The Impact of Biospecimens on Clinical Study Design

We perform therapeutic and diagnostic clinical trials to learn the safety and efficacy of drugs and tests in a clinical setting.  Typically, we think about the biospecimens in a clinical study in terms of operational requirements such as sample collection, processing, storage and analysis.  Our ability to obtain and test high quality patient samples is an important consideration during the design of clinical research programs and may significantly limit the questions that we can ask in trials. 

For example, our ability to develop drugs for precision medicine in diseases such as cancer depends on access to high quality samples.  The fundamental elements of a trial are the objectives--what questions we intend to address--and the endpoints--what will be measured to answer those questions.   Trials are also defined by the patient population or the inclusion and exclusion criteria determining who is enrolled.   Successful clinical studies require careful planning and design of the study protocol to ensure that the study is feasible and that we capture the lessons learned.  Often, endpoints rely on patient samples for laboratory testing. 

Patient enrollment may require rapid laboratory testing for a molecular or genetic alteration to meet the inclusion criteria.  Researchers also collect patient samples for long term storage for future analysis in the hope that advances in technologies and disease knowledge will open new opportunities.  These study endpoints require robust biospecimen planning during the early development of research programs all the way through to the medical writing of the study protocol.   Study planning is typically based upon experience and expertise.  However, the industry is more frequently utilizing best practices and data-driven analytics and modeling. These tools will improve our planning and preparations for biomarker-driven trials that require biospecimens.

Targeted therapeutics and drug candidates that will rely on patient laboratory test results are becoming common in oncology and other diseases.  Diseases are also being reclassified by molecular biomarkers and complex laboratory tests.  As a result, the biospecimen considerations that have been discussed in the ongoing Biospecimen Series at Mendelspod are becoming critical success factors for drug development. 

In the planning stages we often would like to target a small patient population who may greatly benefit from a new drug compared to the general population.  We then have to ask if we can identify, test and enroll those patients if the samples for testing are difficult to obtain or unstable for shipment and testing.  Similarly, we may have a novel drug with a new mechanism of action that promises to address a critical clinical need.  In this situation we are often limited by the test to certain sample types that may cause a great deal of patient inconvenience or duress.   Difficulties in obtaining  repeated tumor biopsies is one example that has resulted in the development of tests that rely on surrogate samples that may be obtained from the blood.  These considerations often restrict many of our options for study designs include choice of diseases, patient populations and regions or clinical sites. These restrictions also impact the patient journey in the trial. 

Trial protocols summarize the collection and use of samples in a table or schedule of events or assessments.  What may appear to be a simple table, ultimately impacts the patient experience and determines trial feasibility and success.  Researchers must balance the potential knowledge gained, time, cost and risk to maximize the benefit of the study to current and future patients.  Biospecimen planning is increasingly an important part of this equation.  The Mendelspod series Back to Basics: Improving Biospecimens supports a greater understanding of the challenges and opportunities for improving how we utilize critical patient samples.  These improvements will also enable more powerful clinical studies, addressing challenging clinical questions and advancing novel drugs and diagnostics.