Multi-Site Trials – The Logistical Challenge

Multi-site trials are becoming the norm as researchers widen their search to find new participants and gain crucial exposure to new markets. Operating a clinical trial in a different country and on a different continent can pose significant logistical challenges. Here’s how you can overcome them.

The meta-analysis of randomized controlled trials is considered to provide the ‘highest levels of evidence’^[1], with researchers and regulators suggesting that large-scale trials should be used as the basis for all future medical decision making. The gold standard of research requires significant levels of investment, with the identification, recruitment and retention of participants perhaps the biggest challenge facing trial organizers.^[2]

Multi-site trials offer significant benefits to clinical trial operators, exposing them to a greater number of potential participants, which can go some way to mitigating the recruitment risk.^[3] Multi-site trials offer clear benefits, but larger and more complex trials also pose significant logistical and sample management challenges. Overcoming these challenges is key, and by working with partners who can deliver global support – such as Therapak – you can add extra confidence to your trial logistics.

Standardized Approach

At the heart of the discussion is the challenge of consistency^[4], ensuring “not only the continuity of research data, but also quality of care and safety of participants on study.”^[5] Study managers need to navigate complex regulations and best practices which differ from country to country, including review and approval by national drug regulatory authorities (NDRAs) as well as recognized research ethics committees (REC).^[6]

To demonstrate trial consistency, managers need to ensure that equipment, tests, analysis and data presentation are all standardized. This is fundamental to the data integrity of your trial, and avoiding what David Burrow, Director of Scientific Investigations at the CDER of the FDA describes as “shades of gray” in global clinical trials data.^[7]

To achieve this, a rigorous methodology, a solid strategy and standardized testing kits and equipment are essential. Therapak provides customised testing kits anywhere in the world – and our partners MESM and EPL can support with clinical trial equipment and sample storage respectively. Having a strong approach to these key areas is fundamental to conducting a trustworthy trial that delivers results in which stakeholders, regulators and ultimately patients can have confidence and gain value.

While strategy, protocol and methodology can all be done at arm’s length, logistics are another matter. While trial managers can seek to develop new in-country supply networks, the risk of failure is too great for many. Instead, a growing number of trial managers prefer to work with a global network of suppliers like Therapak and MESM; reliable partners who provide logistics support to make your trial run smoothly.

Working together, equipment is selected, calibrated and delivered in time for your trial. Standardised test kits can be delivered around the world – with due consideration to local regulations and controls. This end-to-end trial management ensures that your multi-site clinical study runs successfully across the globe.

Sample Management

Sample management – our partner EPL Archives’ specialty – is considered one of the most challenging aspects of clinical study.^[8] As the complexity and scale of trials increases and more become multi-site, many trial operators are turning toward a centralized testing facility, where samples are delivered to one location for processing. Cost, transparency and oversight are all reasons for the shift, but there are risks. If the samples are compromised, through the testing process or during transit, then they are rendered worthless, potentially signalling the end of your trial.

These factors need to be considered at the study design stage. To guide you, the Global Bioanalysis Consortium (GBC) has developed five key best-practice principles for sample management:

1. Sampling procedures should be described in the protocol or within the laboratory manual, including the volume of the sample to be collected, the required anticoagulant, light sensitivity, collection and storage containers, and labelling with a unique identifier.
2. The correct procedures for processing and storing the samples after collection must be followed.
3. Chain of custody for the samples needs to be secure, typically maintained via paper and electronic data systems.
4. Pre- and post-analysis storage location and conditions must also be clearly defined at the analytical laboratory. The storage temperature of the samples must be traceable and controlled by monitoring and warning alerts.
5. At the end of the study, thoroughly document the samples’ disposal.

Avantor Clinical Services: The Local Approach

Trial managers need to consider many factors when undertaking multi-site trials; sample temperature and regulating it, appropriate pressure in transit, IATA regulations, domestic rules regarding the transportation of medical goods, and the risk of expiration of materials in transport.

The responsibility for transporting clinical samples from multiple trial sites and managing their storage is complex and demanding, but can be effectively managed by working with a network of trusted partners. Our partner, EPL Archives is experienced and has built a growing network of facilities able to store over 100 million research and manufacturing material assets – and never failed to return one. This is backed up by EPL Archive’s validated proprietary material management and environmental monitoring system, and specialized equipment to support clients in North America and Europe. The opening of the Avantor Services new purpose-built EPL Archives biorepository facility in Leesburg further expands our ability to store and preserve research and manufacturing materials, supporting trials across the world.

A successful trial is the combination of solid design, a great strategy and the right blend of personnel and partners. You need confidence that your suppliers will provide the end-to-end support – from trial design to data processing. The Avantor family of companies have years of experience supporting multi-site trials of all sizes, delivering the world-class support for studies that change lives.