In the early 1990s, the concept of the central laboratory was developed and implemented by laboratories delivering services
to major pharmaceutical companies. The goal was to consolidate the test results and data originating in different clinical
sites, which was previously analyzed in local labs. Bringing the samples to one single laboratory would avoid consolidation
of biased test results among different laboratories, all of which could be using different analytical platforms, kits, and
reference values.
This concept was first applied to clinical studies conducted in the United States. Soon after, the courier industry started
offering solutions for biologic sample transportation, which allowed the central lab concept to be applied globally.
Later, the concept of the affiliated laboratory was created. The affiliated laboratory covered geographic regions that had
difficulties exporting biologic samples. As a consequence, the central laboratory became more global and started to build
different types of associations with analytical laboratories in different parts of the world.
Nowadays, clinical trials are globalized and clinical sites are not just in the backyard anymore. Places that may sound exotic
but are rather well prepared for research appear in the site list of Phase II and III studies (like Coquimbo, Chile, and Belém
do Pará, Brazil) and perform according to Good Clinical Practice requirements. In parallel, logistics costs and constraints
are increasing, especially after September 11th. Logistic Issues
The increased project logistic costs referred to may, in some instances, be higher than the laboratory costs. Also, a considerable
number of samples are not able to reach the analytical facility under adequate conditions to be properly analyzed. The patient
recall for sample drawing may take up to one week, sometimes more, and represents a delay in the study schedule. Additionally,
this recall may negatively affect patient adherence.
Query solution and clinical site support processes usually are best dealt with by local teams and staff. Differences in language
and time zones between central labs and clinical sites may be problematic if dealt with from a distance.
Additionally, clinical site staff may be responsible for logistical tasks, though that is not exactly in their scope of expertise.
These tasks could include sample and invoice preparation, courier processe or dry ice providers. There also are difficulties
in shipping lab material to remote sites, which could increase study costs and cause logistic constraints. These logistic
constraints usually relate to moving samples and lab kits to central labs in reference countries, generally the United States
or Europe, which is forcing trial sponsors to consider new approaches regarding central laboratory services.
Considering that the analytical equipment and reagents most frequently used are available in several countries in the five
continents, a new concept is becoming more popular among the most innovative trial sponsors and global central labs: Partner
laboratory harmonization.
Harmonization: What does it mean?
Harmonization is a process led by the global central lab and its partners for specific projects. It aims to integrate comparable
results from different laboratories, avoiding possible bias generated by technical differences among them.
This process allows laboratories to exchange results instead of exchanging samples, thus overcoming obstacles previously mentioned
and representing fewer costs and less delays for the sponsor. Furthermore, it is also fair to say that access to new research
environments, with new sets of investigators and patient populations, will also be more easily achievable.
Depending on the level of harmonization that a group of labs decides to implement, they may reach a very close technical comparability
and can even be considered as a single entity by the trial sponsor, delivering the same service and results all over the world.
Of course, there are different levels of harmonization, which could involve internal and external parameters.
The four step process
Analytical platform harmonization. In terms of analytical platform harmonization, the first step is to compare the analytical equipment, methodologies, kits,
and reagents used in the laboratory test either in general or for the specific trial. If differences are found, they have
to be addressed through correlation tests. This will show that the results coming from different equipment can be considered
homogeneous and, therefore, can be consolidated in the study databank.
