Sample processing can yield invaluable information for clinical trial success. However, obtaining this information can be an extremely time-consuming and expensive process. Samples can produce pharmacokinetic, pharmacodynamic, biomarker, and immunogenicity information vital to clinical trials.
Enhancing the laboratory procedures to optimize sample collection can make the difference between clinical trial success and failure.
What Is Sample Processing?
Sample processing is the practice of analyzing a sample, such as blood, urine, or other biological material, and obtaining some form of useful clinical information. This could include a cellular biomarker, pharmacokinetic parameter, or even pharmacodynamic endpoint.
Despite seeming straightforward, sample processing can become extremely intricate depending on the goals of the clinical trial and the type and quantity of processing required.
Modern research has exponentially increased the demand for efficient and accurate sample processing. Historically, trials were much smaller, and fewer samples were processed; the evolution of sampling proficiency has revolutionized clinical trials and increased the demand for sample processing dramatically.
Nowadays, clinical trial complexity demands laboratories to process large batches of samples that can take hours each, not to mention the required laboratory personnel training time for unique processing techniques employed in some trials.
How Can We Optimize Sample Processing?
There are many strategies to streamline and enhance sample processing efficiency and techniques. Below we will discuss a few of the more common approaches to sampling processing optimization:
Improving the Supply Chain
Many times, neither the study sponsor nor clinical trial sites know all the steps in a clinical trial’s supply chain. Sometimes just one or two steps can take most of the processing time. Understandably, identifying these steps in advance can mitigate some of the time and money lost in establishing the logistics of a clinical trial.
There are additional early logistical concerns that must be addressed as well. Handling the sample can be more difficult than it seems but can be essential to collect it properly. Processing steps and shipping conditions can affect a sample’s integrity and should be accounted for.
Depending on the purpose of the sample, efficiency can affect the turnaround time of other study steps, such as deciding if a patient meets inclusion or exclusion criteria.
Educating Laboratory Personnel
Laboratory personnel at clinical trial sites around the world are as essential members of the study team as the investigators themselves. Their knowledge and expertise are invaluable resources, yet sometimes a trial’s specific sample processing requirement can necessitate additional education.
Study team consultation can be beneficial by outlining the expectations for each laboratory. For example, some studies require the preparation of specimen aliquots with unique handling in sterile environments. This can involve intricate techniques to combine sterility with appropriate specimen handling.
Other laboratory concerns can be implementing specimen centrifugation and utilization of bar code technology. While most laboratories use bar codes, some study protocols have study-specific barcodes that should be distinguishable from site-specific barcodes.
Sample storage is another huge concern for laboratory personnel. Ideally, samples should be inventoried and stored under proper conditions. The right storage technique varies depending on the sample.
These variances could include refrigeration, non-cycling freezer space, or under ultra-cold, -80°C conditions. In addition, samples should also have enough storage space allotted for the entirety of the trial.
Utilizing Pilot Studies
Pilot studies are smaller, introductory studies utilized in clinical research to obtain early information with the purpose of further directing larger, future clinical trials. They can be performed for a variety of reasons, such as testing a new intervention in a smaller sample of patients or conducting a smaller version of a proposed larger clinical trial to prepare for the future.
In the case of sample processing improvement, pilot studies can be used to train laboratory personnel how to process a new type of sample, validate current laboratory equipment and procedures, or even gain logistical information regarding a realistic turnaround time for sampling processes in the real-world setting.
Establishing Proper Test Parameters and Test Validation
Sample processing means nothing if the tests being utilized are not properly evaluated in the context of the clinical trials. Test efficiency, sensitivity, and specificity can differentiate the proper test from an inappropriate one.
Many laboratories have the capability of running culture and enzyme immunoassay tests. These tests have the benefit of being widely utilized, meaning the supplies and personnel required to run them are readily available. Additionally, their results can be generalized in comparison to other commonly run culture and enzyme-based tests.
Alternatively, some laboratories have access to molecular assays that maintain strong sensitivity and specificity. While molecular analysis can be even more useful in some instances of sample processing, specific tests for less common analytes are often laboratory-developed.
These tests can be time-intensive to set up and will require even more time to validate while training personnel to perform them.
In addition to internal laboratory considerations, there are generally regulatory requirements from the FDA regarding testing for use in clinical trials. The Clinical Laboratory Improvement Amendments (CLIA) require laboratories to essentially self-assess to ensure accurate and precise test results.
These federal regulations necessitate laboratories to implement and document performance specifications, adding another layer of complexity and consideration.
CLIA certification requires laboratories to report information such as analyte reference ranges and sensitivity and specificity. When outsourcing sample processing to a clinical research organization (CRO), adhering to CLIA certifications is an essential qualification. It may help avoid any unforeseen issues with the clinical trial.
Validation Procedures
The importance of laboratory validation can be widespread and complex. Specific parameters in laboratory tests must be continuously checked, even throughout the course of a trial, to ensure accurate and meaningful test results are obtained.
For many tests, after proper analysis templates have been established, reproducibility tests must be performed. Decisions such as the right reagents, buffers, test stimulus, and culture medium’s type or duration are finalized.
Once accuracy, reference ranges, sensitivity, and specificity, if applicable, have been established, the test process must then be transferred to each clinical site in which it will be performed.
Sample processing techniques can sometimes be very challenging to transfer to different clinical sites depending on each site’s laboratory capabilities, personnel, and overall setup. The study protocol, if done correctly, should dictate exactly what the responsibilities are for each clinical site in terms of the testing required.
However, considerations must be made regarding training the on-site laboratory staff, what conditions the test should be performed under, and any other protocol-specific criteria. The logistics can be overwhelming, to say the least.
There are additional test considerations besides logistical concerns. For example, deciding the proper test tube reagent can sometimes incur a practice difference between laboratory sites which can call for additional trial education from the study team. Small differences can have large downstream effects when it comes to accuracy in sample processing.
When to Use a Clinical Research Organization
CROs can be an invaluable asset to a study sponsor’s clinical trial effort. When it comes down to organizing sample processing, CROs are often well-networked with years of experience globally to make sure a laboratory is equipped to run any test required of them.
Sometimes, CROs such as iProcess Global Research, Inc. has in-house laboratory capabilities, further providing convenience and efficiency for a clinical trial. IProcess is CLIA certified and capable of infectious disease and Next Genome Sequencing. It is easy to request a quote to get any project started.
CROs can help consult with study sponsors to get a better idea for a study design that will produce accurate sampling and do so efficiently and as affordably as possible. Consultation not only helps sponsors, but it can assist laboratory personnel to make decisions, such as what vacutainer is appropriate for sample storage.
Sampling expertise is a critical component of any successful clinical trial.
While utilizing a CRO can incur upfront costs and fees for a clinical trial effort, the support and confidence it can provide can certainly be worth the expense. At iProcess, you can expect to work with a well-connected, experienced, and trusted supplier of biospecimens and consultant for any clinical trial aspiration.
Sources:
Design, Data Analysis, and Sampling Techniques for Clinical Research | PMC
Sample Collection, Processing, and Storage | PMC
Biological Sample Collection and processing for Molecular Epidemiological Studies | PMC
