Whether you are conducting a phase 3 clinical trial of a new therapy or looking for biomarkers, you will need to collect samples, and that leads to a number of questions. How do you collect the biosamples in such a way as to preserve their usefulness—maintain molecular integrity—for your specific (or unknown) downstream analyses and assays? How many samples will be needed, how many “collectors” will be involved, and how many locations? How long do the samples have to be preserved, and how will they be stored? And how will you manage the data?
Here are some basics to help with planning sample collection and to help make the process as cost-effective as possible.
1. It's All About Controlling Variation
Biospecimen-based research depends on controlling pre-analytical variability (previously discuss by my colleague Dr. Debra Barnes here), maintaining sample integrity, and on annotating the biosamples with the appropriate data. Collection kits not only assist in controlling variability, but can also serve as an ideal starting point for data collection.
Kits allow you to standardize the components used for collection, a major factor in controlling pre-analytical variation. Instructions for specimen collection, whether the sample is tissue excised during surgery or blood drawn into a tube, can be included to ensure best practices and any special requirements are followed. The supplies and instructions for shipping the specimens and processing them at the lab can be included as well, which further reduces variability.
2. Why Assemble Supplies Into Kits?
Given that many basic items such as tubes and swabs can be shipped in bulk to clinical sites, why use kits? There are advantages and disadvantages to both scenarios (Watch the video blog discussing this topic here).
Advantages to designing and assembling collection kits:
- Kits can include the return shipping supplies and air bills that specify the courier service, delivery time at the lab, and instructions regarding packing the samples. This ensures that samples arrive on time and in the correct condition to maintain their integrity.
- Kits allow better management of complexity, such as visit-specific sample collection schedules that involve unique supplies, collection of different patient samples at different time points, and specimen collection by field phlebotomists, whose “office” is an automobile and who work in unpredictable environments (patients homes).
- Kits help site staff better manage timed collections—everything is ready to go.
- Kits allow for differences in site capabilities.
- Supplies that are sealed in a box or bag are far less likely to be used for other purposes.
- Items can be pre-labeled with barcodes or Quick Response (QR) codes to link the sample to the patient.
- Kits allow features such as custom-molded foam forms to protect fragile items.
- Kit boxes can be printed with identifying logos and other information.
Disadvantages of using a pre-assembled kit:
- If a component is lost, damaged, or past expiration date, the entire kit may have to be discarded.
Advantages to simply stocking supplies in bulk:
- Depending on the study and supplies, bulk supply chain may take less time to set up.
- If an item is damaged, another is always available.
- Some supplies are so standard and well-stocked (needles, butterfly sets, gauze, bandages, tourniquets, etc.) that kits are simply not needed.
The downside of using bulk supplies:
- Managing bulk supplies require more experienced site personnel.
- Bulk supplies can require significantly more storage space.
- Standardization is lost.
- Having to compile individual items for collection, labeling, packaging, and shipping of specimens adds time and complexity to the collection process, potentially reducing compliance with best practices.
The combination approach:
Fisher BioServices often provides a combination of both kits and bulk supplies. For example, we:
- Assemble the pre-labeled collection tubes, cryovials, and transport tubes in the kit, but
- Provide the phlebotomy supplies (vacutainer holders, needles, alcohol swabs, bandages, and others) in bulk); or
- Provide limited bulk supplies as back-up to the kits, in case less common components are damaged.
Kits vs. bulk supplies and the clinical site:
- Clinical sites that are experienced with clinical trials and other research processes may be set up to manage bulk supplies.
- The flip side of this is that a busy site may have several trials in progress, and it may prove difficult for them to separate each trial and collection protocol.
- Sites with less experience may not have study management systems in place, and sending kits will reduce your risk.
3. Getting to the Actual Kit Design
Kit design begins with the study design. A kit vendor should work with you to analyze the study protocol and estimate enrollment and/or other factors and then create a forecast of needed supplies. This should include timing of component orders to manage expiration dates, as well as the production and shipping schedule. Beyond the protocol and study, the kit vendor should also have extensive relationships with suppliers and be able to advise on what components are expensive, what substitutes may be available, what components can be cheaply custom-made, and what components will best preserve the target analyte.
Following a high level overview (will the kit be used at a clinical site, or by field staff, or visiting phlebotomists at patient’s homes?), the protocol is then analyzed for the specifics:
- Number of sites?
- Number of participants/site?
- Number of visits/participant?
- Participant-specific and/or visit-specific kit needed?
- What samples will be collected at each visit?
- What supplies are needed for each sample?
- Labeling requirements?
- Need for post-collection shipping kits and air bills?
- Instructions for the clinical site staff or field phlebotomists?
- 2-, 3-, or 4-part collection/requisition forms?
Arranging the components:
A kit may be as simple as a few tubes in a zip-lock bag. However, kits containing dozens of items are not unusual, and the more complex the kit, the more critical the layout. A good overall design will minimize the possibility of damage and loss of components and also help ensure use of the right item at the right time. This is where the experience of the kit designer counts most: the overall layout of the package can make a significant difference in the efficiency of your sample and data collection and also promote compliance with correct procedure.
Items should be secured to prevent displacement and damage during shipping and handling, and the components arranged so that clinical staff need only reach for the next available item as they follow instructions. Items needed for a specific task should be organized together, and sub-kits, if used, should also be placed in the order needed (consider shrink-wrapping sub-kits for security as well as clarity). Labels should be pre-applied and components easily and quickly identifiable; staff should not have to sort through a box or squint at a label to be sure they have the correct item. Any non-standard instructions or item should be incorporated into the overall design in a careful and step-by-step manner. Include extra labels in patient-specific kits, as small pieces of paper are easily misplaced.
It is not unusual for patient samples to go to different locations after collection. The shipping supplies—gel packs, labels, air bills, and related items—should be pre-labeled to the extent possible and packaged to minimize error. Leave no room for confusion as to what sample goes where.
All of these considerations increase accuracy and efficiency, reduce errors, and help control variability. Most importantly, they also allow clinical staff to maintain their focus on the patient.
Will potential downstream assays include testing for heavy metals or other contaminants? Many items used in sample collection kits can have additives or carry contaminants that can interfere with certain target analytes.
Your vendor should be able to provide screening of each lot of the kit components for contaminants, store the approved supplies in a quarantined environment, track the supplies by lot, and generally ensure that samples are not contaminated by the containers and supplies used for collection. Many research organizations prefer to pre-screen kit components in-house or at an independent laboratory. Others do not, and these organizations should work with a vendor whose kit design personnel have the appropriate technical background and business relationships with independent specialized laboratories that can provide the needed screening.
Collection plus administration:
Download the eBook to access the entire content