Sample Collection – International Surgical Trials Toolkit

Tissue sample collection is a key component of many clinical trials, with clinical trial samples providing a valuable resource for research. Human tissue includes anything derived from a human being e.g. tissue, cells, plasma, urine, faeces etc.

In the UK, clinical trial tissue samples can be collected and used within the lifetime of a specific project, or they can be collected and stored for potential ethically approved research beyond the timeframe of a specific project.

There is significant amounts of legislation surrounding the collection, processing and analysis, storage, disposal, import and export, and transportation of tissue samples in clinical trials. Therefore the processes necessary to comply with each of these, must be established prior to the start of the trial. It is likely that there will be country-specific regulations and requirements relating to the use of human tissue in clinical trials, so it is recommended that these are considered early in the trial planning stage so to prevent delays at site set-up.

General Recommendations

Local Requirements

Logistical Considerations for Sample Collection

The rationale for the collection of tissue samples should be justified within the trial protocol.
It should be clear whether or not the collection of tissue samples is mandatory for a site to participate in the trial or if a site can opt-out of sample collection, or if tissue collection will only be done at selected centres. At sites where sample collection is taking place, will this be optional for patients?
Perform a feasibility assessment of sample collection for each collaborating site/country. If a particular number of samples are required, will this be achievable across participating sites who are able to provide tissue samples?
The costs associated with sample collection should be included in the grant application.

Quality Assurance of Sample Collection

To try to ensure quality assurance of the tissue samples collected as part of a trial protocol, a ‘Trial Samples Protocol’ should be agreed by the Trial Management Group. This should detail the requirements for collection, processing, storage, transport, data protection etc. If sample collection involves a deviation from standard of care at any sites, oversight measures should be put into place to quality assure the process. This may include training of site staff to collect/process/ prepare the samples or the production of training materials to standardise the sample pathway.

Shipping

Shipping requirements will depend on the type of tissue samples being collected, and the purpose of this. It may be that the samples have to be shipped in real time, or it may be possible to batch samples to send periodically. Adequate funding should be included within the grant application to cover the cost of shipping, and any specific packaging required to ship collected samples (and the subsequent return of residual material back to site if required).

Sample Tracking

A robust sample tracking pathway should be put into place. In most cases, tissue samples will be sent to a laboratory/biobank rather than directly to the main co-ordinating centre. Clear channels of communication will ensure the coordinating centre can confirm which samples are due and expected, and the receiving laboratory can confirm receipt of samples to allow the trial coordinating centre to chase any missing samples. It is recommended that there is a process in place to allow reporting of any issues with samples so these can be resolved with sites, in addition to sites being able to record reasons why samples may not have been sent.

Sample Custodian at the End of the Trial

The location for the storage of samples at the end of the clinical trial must be decided. This may include any unused sample material following analysis in the trial or samples collected to produce a research tissue bank. If the samples are to be stored in the UK, this must comply with the requirements of the Human Tissue Act.

Legislation

In the UK there is legislation concerning the collection, processing and analysis, storage, disposal, import and export, and transportation of tissue samples in clinical trials.

The country-specific legislation, guidelines and regulations must be considered for each of the collaborating countries and must be adhered to. As a result, different processes may need to be put into place for collaborating sites that differ in what they can participate in as regards sample collection; the trials office needs to be aware of these differences. If certain sites are unable to provide tissue samples, are there alternative options which may achieve the same aim?

A Material Transfer Agreement (MTA) must be put into place between any institutions which are transferring tissue. Collaborating sites may have multiple MTAs in place if the protocol mandates that different types of tissue samples are sent to different institutions. It is recommended where possible that the research agreement with sites incorporates the required material transfer clauses.

Trial Documentation

The Patient Information Sheet (PIS) and Informed Consent Form (ICF) must adhere to country-specific requirements for the collection, use, transport and storage of tissue samples in clinical trial research. The process of withdrawal for consent for storage and use of the samples and the data associated with them should be clearly detailed.
The PIS and ICF may need to be made country-specific to reflect any requirements.
The PIS, ICF and CRFs to be completed by patients for the collection of economic evaluation data, may need to be translated (and back translated).
Labelling of samples may need to be translated and language used may need to be adapted to meet country-specific any requirements.

To ensure implementation of sample collections at international sites, it is recommended a local feasibility assessment is undertaken at the time of the grant development to ensure adequate processes and resources are implemented/included within the trial.

Are the samples requested as per protocol routinely collected at the collaborating sites or is the tissue collection outside of standard practice?
- If the collection is not standard practice then consideration must be given to the feasibility of the tissue collection and the additional processes to be put into place at the site to ensure collection.
Must the samples be processed in a certain way in order to comply with the trial protocol? And, if so, does the collaborating site have the facilities to ensure this compliance?
- It should be considered if any of the steps in the sample pathway are time-dependent and if the site can accommodate the requirements.
Must the samples (both pre and post-processing) be stored in a defined way? And if so, can the collaborating site comply with the requirements?
Does the sample collection require specific equipment or materials? Are these available at site?
- If equipment is required specifically for the trial and cannot be provided by the site, this should be covered by the trial budget. If they are sourced in-country, it should be considered whether variations between materials bought in different countries may affect the sample collection, and the trial, in anyway.
Are there any special packaging considerations when samples are in transit?
- If specific packaging materials are required, these should be covered by the trial grant. It should be established whether sites have the resource to be able to follow packaging guidance.
Will participating sites require the return of any residual tissue following completion of the trial?