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Operational and patient burden considerations for self-collection of blood specimens in clinical trials
Companies like Ancestry.com and 23andMe have helped make the self-collection of DNA via saliva relatively commonplace. In clinical trials self-collection of DNA via saliva and cheek swabs, as well as stool self-collection are also relatively common. This article focuses on devices that can potentially enable patients to collect their own blood in their homes for clinical trials. Through technological innovation there are several devices under development for potential self-collection of dried blood spot and liquid blood samples.
Over the past several years, and more recently due to the COVID-19 global pandemic, patient centric trial designs have accelerated specimen collection either at home via visiting nurses or phlebotomists, or at retail locations, like a pharmacy or a Quest Diagnostics patient service center.
Like home specimen collection, self-collection of specimens in clinical trials, sometimes referred to as patient-centric sampling, may make participation in clinical trials more convenient for patients. This paradigm involves sending specimen collection devices directly to patients, who then collect their own blood specimen and send it to a laboratory for testing. Technologies and solutions are under development to enable self-collection without the need of a phlebotomist or nurse home visit or a patient visit to an investigator site.
Self-collection of blood specimens in clinical trials starts out like specimen collection at investigator sites in that a protocol is developed and patient burden is strongly considered. Most of the time a central laboratory sets up a study database, and creates specimen collection kits that are study, investigator, and visit specific, and include requisitions and shipping materials. From there the processes diverge in that self-collection kits may be sent directly to a patient’s home instead of an investigator or home care specialist, and patients take on the process of collecting, potentially processing, and shipping samples back to the laboratory.
A variety of innovators are at various stages of blood self-collection device development. The information below is included to provide context for the reader and is not intended to be a comprehensive list or an endorsement of any specific device. For more information about individual devices, contact the manufacturers directly.
No finger prick required: Some devices require the use of a lancet and a finger prick. The following devices do not. The Tasso device is available in both dried blood spot and liquid collection formats. TAP, by Seventh Sense Biosystems, is available in a liquid collection format, and OneDrawTM from Drawbridge Health, is available in dried blood spot format.
Finger prick required: The following devices require a lancet, or have a self-contained lancet, and finger prick to collect via a dried blood spot format.
Protocol: Of course, it all starts with patients and an unmet medical need, but protocols must consider the current state of self-collection devices, including their approval status in the jurisdictions needed, and the most appropriate applications. For example, in a recent study the protocol called for a liver panel a few days after an infusion visit. The protocol included both home phlebotomy and the use of self-collection devices. Another recent study specified the use of a blood self-collection device to be used by patients for home collection of a specimen needed for HbA1c testing. Study design and protocol writing will need to be carefully considered to expand the use of self-collection in clinical trials where appropriate.
Collection approach: The specific device, and its regulatory status, the sample format (liquid or dried blood spot), approach to collection (lancet or device), location of collection (arm/thigh or finger), as well as the blood sample volumes required for the tests should be considered in developing the collection approach. The table below summarizes several of these attributes for the devices described earlier.
Assay development: Currently, most laboratory tests approved by regulatory authorities are primarily based on venous blood and not capillary blood used by the devices described above. We have found via correlation studies, that some analytes may require redefining specific reference ranges for capillary blood, serum, or plasma. From a clinical trial assay development perspective, pharmacokinetics (PK) and safety testing have emerged as target applications, but immunoassay and molecular tests are also being considered. There have been a considerable number of publications on PK testing via dried blood spot. As described above, one of the initial applications gaining traction is additional safety monitoring through the use of self-collection devices to increase sampling frequency without undue patient burden.
Device regulatory framework: Each of the devices are in a different state of readiness from a regulatory perspective. This is a dynamic landscape which must be assessed for each of the countries involved.
Kit building: Like traditional specimen collection kits, self-collection kits require visit and investigator information, air waybills and return boxes to facilitate return shipment. Barcoded labels will simplify processing at the destination laboratory.
Centrifugation: Some tests require centrifugation prior to shipment. Fortunately, small portable centrifuges, like the Sandstone Torq, and other potential innovations are under development and may be suitable for home use. Once available, consideration will need to be given to a centrifuge reutilization program, so that the right number of centrifuges are available at the right time for a study, to optimize cost and simplify logistics. Alternatively, work is ongoing to evaluate the impact of centrifugation at the lab instead of at the time of collection. It is likely that the results will vary by analyte.
Direct to patient: One option is to send the kit to the investigator to complete the demographic portion of the requisition and provide the device kits to patients. However, it may be preferable to have kits shipped directly to patients. Couriers should be chosen carefully to assure convenience of pick up time for patients. A shorter pick up time window is preferred by patients. Patients must also be counseled on any considerations about specimen stability and transit time from the point of collection.
Tests required: Laboratory tests require a minimum volume of blood, so the tests required by protocol will drive sample volume requirements, which in turn impacts the type and number of devices needed. Even with traditional blood collection in an office or clinic setting, limiting the required blood volume is a consideration in reducing patient burden. Self-collection may not be practical in all cases, particularly if the protocol requires a battery of tests with a need for high blood volumes.
Pain tolerance: Manufacturer pain tolerance studies indicate that venous and finger stick collections are more painful and may be less preferred to the more novel approaches described earlier. Also, it may not be practical for all patients to use a lancet for self-collection.
Collection time and complexity: At the time of writing this article, Tasso is the only manufacturer to include removable standard tubes for liquid capillary blood collection on their website, but Seventh Sense Biosystems is also developing a device, TAP II, with standard removable tubes. While collection times vary by patient and device, our experience with the Tasso Serum Separator Tube (SST) devices showed that it takes an average of five minutes to collect about 300ul of blood, with similar claims made by Seventh Sense Biosystems for their TAP device. Depending on the testing and sample processing requirements, such as centrifugation, the complexity and number of devices could become a barrier.
Centrifugation: The complexity of pre-analytical sample processing requirements must be carefully considered. For example, removal of a tube out of a device like the Tasso SST, letting it sit for 30 minutes and then placing it in a centrifuge, may be too difficult for some patients, and may require innovative approaches to assure compliance. Additional studies and innovation may be needed to reduce this burden.
Logistics: Direct to patient (DtP) kit delivery and pick up options, including pick up windows, availability of dry ice, and access to white glove services vary significantly by location. Initial forays into self-collection of blood specimens in clinical trials may aim to limit patient burden with simpler sampling and sample processing requirements.
Patient support: This new paradigm of self-collection will likely require extra patient support. For example;
Frozen shipments: Certain laboratory tests require samples to be frozen at lower temperatures than residential freezer units permit, and it may not be practical to ask patients to store blood samples in a residential home freezer for health and safety reasons. Innovative approaches are under consideration, including carefully timed courier visits.
We recently completed a comparison of a 12-analyte chemistry panel using a Tasso-SST self-collection device and a Sandstone portable centrifuge. The study, which is being summarized for publication, consisted of 24 consented subjects, who had venous samples collected via a phlebotomist and capillary samples collected via self-collection. Sample sets were tested on the Roche Cobas 8000/c702 for a 12- Analyte Chemistry Panel, consisting of Total Protein, Albumin, Glucose, Sodium, Potassium, Chloride, Magnesium, Calcium, Phosphorus, Total Bilirubin, ALT and Enzymatic Creatinine. Overall, good correlation was observed, and examples are shown below.
Blood self-collection devices are in various states of regulatory approval and their utility varies by the amount of blood they can collect, processing requirements by test, and the creation of tests validated to appropriate regulatory standards and guidelines. The cost of the devices vary, as does the potential cost of patient support and courier fees, but when considering the cost of a site visit or a home visit by a healthcare professional, the cost of self-collection of a blood specimen for certain applications appears favorable. Once devices are perfected and operational processes are solidified, self-collection devices should have a bright future in providing utility for decreasing patient burden in clinical trials and supporting decentralized trial designs.
Chuck Drucker is the Head of Decentralized Trial Solutions; Brian O’Dwyer is the CEO; Patrice Hugo, PhD, is the Chief Scientific Officer; Charlie Fix is the Global Director of Scientific Harmonization; Caroline Keane is the SVP of Global Head of Project Services; Guy Rachmuth, PhD, is the VP of Strategy & Corporate Development; all of Q2 Solutions