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Balance of Evidence- Selecting a central laboratory partner for a clinical trial

Article · March 2013

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Andrey Karelin Maxim Belotserkovskiy

PSI CRO AG PSI CRO AG
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ICT Lab Selection
Balance of Evidence
Selecting a central laboratory partner for a clinical trial is
too often based on subjective factors. But a more objective,
project-specific evaluation will help ensure the most
appropriate lab is picked
The use of central laboratories (CLs) as an independent
participant in clinical trials is a widespread practice,
particularly given the requirements of regulatory authorities
and study sponsors for high-quality, reliable laboratory data
and the difficulties faced by local labs in organising the
required tests in the country where the trial is performed
(1,2,3).
CLs provide services ranging from conducting laboratory
assessments and compiling lab test reports, to contracting
courier services for delivering lab kits and biosamples to and
from medical institutions where diagnostics and treatment of
patients takes place (4).
Subjective Decisions
Regardless of the important role of CLs in clinical trials – and
the often substantial cost involved – it tends to be subjective,
rather than objective, factors that influence the selection
of a particular lab partner. In interviews with more than 50
sponsors, four reasons were commonly cited:
●● “A good recommendation from a person we know”
●● “One of our colleagues worked with this laboratory”
●● “We know a good specialist in this laboratory”
●● “We had a positive experience with the laboratory
when working on a previous study”
Another common approach is a sponsor’s mandatory request
to use a specific CL with which it has worked before, in a kind
of ‘preferred provider’ concept. The problem with this concept
is the absence of guarantees that the chosen CL is the optimal
choice for the particular study.
Before a study starts, many sponsors perform project-
specific audits of pre-selected CLs. This approach is
favourable to the preferred provider route since it
provides an opportunity to obtain reliable and up-to-date
information about the lab. However, it requires time and
additional expense, as well as audits of several labs in order
to optimise the selection. In addition, a lab audit performed
by auditors who do not possess professional laboratory
knowledge will not guarantee the high performance of the
lab during the study. Furthermore, some consultants offer
services to select CLs for clinical trials, but there is often
a lack of appropriate criteria for ensuring objective and
competitive selection.
62 ICT l May 2013
A Karelin, M Belotserkovsky,
V Khokhlova and A Kumar
at PSI
One way to address these issues and ensure a more objective
selection of a CL is to use the algorithm set out in Figure 1 and
explained here.
Initial Contact
For the initial contact (Stage 1), CLs can be pre-selected using
a company’s database, references or even an internet search.
It is usually sufficient to contact three to five CLs but, as a
general rule, the more complex the tests required, the more
labs should be approached.
For a preliminary contact, a short request about the available
tests (with the indication of the study geomix) and general
interest in the study is sufficient. Such interest is generally
confirmed very quickly, so it is recommended that non-
replying CLs are not approached a second time as their lack
of response tends to imply a lack of interest in the project. It
takes no more than a week to gather initial information from
all labs.
CL Feedback
The second contact (Stage 2) is the most difficult and
demanding. A CL’s early readiness to participate in a study
may not necessarily prove to be the case further down
the line. It is important to obtain the CL’s feedback on, for
example, study design and logistics, the laboratory’s quality
systems and some study-specific questions. Standard forms
will enable all the necessary information to be collected in a
single step.
One suggestion is to use a project-specific pre-qualification
questionnaire and a general lab pre-qualification
questionnaire, which together contain about 30 questions
covering all aspects. Any laboratory that can act as a CL can
provide all the requested information quite quickly, within
two to three weeks.
Selecting a CL requires a cross-functional effort with
independent participation from a project manager, who
will oversee and approve the selection, as well as a lab
specialist and a quality assurance auditor, to request and
assess the information that comes in. It is recommended
to appoint a qualified lab specialist to coordinate
the process.
 Figure 1: Optimisation of central laboratory selection process

Stage 1 Project manager Laboratory expert QA manager

Initiation of lab
selection process Initial contact letter
(initial contacts)

Lab 1 Lab 2 Lab 3 Lab 4 Lab 5

Stage 2 Project manager Laboratory expert QA manager

Collection of the data
(secondary contacts) Study outline
QA questionnaire
Project-specific questionnaire

Lab 1 Lab 2 Lab 3

Completed questionnaires and accompanying documents

Quotas and proposals

Stage 3 Client Laboratory expert QA manager

Comparative data
Project manager Lab 1 Data collection sheet
analysis
Lab 2 Data collection sheet
Reporting of the lab Lab 3 Data collection sheet
selection results

Lab selection report:

Recommended lab
Back-up lab

Comparative Analysis The importance of different aspects of the evaluation may

When potential vendors send back completed
questionnaires, along with the copies of requested
documents and budget, the next step is to carry out a
comparative analysis of the collected information (Stage 3).
This can be done by creating a project-specific lab profile for
each CL that has expressed an interest. This form contains the
questions posed to the CL, its answers, and the comments of
the lab specialist and auditor.
change, depending on the lab assessment programme. For
example, if a standard safety panel is envisaged in the clinical
trial, the most important aspect is to evaluate quality systems
and IT, and the auditor should lead the process. On the other
hand, in the case of a complicated pharmacodynamic or
pharmacokinetic study, the main aspect is the professional
opinion of the lab specialist, especially when assessments are
related to validating a method or approach that is new for
the CL.

The CL’s capabilities can then be assessed using the simple
scale for each aspect of evaluation: acceptable (fully meets
the study specifications and regulatory requirements, with an
adequate financial proposal); partially acceptable (corrective
actions can be made during negotiations); or not acceptable.
Issues to be considered during the evaluation include:
● Quality systems
● Ability to meet protocol specifications
● Logistics
● Data management and IT services
● Additional services
● Budget and reliability of cost estimates
● Regulatory compliance
● Willingness to cooperate
● Previous experience (if available)
● Additional project-specific aspects
Project-Specific Profiles
An essential part of the profile involves evaluating the
adequacy of the CL’s costs. When comparing the budgets
proposed by CLs, it should be taken into account that the
main elements of the budget may be compiled and calculated
in different ways, so transparency of the calculations is the
major requirement.
While compiling a profile, the lab specialist may ask additional
questions and request clarificiations about the budget
and other provided information. Even if a CL completes
its questionnaires on time, this subsequent process of
communication between the CL representative and the
lab specialist will reflect the ability of a potential vendor, if
selected, to maintain communication with the sponsor at
the later stages of a trial. A lack of communication from a

www.samedanltd.com l ICT 63
 CL selection – at a glance
● Comparative analysis of several potential vendors’ proposals,
made on a competitive basis
● Impartial assessment through independent expert evaluation
of documents performed by qualified lab specialist and
auditor
● CL selection, based on the best combination of the following:
– Capability of a CL to comply with the protocol requirements
– Availability of a satisfactory quality control system in the
laboratory, including a set of regulatory documents
(licences, certificates, etc)
– Adequacy of the logistic solutions offered by the CL
(including terms of transportation of the biosamples
and proposed duration of their stability)
– Acceptability of the budget
– Satisfactory level of laboratory management, also proven
by previous cooperation
CL at this stage might bring the need to remove it from the
the list of potential vendors, since the inability to obtain
answers in a timely manner during a trial almost always has
a negative impact on the results. The time of the follow-up
communication must take no more than one month, which
includes obtaining all clarifications.
Final Choices
Based on these project-specific laboratory profiles, a final
document can be prepared that contains the comparative
evaluation and related scores for each CL’s ability to conduct
the trial, enabling the sponsor to choose the most appropriate
lab. It is also recommended to select a backup CL in case
any unresolvable problems arise during negotiations with
the favoured lab. The final choice should be agreed by the
dedicated lab specialist and auditor and then approved by the
project manager.
Most CLs that operate in the clinical research sector provide
lab test results of a similar quality. Likewise, their IT systems,
regulatory compliance documents and quality systems are
in most cases acceptable. However, logistics, budgets and
laboratory or project management, especially in terms of
communication and collaboration with the sponsor, can vary
dramatically. It tends to be these latter factors that have a key
role when making the final decision on vendor selection.
The ultimate decision should be made based on a balanced
assessment of all criteria. It should be noted that financial
proposals, while clearly very important, should not be given
inflated consideration during the selection process at the
expense of other aspects. In many cases, laboratories offering
overly favourable financial terms, when selected, present the
client with a number of bad surprises during the study.
Moving Forward
Using the process recommended here, the entire process of
selecting and approving a CL should take between four to
six weeks, depending on the planned scope and complexity
64 ICT l www.samedanltd.com
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of laboratory assessments and the sponsor’s specific
requirements, allowing the next step – contract negotiations
– to begin.
The approach should reduce subjective decision-making, help
ensure an appropriate and cost-efficient CL is appointed, and
minimise the likelihood of having to undertake the complex,
laborious and costly task of replacing an unsuitable lab
partner while a trial is in progress.
References
1. Clinical laboratory improvement amendment. Visit: www.cms.gov/
regulations-and-guidance/legislation/clia/index.html
2. CLIA-related Federal Register and Code of Federal Regulation
announcements. Visit: wwwn.cdc.gov/clia/docs/cms-2226-f.htm
3. ISO 15189: 2007: Medical laboratories – Particular requirements for
quality and competence
4. Leão Jr F, The local central lab model: With globalisation of trials
comes the difficulties of sample logistics. Enter the central laboratory
model, Applied Clinical Trials, April 2008
About the authors
Andrey Karelin PhD, DrSci (Biology), is
Director, Laboratory Support Services at PSI
CRO AG. He is a graduate of the Department
of Biology, Moscow State University. Before
joining PSI in 2001, he worked as the Head
of Laboratory at Shemyakin-Ovchinnikov
Institute of Bioorganic Chemistry.
Email: ???
Maxim Belotserkovsky MD, PhD, MBA, is
Head of Medical Affairs at PSI CRO AG.
He is a board-certified physician in internal
medicine, rheumatology, anesthesiology and
intensive care, nephrology and haemodialysis;
an Associate Professor of Pathological
Physiology; and a corresponding member of the Russian
Academy of Natural Science.
Email: ???
Veronika Khokhlova PhD is a Senior
Laboratory Specialist at PSI CRO AG. Before
being recruited by PSI in 2005, she worked
for more than 15 years as a Senior Research
Associate at the Russian Academy of
Science.
Email: ???
Akhil Kumar MD is a Medical Director at
PSI CRO AG. Previously, he worked for
MGI Pharma, also as a Medical Director,
and was an independent consultant. He is
board-certified in both medical oncology and
haematology in the US and is an Assistant
Professor of Medical Oncology.
Email: ???