The validity and utility of clinical data depends on the standardisation of treatment and patient monitoring, which requires ensuring that all necessary materials are provided to investigator sites (or patients and homecare nurses in a decentralised clinical trial (DCT) paradigm) and that all materials used in the administration of treatments and the collection of samples — from the experimental treatment to comparator or concomitant medications and ancillary supplies like syringes and blood collection kits — are consistent to limit any potentially confounding variables that might impact the data. Besides assembling the materials themselves, it is critical that they are appropriately labeled and combined into laboratory kits that are complete, well-organised, and properly targeted for temperature-controlled shipping and storage.
Designing Kits for Success
Efficient communication among all parties is essential to ensuring that clinical investigators have everything they need and that kits are organised in a workable manner. Clinical trials can be completely derailed by the absence of a single component, a lack of clarity in labelling, or errors in temperature-controlled logistics. Additionally, optimised kit designs can dramatically reduce shipping and storage costs.First, the purpose of the kit or kits must be firmly defined. This is a critical stage, as imprecision in the understanding shared among the sponsor, the kitting services provider, and sites or investigators can create minor disconnects that snowball into greater challenges as the trial progresses. Among the most important early decisions is whether the needs of the specific clinical trial protocol would be best served by combining all materials in a single kit or if, owing to temperature control and other concerns, it would be more appropriate to divide components into multiple kits. Materials, including the investigational medical product (IMP), comparator drugs, and ancillary supplies, are collected, laid out, and analysed, and a kitting plan is developed to determine which components are included in each kit and the order in which they will be used.
The design of the kit is critical to ensure that all necessary materials are available when needed and in the most practical and useful way to maximise both compliance to the clinical trial protocol and ease of use for investigators. A primary consideration is imagining how investigators and other staff at the clinical study site will handle all the materials in the kit once the kit is opened. Everything must be labeled and in its proper place, which requires a full understanding of how the materials will be used by investigators and in what order. Pre-labelling is performed by the kitting provider rather than requiring that of the site staff, which reduces risks and the chance of errors. For example, a booklet label is placed on a syringe or a blinding wrap for syringes, providing detailed instructions on how to use everything and in what sequence. The procedures must be precise enough to ensure that compliance is identical among different individual investigators or multiple sites when applicable. The last thing a study team wants is to procure blood samples from a cancer patient only to discover after subjecting a patient to sample collection that the sample must be repeated, because it was placed in the wrong tube or was not handled properly, including temperature excursions.
Kitting plans are usually developed in collaboration between the kitting provider and the sponsor, although input from the investigational site staff can be very valuable when possible. In some cases, such as at the Cleveland Clinic, clients are having physicians evaluate the kitting designs beforehand to share suggestions or comments. That step significantly enhances planning and ensures perfect execution of the trial protocols.
Once a kitting plan has been established, it becomes necessary to develop comprehensive procurement strategies to ensure that the clinical study has what it needs when it needs it, and that sufficient and consistent supply is available for each component for all patients. The last thing a sponsor wants to face is proposing a certain item, such as a special needle or syringe, only to discover that these items are in short supply or difficult to obtain. While a certain amount of flexibility of supply is possible under clinical trials protocols, it is essential that all stakeholders, at every step during the trial, minimise any possible variability in the treatment administered to patients and the manner in which clinical samples are obtained, transported, and stored to ensure that variability in data results from the treatment administered and the intrinsic differences among patients, rather than, for example, dosing differences caused by minor differences between two different syringe products, or even in some cases, different manufacturing lots of the same material.
Evolving Challenges
Over the past 10–15 years, sponsor companies conducting clinical trials were typically seeking a “study in a box,” or an all-in-one solution to lab kits. However, this universal solution had its limitations, particularly because of temperature constraints on drug products. A number of ancillary components are needed with the drug, including various sizes of needles, particularly in the case of biologics. While the experimental drug — and often comparator drugs — may require temperature-controlled shipping and storage, ancillary supplies do not; thus, including drug products and ancillary supplies in a single kit may substantially and unnecessarily drive up the costs of temperature-controlled shipping and storage.
Other types of kits are not necessarily related to the investigational medicinal product (IMP) itself and may include electronic equipment required for the study, such as a watch, blood pressure monitor, or a smartphone device used to monitor patient outcomes and collect study data. Laboratory kits are also becoming more commonplace as part of the clinical study materials, because of the need for individual blood or bodily fluid collection. In these cases, along with the ancillary supplies required for sample collection and the corresponding temperature-controlled materials, requisition forms to be used for the blood tests are included and shipped along with the specimens to the central labs for analysis. Everything is assembled in the kit for completeness and portability to ensure that samples are collected correctly, shipped safely and securely, and accompanied by all relevant documentation.
Beyond the IMP and the necessary ancillary supplies, many clinical trial kits also include other drug products. Later-stage trials typically include a comparator drug for one arm of the study, so that the outcomes of patients taking the IMP can be compared with the standard of care to investigate differences in effectiveness and safety. Additionally, many studies include concomitant medications along with an investigational product that go along with either the IMP or the primary comparator (or both). Procurement of these other drug products in the quantities and on the timelines needed for successful execution of clinical trials is itself a whole other complex challenge, since shortages or other complications in their supply can entirely disrupt a trial. There are clear pragmatic advantages to working with a kitting provider — like Yourway — that also provides robust sourcing of comparator and other drugs, which ensures that kits will be prepared on time and include these critical materials. Yourway procures and prepares these drugs, labels them for clinical use, and ensures proper packaging so these important drugs are available in the specific region of the world they are needed the most.
Kits for Direct-to-Patient Trials
As a result of the pandemic, there has been an increased movement toward DCTs, which has forced kitting designs to become more patient-centric. Under DCT paradigms, treatment administration, sample collection, and even some analyses are performed in the patient’s home, typically with the help of nursing networks, so direct-to-patient (DTP) and direct-from-patient (DFP) kits may include electronic scales and blood pressure monitors for each individual patient, which were never necessary when the patient traveled to the clinical study site instead of the other way around. Demand for a range of products at unforeseen quantities have increased on a global scale. Often, the kits must be not only specific to the trial but also visit- and patient-specific within that protocol. Homecare nurses have the added tasks of replenishing supplies, such as nitrile gloves, sanitiser, wipes, sharps containers, and masks. Procurement of PPE supplies has remained a complex challenge, particularly in some remote areas. In some cases, DTP models involved complete lab services, which included shipping centrifuges and portable ECG machines to patients’ homes.
Kit identification and blinding adds another dimension to the intricacy of clinical study perspectives with the decentralised DTP model. Consideration must be given to who actually sees what is in the kit, who opens it, whether it is fully blinded, or whether blinding is needed on the outside or the inside. For the purposes of blinding, it is also essentially to ensure that kits containing the IMP, the comparator drug, or placebos have equivalent weights.
The design of laboratory kits for DTP trials must also take into consideration the collection and reconciliation of materials, ranging from unused drug product (with special requirements for controlled or highly potent drug products, particularly when a trial is cancelled and reclamation by the site is not possible) to sharps and recyclable materials. This is another area in which coordination between the kitting and DTP distribution provider is critical, and uniting these services under one provider creates significant synergies.
Kitting Services, Performed Yourway
Some companies are best at the transportation component, while others excel in packaging, Yourway excels in both to reduce risks, minimise costs, and eliminate vulnerabilities. As a result of the pandemic, competitor companies who specialised in kitting could not perform all the necessary kitting services and had to turn clinical studies away. Yourway stepped up to the challenge to provide immediate solutions. Yourway set up relationships and purchasing agreements with multiple companies, including B. Braun, BD, Greiner, and others, so that it could make purchases directly rather than through a wholesaler, providing more confidence in actually obtaining the kit supplies.
Yourway is truly a one-stop shop for the entire kitting process. Our teams emphasise comprehensive and thoughtful design, procurement at the front end, labelling, and open communication with the sponsor, clinical investigators, and suppliers. Other services that Yourway offers, including importing, exporting, storage, distribution, returns, reclamation, and DTP services, all intersect with kitting, giving us a complete understanding of all the relevant considerations and allowing us to provide the next level of services under our integrated offering.