The advantages of working with a central laboratory for conducting clinical trials

Plain Language Summary

Clinical research and trials involve healthy and diseased people who volunteer to participate in the study. Clinical trials are performed by administering the investigational new drug (IND) to study participants. A significant number of study participants are recruited, and the trials usually involve more than one site. The trial subjects are closely monitored during the study. The participant samples are regularly collected and tested to evaluate the safety and efficacy of the IND. Clinical trials are generally carried out at multiple trial sites involving different medical establishments. Each trial site may be equipped with a laboratory to process the participant samples. However, to ensure the reliability and accuracy of the results generated from the clinical trials, it is essential to perform all the testing in a central laboratory rather than in the local laboratories located at different clinical trial sites.

Globally, public health emergencies have become increasingly frequent. This is evident from the emergence and reemergence of microbes including the most recently reemerging Mpox virus. The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) that resulted in the pandemic affected billions of people throughout the world. Despite achieving significant scientific and technological advances, COVID-19 pandemic accounted for millions of deaths. This is majorly attributed to the unavailability of therapeutic drugs and vaccines to treat and prevent the disease.

A similar scenario is being experienced with a few other microbes like the Ebola virus, the Dengue virus, the Chikungunya virus, the Nipah virus among others. Despite these microbes being discovered more than 50 years ago, there is not a breakthrough in the availability of drugs or vaccines to treat and prevent the infections.

The only possible solution for a majority of these public health related problems is clinical research. Clinical research is a research process that is undertaken to discover new drugs, vaccines or any medical devices and surgical intervention to successfully treat, manage and prevent diseases [1,2]. The process involves identification of drug candidates and evaluating their pharmacokinetic (PK) and pharmacodynamic (PD) properties. Clinical research involves a lengthy process associated with analyzing the safety and efficacy of new drug candidates. It includes different phases like the pre-clinical and the clinical phase. In the pre-clinical phase, the Investigational New Drug (IND) is tested for its PK and PD characteristics like absorption, dissemination, metabolism and elimination (ADME) properties [3]. Following a satisfactory result in the pre-clinical phase, the IND gets approval from the local and international regulatory authorities like the United States Food, Drug and Cosmetic Act (US-FDA) to carry out the clinical phase, which is called a clinical trial [4].

During clinical trials, the participants recruited in the study are prescribed the IND and are regularly followed-up [5,6]. Additionally, the participants are regularly evaluated for the effect of the IND on different organs of the body. The blood and other appropriate clinical samples are collected from the participants and analyzed. The participants are carefully evaluated for the potential adverse effects produced by the IND.

Given the comprehensive evaluation performed on the participants, that includes different components like the hematological, biochemical and other pathological indices, it is essential to have a central laboratory that handles all the testing requirements. Moreover, clinical trials may involve more than one clinical site wherein the participants are tested using the IND at different clinical trial sites. Therefore, it is essential to unify the sample processing that allows clinical trial investigators and other parties to analyze and interpret the data obtained in the study [7].

A central laboratory is an establishment that most tertiary care hospitals are equipped with, to handle general samples during patient treatment and management. The central laboratory functions to deliver the laboratory medicine aspect of the patient management that covers all the areas of pathological sciences including specialties like biochemistry, microbiology, hematology, histopathology, molecular pathology, toxicology, genetics and immunology. Laboratory medicine is a discipline that deals with qualitative and quantitative evaluation of the patients' samples either for the purpose of patient disease diagnosis or for research purposes [8].

However, a central laboratory associated with a clinical trial is different. In a clinical trial, the participants are evaluated for the effects of the drug on healthy and diseased persons who volunteered to participate in the study. Since the IND may produce adverse effects, careful evaluation of trial participants is essential to avert any serious adverse events that may result in morbidity and mortality.

Processing of the clinical trial related samples in a central laboratory ensures that all the samples are handled in a common laboratory, under one roof, without bias associated with laboratory testing instrument, the reagents, the testing methodologies and reporting mechanisms. Additionally, a central lab ensures improved understanding of the results including the reference values and universal measurement units. Furthermore, processing samples of trial participants from different clinical trial sites in a central laboratory ensures consistent results removing any bias that could ensue when such processing is carried out in the local labs at each clinical trial site.

Having a central laboratory reduces the cost associated with the establishment of local labs in the respective clinical sites. A central lab provides a common roof under which all the samples collected from different clinical trial sites are processed. The laboratory utilizes less manpower, and ensures the safety, method validation and maintenance of the quality. Additionally, the laboratory would have dedicated experts who can troubleshoot any problems that arise before, during and after analyzing the samples. The central labs ensure ease of data collection, analysis, interpretation and sharing of trial data. Despite increased turnaround time attributed to transportation delays, the data generated from the central labs are reliable and accurate.

The central laboratories may be equipped with advanced methodologies like automation, artificial intelligence and innovative data analytical software. Further, the central labs could be upgraded to use robotic software, a robotic process automation (RPA) that lessens the errors in clinical trial processes, speed-up the workflow and limits the burden on the personnel. Application of RPA has potential benefits in handling trial-related data [9].

The major drawbacks with the establishment and functioning of a central laboratory are requirement of efficient transport and storage of the samples collected from different clinical trial sites before being brought into the central laboratory for processing. The Centers for Disease Control and Prevention (CDC), Atlanta, USA, is in the process of framing newer guidelines making it difficult and needing a lot of effort to transport samples. This should be considered as a new challenge in establishing central labs.

Although the local laboratories function rapidly in processing the samples and generate quick results, they may be prone to bias. This is because the local labs at different clinical trial establishments may not be equipped with similar testing standards. Moreover, the local labs generally fail to provide high-end molecular testing. Not all local laboratories have access to certain tests that the clinical trials may require. Besides, setting up new assays is time-consuming and costly for local laboratories.

Some concerns associated with the functioning of local labs at the clinical trial sites include lack of automation, accreditation of multiple local labs, methodological difficulties to achieve uniformity of testing, lack of skilled technical staff and unavailability of dedicated consultants/specialists to troubleshoot problems.

The Clinical Laboratory Improvement Amendments (CLIA) act of 1988 governs the functioning of the local laboratories in the USA. However, the CLIA regulations apply to clinical laboratories involved in the human disease diagnosis, treatment and preventive health check-ups. The CDC in coordination with the Centers for Medical and Medicaid Services (CMS) and the US-FDA approve the CLIA program enabling the quality of clinical laboratories [10]. The CLIA guidelines specific to clinical trials and basic research are not available.

The trial site laboratories may be plagued with limitations as described in this communication. This could affect the quality and reliability of the clinical trial data. Despite some logistical and financial limitations, performing clinical trial associated laboratory testing in a central laboratory is recommended.

Financial disclosure

The author has no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.