A key and distinct characteristic of IVD clinical studies is that they are conducted on samples taken from study participants. Patient samples may still be used in other types of studies, for example, to show drug concentration in the blood during a pharmaceutical study; however, for IVD clinical studies, analysis of the patient sample is the source of the primary data set supporting your device’s clinical performance in a regulatory submission.
Due to the criticality of the patient samples, a sample management approach that clearly demonstrates appropriate sample handling as well as a well-documented audit trail is of the utmost importance. In an IVD clinical study, samples that are misplaced, mishandled, or otherwise invalidated will have an impact on timelines, budget, and data integrity – which could jeopardize your entire study.
Strategic Sample Management
Successful sample management starts early by clearly defining in the study protocol how you plan to maintain sample integrity. The more clearly defined and articulated practices that are in place supporting sample management, the better your chances are of being able to provide a complete, documented record of the sample journey and chain of custody (CoC).
All sample management strategies have three primary points during the sample’s journey where well-defined processes and parameters are needed:
- sample collection
- sample processing
- sample transportation and storage
The sample management strategies you decide on will vary based on several factors, including the target analyte, the sample type, and the intended use setting.
The sample management strategies you decide on will vary based on several factors, including the target analyte, the sample type, and the intended use setting. Due to the range of intended use settings for IVDs, there may be additional analytical testing requirements to support sample stability and collection parameters. IVDs also have a wide array of common sample types with differing collection, processing, and handling intricacies.
Beaufort has deep expertise in working with diagnostic sponsors from the early planning stages of your study to ensure that the choices you make will help ensure proper sample handling and study success.
Adapting to Use Settings
It is important to consider the intended use setting. Is this a point-of-care device where the turnaround time from sample collection to testing will be minimal? If so, additional analytical testing supporting analyte stability for the sample in ambient storage conditions may be required in order to ensure the sample is processed before any impact to integrity of the sample (and thus the data) occurs. Are you developing a home test in which the patient collects the sample then ships the sample for testing at a central lab? Then freeze/thaw data and sample shelf-life data may help guide shipping specifications, in addition to sample collection instructions for the home user. The IVD risk classification and intended regulatory pathway, as determined by the device’s intended user and intended use setting, can be used to inform decisions about the data needed to support sample management in the clinical study protocol.
Diverse Sample Types and Handling Requirements
A variety of sample types, such as nasal swabs, nasal wash, blood, and tissue, are used in IVD clinical studies. These samples may be collected prospectively or retrospectively or may be purchased from sample banks or well-characterized cohorts. Further, samples may be impacted by conditions such as hemolysis, lipemia, or bilirubin interference during collection. It is important for the protocol to clearly articulate the source of the samples as well as appropriate collection techniques and materials, including the quantity and quality of sample needed. Questions to consider addressing in your protocol could include:
- What transport media are acceptable?
- Will samples be collected under informed consent prospectively for the study or purchased from a sample bank?
- What size blood collection tubes should be utilized to collect the necessary blood volume for testing?
- How soon after collection should samples be processed before testing or shipment?
- Will a sample with hemolysis affect your analyte results?
As sample contamination could have major effects on test accuracy, precautions should be taken during sample collection to ensure samples remain free from contaminants. Samples that may be biohazardous will warrant extra precautions, and it is advisable for these to be well-documented in the protocol and emphasized during training.
Labeling Protocol Considerations
Proper specimen labeling at the point of collection is a critical process to define in your protocol. Misidentified or inadequately labeled samples are a major source of sample management failures, so having clearly communicated expectations for sample labels can help protect the integrity of your samples and data. A typical label would include the protocol number, a site and subject identifier, and a unique identifier for that sample.
In some cases, it is desirable to collect enough sample to divide into multiple aliquots that can be tested, shipped, and stored for future use. In this case, the label should indicate the aliquot number of the sample or if it is a paired sample (i.e., Swab 1 of 2). Handwritten labels are not advised. The labels should also be durable enough to withstand expected storage conditions. For example, labels should remain adhered at -80°C or colder if samples are to be stored in an ultra-freezer. Likewise, samples that might sit in an ice or water bath should be waterproof. It is important for study sites to be provided with appropriate sample collection materials (including sample labels), and all expectations regarding labeling and documentation of all samples and sample types should be emphasized and understood.
Aligning Site Capabilities with Protocols
The procedure for collecting samples should be clearly and comprehensively articulated in your protocol and part of study training. Regular communication with your sites will also increase protocol adherence, as will employing robust, frequent quality control processes.
Partners with IVD expertise are better equipped to comprehend the nuances of the IVD protocol and ensure that the documentation requirements are met….
Working with established sites with proven competence, as well as utilizing monitors that are experienced with the nuances and intricacies of IVD sample management, improves the sample integrity you can expect during your study. Partners with IVD expertise are better equipped to comprehend the nuances of the IVD protocol and ensure that the documentation requirements are met to provide traceability into the sample handling and chain of custody.
Depending on your intended use setting and your investigational product characteristics, sample processing could happen immediately upon collection, or samples could be sent to a central lab for evaluation. In addition, site capabilities, processes, and procedures must line up with protocol requirements.
Ensure that your clinical study testing sites have the proper equipment and that any equipment that requires calibration, validation, and/or preventative maintenance have defined processes for documenting that these steps have occurred and are available for monitoring review during the study. The timing and logistics of sample testing should be explained in the protocol and during study training, and operators must understand how to perform testing with the investigational device(s) as well as operate any equipment required for sample processing. Reasonable safety precautions when working with any biological material is always advisable, but for samples that are known to be or may be biohazardous, such as those used for infectious disease studies, proper biohazard precautions must be in place and the biohazard training for study personnel handling these materials documented.
Your protocol should define disposition of samples following processing or testing. If samples are to be discarded, their disposal must be documented. If sample retains are kept, their storage parameters should be made explicit in the protocol and storage conditions documented throughout the study. If samples are to be returned to a central laboratory or Sponsor for storage, shipping conditions should be outlined in the protocol and evidence kept as part of study documentation.
Optimizing Sample Storage and Shipping
As the sample is key to obtaining data in IVD studies, storage conditions that maintain analyte stability within the sample type and a well-documented chain of custody are paramount. At the outset of study planning, defined acceptance criteria should be established for factors affecting analyte stability such as sample collection and storage temperature, number of freeze/thaws, and time elapsed from sample collection to processing, testing and/or storage. Storage and shipping conditions during the conduct of the study need to align with the parameters contained in the protocol, and these conditions must be documented through various types of records including temperature logs, transit receipts, or records of the date and length of time each sample is removed from storage (for testing or shipping). Study sites should be able to always show the location and storage condition of all samples.
All sample handling must also be documented, as well as the condition of samples prior to shipping and upon receipt. In addition, it is important that any personnel responsible for sample collection, processing, handling, storage, or shipment be trained on the study and have a record of their qualifications, training, and responsibilities included in study documentation.
Managing the logistics of sample storage and shipping can be a challenge. Sites must ensure that there is an availability of storage space meeting protocol storage temperature and security requirements for the duration of the study. Any storage equipment (e.g., freezers or refrigerators) should be validated and have traceable, controllable temperature monitoring and a back-up system in the event of failure. Knowledge of shipping logistics and processes is essential, especially if the study requires same-day sample processing outside of the sample collection site. Local conditions may need to be taken into consideration during particularly cold or hot weather, as this may impact sample storage conditions during transit.
Partnering to Protect Your Sample Integrity
A comprehensive sample management plan involves meticulous oversight of the sample journey and documentation demonstrating that samples are handled in a manner that preserves their viability and adheres to the protocol. When samples are collected, processed, stored, or shipped incorrectly there is the greater potential for false or invalid results, damaging the integrity of the study. By considering sample management from the beginning of study design, the most effective and efficient sample handling procedures can be built into the protocol.
Leveraging Beaufort’s diagnostic expertise and team of experienced IVD clinical research professionals and established investigational sites, can ensure that your study’s sample management is streamlined, well-executed, and meet all regulatory requirements and all samples maintain their integrity throughout the entire sample management process.Learn More