oncology drugs. As biomarker-guided oncology trials proliferate, an increasing number of sponsors are tasked with operationalizing these studies within a complex, competitive, and constantly evolving environment.

In this blog, we share how to plan for success in 3 key areas of study execution: selecting the right sites for patient recruitment, managing data, and coordinating global trials.

Site selection and patient recruitment

Recruitment can be resource-intensive, especially when the molecular aberration of interest is rare. Developing a deep understanding of the biomarker of interest and its prevalence—which may vary by location and among races and ethnicities—can help sponsors and CROs identify the most promising geographies, sites, and predicted enrollment rates.

As more sites begin performing next generation sequencing (NGS) as part of their standard of care, it may be possible to access blinded gene mutation or biomarker data to inform site selection. In some cases, that data may exist in the site medical records in formats such as PDFs that are not easy to interrogate. However, recent advances in technology have revolutionized access to biomarker information by enabling upload of these data into electronic medical records. If potential sites already perform biomarker screening as part of their standard of care, it may be possible to pre-screen patients for eligibility, speeding up enrollment.

Qualified sites must have access to the target population, as well as experience in biomarker-guided studies. The site qualification process should also include confirmation that each site has access to any specialized equipment or data management software necessary to fulfill protocol requirements.

With the rise in consumer-targeted DNA testing, informed patients may be empowered to use their own mutation data to identify clinical trials for which they might be eligible. In the years to come, enhanced data sharing may help to further accelerate patient recruitment. This open science approach is still emerging, and large, readily available, commonly structured datasets are still limited, but some national and global cohorts are allowing researchers from around the world to access their data. For example, the International Hundred Thousand Plus Cohort Consortium has brought together over 100 cohorts in 43 countries comprising more than 50 million participants.1 In addition, the Global Alliance for Genomics and Health is developing and coordinating data models and file formats to facilitate collaboration and interoperability.

Managing Biomarker Data

The incorporation of biomarkers increases the variety, volume, and velocity of data in oncology clinical trials, especially if the biomarker is being used for both patient selection and monitoring of treatment response. This multitude of data presents challenges throughout the course of study execution, from site selection and study start up to data management and downstream analyses.

Sites must be trained and equipped to manage large quantities of samples and data. Sample management—from informed consent and sample collection to sample processing and result reporting—is critical. The informed consent process should be robust, as patients need to understand what their samples will be used for, how they will be stored and analyzed, and how the resulting data will be managed. With data being generated and stored by sites, central labs, logistics vendors, and specialty labs in disconnected locations and diverse formats, it is also essential to have a plan for linking and integrating such data in a centralized system.

Key stakeholders need to be able to view this centralized system for timely access to any and all data that are necessary for on-study decision-making. There are now numerous technologies available that are capable of integrating multiple disparate data sources into a single platform for analysis, enabling sponsors and CROs to get a broader picture of how patients are responding in real time and to make more informed treatment decisions.

Global trial coordination

Executing global biomarker trials can present various challenges due to the complexity of the study design, healthcare system and regulatory differences, and even cultural and societal factors. Recognizing these challenges and making a plan to address them is integral to success:

  • Differences in standard of care and screening can impact recruitment and retention. For instance, while NGS is part of the standard of care at many Western European sites, it has not yet been incorporated into the standard of care in certain Eastern European and Asia Pacific countries.
  • Ensuring compliance with varying regulatory frameworks and ethical guidelines across different countries or regions can be time-consuming.
  • Coordinating logistics  across different countries can be challenging, especially if the sample requires special handling or needs to be processed within a certain time period to ensure data quality.
  • Cultural and societal factors or norms can influence patient attitudes, beliefs, and willingness to participate in biomarker-guided trials. In particular, perception of privacy and level of trust in the healthcare system can affect enrollment and engagement.
  • Regulations concerning data privacy also differ around the world. For studies involving EU sites, compliance with the General Data Protection Regulation (GDPR) requires careful attention, especially with regard to transfer of personal data covered by this regulation to a location outside of the European Economic Alliance (EEA) . In the US, compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) is required. While many US states are implementing privacy laws that impose obligations similar to those under GDPR, to date, these state laws all contain an exception for personal information collected in the context of clinical trials. For trials that include digital biomarkers, the regulatory framework for data privacy and protection is still evolving. 

Partnering with an experienced CRO

At Premier Research, we combine our deep experience in oncology with expertise in biomarker-guided study design, regulatory strategy, and trial execution to help sponsors plan and conduct global precision medicine trials.

[1] Health IT Analytics. Data sharing, diversity key to accelerating precision medicine, March 23, 2021.