In this step, the intervention and lab requirements are finalised, by entering into an agreement with a laboratory (or several laboratories, if you’re dealing with multiple sites).

At this stage, handling procedures should be discussed and decided upon – for example, the timing of sample delivering and processing, storage, quality management, data capture, staff training, etc.

For further information or discussion with laboratory professionals, you can visit the laboratory area of The Global Health Network: http://www.globalhealthlaboratories.org.

Laboratory Requirements
Laboratory tests are used in clinical trials to diagnose disease or rule out other underlying disease that could affect the results of a trial. They are also used to assess the efficacy of a medication or to monitor the effect of the trial drug on patients. It is therefore important that samples are collected appropriately and correctly to avoid any false positives or negatives which may affect not just the patients on the study but also potential patients on whom the results of the study will apply.

There are a number of factors that could influence lab parameters and they include:
- The choice of lab assessments and how they will be measured
- Lab assessments and measurements
- One central vs. many local lab assessments (will depend on laboratory capacity and whether it is important to avoid variance. It may also be that one assay has to be undertaken in a specific lab because it is very specialised)
- Interpretation of lab results
- Quality Assurance and data validation

Lab Assessments and Measurements
The type and choice of lab assessments should be discussed as early as the development of the protocol. The lab assessments that will be investigated will depend on what the study is setting out to achieve. In the case of new products, or using existing drugs for a new indication, then biochemistry and haematology safety assessments are normally standard. Lab assessment may also occur at the start of the study to record the baseline situation. In malaria drug trials, for example, haemoglobin levels are measured before dosing and during follow-up.

Many studies do not have a laboratory component; this is often the case for pragmatic disease management trials. Observational, epidemiology studies frequently involve laboratory sampling because the sample is needed to determine presence and level of disease, particularly in infections.

The review of lab data may be included in the safety monitoring plan and reviewed by the Data Safety and Monitoring Board and possibly the trial steering committee, depending how important it is to the trial endpoints or safety concerns.

Other lab tests include Pharmacokinetics (PK), toxicity and biomarker tests. Lab tests are included in the schedule of assessments in the protocol while detailed instructions on processing the samples should be documented in the lab SOPs

Setting up the laboratory for a research study

Any clinical laboratory can take part in research; there is no need for a separate laboratory. Indeed it is normally preferable the laboratory performing the assays is part of the healthcare facility, as this prevents any capacity or development only benefiting the study. If a specific assay is complex and specialised then samples may need to be sent to another laboratory and here sample tracking and shipment needs carefully consideration.
The basic requirements for a research laboratory are as follows:

1. Standard Operating Procedures

These will describe how the samples should be stored, when samples should be taken and the time, the type of samples - serum or plasma, whether or not patients should be fasting prior to collecting the samples, etc. Also included in the SOPs are labelling, transporting, tracking and storage instructions. Each of these steps require a separate SOP.

2. Quality Management
Quality assurance is performed to ensure that the system for measuring lab parameters falls within the agreed scope defined by the institutions standard of procedure (SOP).
ICH GCP states that “Quality control should be applied to each stage of data handling...” and therefore it is imperative that quality systems are developed to achieve in-house processes as well as independent quality assurance audits to ensure data integrity and safeguard patient safety.

Quality assurance processes should be developed to ensure that:

- The analysis or evaluation of clinical trial samples are conducted in accordance with the principles of GCP, protocols and contracts or work agreements
- The samples are analysed according to the laboratory’s policies and SOPs.
- Data is recorded and reported accurately, legibly, completely and in a timely manner.
- Trial data is archived.
- Lab personnel are adequately qualified and trained to a level commensurate to their role. A record of their qualifications and relevant experience should also be maintained.

Regular audits should take place to ensure that lab procedures are still within the acceptable range and that appropriate documentation is stored appropriately.
Lab staff should also be aware that only those analysis required by the protocol should be analysed, otherwise it represents a protocol violation and could be unethical.
The laboratory specific version of GCP is Good Clinical Laboratory Practice (GCLP) and provides a practical guideline for lab samples which will be used in clinical studies. You can find the link to the GCLP guidelines here: http://www.who.int/tdr/publications/documents/gclp-web.pdf

3. Maintenance and Calibration of Equipment
All equipment used for analysing the research samples needs to have a maintenance record and if relevant a separate calibration chart. Specific equipment will require specific records to assure reliable and consistent performance. Fridges and freezers need a regular temperature record and an alarm and response plan if they fail.

4. Training and Staff
All laboratory staff need to have a training record to demonstrate their competence on all aspects of their role and in particular the assay they conduct. The GCP version for laboratories is called Good Clinical Laboratory Practice (GCLP) and it’s advisable to have a refresher course every year, just like GCP. Labs can find free GCLP courses on the Global Health Network here.

You can read an account of a Cameroonian laboratory which was built up from basic beginnings to become a centre of excellence here: http://globalhealthtrials.tghn.org/articles/clinical-research-laboratories-trials-global-health-central-africa/ - the article provides a practical overview of how training, infrastructure, layout, sustainability, and other issues were approached.

Logistics and Shipping of samples
Shipping samples may seem like a straight forward and less technical process but if done incorrectly could jeopardise the samples collected.
The first point to note in ensuring smooth process is labelling. The lab kits should be labelled before it is shipped to the investigative sites. As some assessments may be repetitive at various time points in the protocol, it can help minimise errors if the tubes for those assessments are batched together and labelled appropriately for those time points.

Typically, labels should include the protocol number, site identification and patient numbers. Where necessary the time and date of collection may be required on the labels. The labels should be of good quality so that they can adhere firmly to the tube, particularly if the samples need to be frozen.
It is now possible to have bar codes with all the necessary identifiers present on the tubes, but sites may still need to record the time and date of collection. Sufficient time will also need to be invested in site training to avoid any mix ups.

If samples are to be shipped internationally, it is important that the appropriate laws are followed. Shipping samples within a particular region such as the EU may be straight forward and less time consuming process as the countries within the region share a common market. Shipment outside an agreed market may however require completing a proforma invoice where details of the shipment will need to be declared up front.
Shipment is also normally be restricted to a few days before the weekend to avoid samples sitting in the holding bay at the end user’s site over the weekend; especially if they are cold shipments. Sites will need to be trained to ensure that they schedule their patients’ visits to allow for these shipping restrictions.
Ideally there should be extra kits for unscheduled visits or accidents that may inadvertently occur at sites. Lab companies will also need to be able to cope with site emergencies to avoid too many missing samples.

References

MHRA Guidance on the maintenance of regulatory compliance in laboratories that perform the analysis or evaluation of clinical trial samples. July 2009
http://www.mhra.gov.uk/home/groups/is- insp/documents/websiteresources/con051910.pdf

Clinical Laboratory data
http://content.karger.com/ProdukteDB/Katalogteile/isbn3_8055/_77/_24/spriet-02.pdf