Clinical trials rely on speedy, reliable deliveries

South Africa is a popular choice for clinical trials because there is a large and diverse patient population with various disease profiles, including type 2 diabetes, heart conditions, cancer, TB, pneumonia and HIV, to name a few.

The delivery of investigational medicinal product (IMP) and clinical trial materials is extremely time critical and fraught with challenges.

Four phases in clinical trials

There are typically four phases involved in clinical trials. It can take between 10 to 15 years, or more in some cases, to complete the first three phases. The third phase generally involves patient sample testing, which is the phase in which express service providers are able to provide the most value.

Patient sample testing can vary in terms of number of participants from, typically, several hundred to several thousand per trial. Many of these trials involve collecting test samples from all over the country, including a small percentage from rural areas, to ensure a diversity of patients is being tested.

Each element of a clinical trial relies on some form of transport, from getting the test kit to the investigator sites, collecting the patient biological samples and ensuring they reach their destination within the specified period, to delivering medication to the investigator sites for patient dosage. As a result, transportation can account for a large percentage of the total cost of a trial.

Clinical trials typically involve the collection of biological substances collected directly from humans or animals, including but not limited to, excreta, blood and its components, tissue and tissue fluid swabs, body parts being transported for purposes such as research, diagnosis, investigational activities, disease treatment and prevention and the delivery of IMP medication and medical supplies such as syringes and test kits.

With biological samples, a 24-hour turnaround domestically and a 48-hour turnaround internationally is a standard requirement from point of collection to point of delivery, with a 24-hour leeway. After that the samples spoil, which could compromise the patient and trial.

The collection to delivery time frame is particularly challenging with samples that have to be transported from remote rural areas to overseas destinations, such as the UK, US, India or Europe, where a central laboratory is based to process and the samples and produce test results.

Any delay in collecting samples and getting them to their destination within the specified timeframe could result in having to retest the patient or, in some cases, a patient or multiple patients having to be dropped from the trial or result in the trial not being continued if there is not enough data for collection and analysis.

Typical delays

Typical factors that can cause delays include regulatory procedures, customs inspections, airline restrictions and non-compliance by patients or the investigator sites, which are doctors' establishments where patients are tested and medicated.

Some test samples have to be kept at an ambient temperature between zero and 30 degrees centigrade while being transported, while others must be kept refrigerated or frozen. Blood sample types vary but are predominantly of an ambient environment while being transported.

A smaller percentage of test samples are packed on dry ice or liquid nitrogen, which are classified as dangerous goods, and need to be very carefully handled, packaged and declared. Dry ice, which is the most commonly used coolant, has to be packed in breathable containers made of material such as polystyrene. This is because when dry ice is frozen it contracts and once sublimation starts, it expands and emits gas, which needs space in which to evaporate. If confined in a sealed container, pressure will build up and the container could explode. Another danger is that the evaporating gas absorbs oxygen, which could result in the suffocation of humans or animals occupying the same confined space on an aircraft. This means that biological samples packed on dry ice are generally not transported in the same cargo hold as livestock. In South Africa, only certain airlines are able to carry biological samples, and as a result, there are fewer flights to book them onto. This increases the risk on the samples and the margin for delays.

When transporting biological samples packed on dry ice by road, the cabin of the vehicle where the driver sits should be sealed off from the samples.

Accredited drivers

Drivers have to be IATA accredited and trained in the handling of dangerous goods. Among other things, they have to be trained to check that the goods have been packaged properly and labelled correctly before signing for them on collection.

The sequence of events of a trial typically begins with the pharmaceutical company selecting a country where a large number of people are suffering from the condition the trial is focused on. It will then select a laboratory to process the samples and provide the results, and will appoint a company to manage the trial and then recruit doctors that have the necessary expertise, who in turn will recruit patients to participate in the trial.

One or more parties involved in the clinical trial process will also partner with an express delivery provider to handle all the elements of the transportation process, as discussed previously, for the duration of the trial.

Investigator sites need training

Doctors recruited for trials are referred to as investigators. In order to be able to participate in trials they will undergo a rigorous selection and accreditation process and be registered with any number of potential regulatory bodies, such as the Medical Control Council for example. Potential test patients in turn will go through a rigorous screening process to qualify for recruitment and participation in the trial. For example, in terms of criteria such as having the required symptoms, perhaps only two to five out of 50 applicants at site level will ultimately be recruited.

Study coordinators and clinical trial specialists at the investigator sites typically have some form of a nursing background. They also have to be specially trained through training institutions that are accredited by the SA Civil Aviation Authority / IATA to pack and label the biological samples as the physical shipper. Among other things, they will receive explicit instructions on the difference between the packaging used for samples that need to be kept at an ambient temperature and that used for samples that are transported on dry ice.

Rural, cross border collections

Collecting biological samples from rural areas can be particularly challenging, because patients often have to travel long distances to get to the investigator testing sites. Many of these patients rely on public transport to get to the testing site. For some it can involve travelling across borders from neighbouring countries, such as Botswana, which could mean patients have to travel more than 100 kilometres or more each time. When travelling long distances to be tested, patients may need to get up at two or three am. They may have to switch taxis numerous times, walk several kilometres to get to the testing site and then sit and wait for some time, bearing in mind that they must not eat before being tested.

If a patient misses a test, he or she might not be able to be re-tested, continue with the trial and receive medication. Throughout the duration of the trial, participating patients will continue to be tested and medicated and their progress monitored.

When being tested periodically over a long period, participating patients may need to take time off work to travel. Trial periods vary with some being longer than others are and with terminal patients they could typically be treated until death.

The increasing level of interest in carrying out clinical trials in South Africa is evident in the fact that the volume of collections and deliveries in this area is increasing on average by at least 10% to 15% a year. These trials can lead to lives being saved and also prolong and improve the quality of the patients' lives by improving on the market drug being tested.