Secondary use of samples and data

Background

What is meant by primary use and secondary use / further processing of samples and data collected in the framework of a research project?

Primary use = the use for which the samples/data were collected, i.e. to meet the purpose of a research project. Here the data collected is clearly linked to the objectives of the study.

Secondary use (or further processing) = other use, for a different purpose, not immediately related to the purpose of the primary research project.

A research project and a collection project are two different types of projects

Collection project = project aiming at collecting tissue and/or fluid samples and some associated data from sick or healthy participants without a defined research purpose.

A distinction should be made between submissions for opinion to the CNER which concern research projects on the one hand, and collection projects dedicated to supplying/serving one or more research projects (samples and associated data = biobanking) whose purposes are not yet clearly defined.

In a collection project, the use of samples and associated data to feed third party research projects is the primary use of these samples and data, as this is the purpose of the collection. Some of these research projects may already be defined when the collection project is envisaged, and others may not. But the implementation of a biobank cannot be an end in itself, as the objective of data valorisation would necessarily be too vague.

It is therefore logical that the collection project should be submitted to the CNER first, and that the research projects that will use the collected samples and data should be submitted for opinion separately, after the CNER has issued a favourable opinion for the collection. Therefore, a research project "with an open collection design" behind it cannot be presented and submitted to the CNER for opinion.

For these two types of projects, which are conceptually very different, the CNER publishes separate ICF recommendations and templates.

Note: The abbreviation "ICF" is often used in our field to refer indistinctly to the subject information sheet (SIS) and the informed consent form (ICF) all in one, even though the ICF is strictly speaking only the consent form.

Legal basis for secondary use of samples and data

As we were well reminded in our survey of other EU countries, the legal bases for secondary use of samples and data are not the same.

Regarding secondary use of samples for health research purposes: 

In Luxembourg there is unfortunately no other, more precise legal basis than the 2018 Hospital Law, and its Article 27 (1) in particular, which states that "Aucun essai, étude ou expérimentation clinique ne peut être pratiqué sur l'être humain en vue du développement des connaissances biologiques ou médicales sans autorisation préalable du ministre, les avis de la Direction de la santé et du Comité national d’éthique de recherche ayant été demandés au préalable."

The absence of specific legislation on secondary use in Luxembourg means that the general - European - legal framework for data protection must be used. Indeed, the only existing regulation that clearly addresses the subject of secondary uses is the RGPD, which the CNER applies. The most relevant criteria of the GDPR to be respected are:

-          legal precision (of the purpose of the data processing),

-          consent of the fundamental rights holder, and

-          proportionality, of which the data minimisation principle is an important element. 

Regarding secondary uses of data (also called "further processing") for health research purposes: 

At European level: GDPR (Regulation (EU) 2016/679)

• see in particular Article 9 ("Processing of special categories of personal data") and Article 89 ("Safeguards and derogations relating to processing for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes")

At Luxembourg level: Law of 1 August 2018 on the organisation of the National Commission for Data Protection and implementation of Regulation (EU) 2016/679

• See in particular "Chapitre 2 -Traitement à des fins de recherche scientifique ou historique ou à des fins statistiques", and its Articles 63, 64 and 65, where the organisational aspects for the implementation of Article 9 of the GDPR are further specified.

Recommendations for the secondary use for a new research project of samples and/or data that have been collected in a first research project

General comment on these recommendations:

In order to issue its recommendations, the CNER first conducted a dedicated survey within the European Network of Research Ethics Committees (EUREC).

Further explanation of each recommendation:

RECOMMeNDATION No 1: SYSTEMATIC SUBMISSION for opinion to the cner of PROJECTS for secondary use OF SAMPLES AND/OR DATA FOR SUBSEQUENT RESEARCH PROJECTS

Note:

As in Germany, Switzerland, Belgium, Cyprus, Italy and Portugal, projects for secondary use of samples and/or data for further research projects are systematically submitted to the competent ethics committee for opinion.

RECOMMENDATION No 2: PROVIDE A SEPARATE CONSENT FORM TO ACCEPT SECONDARY USES OF DATA AND/OR SAMPLES COLLECTED AS PART OF THE PRIMARY RESEARCH PROJECT

Notes:

In Luxembourg, the CNER recommends in all cases a consent form dedicated to secondary uses, well separated from the ICF of the primary study.

In case the secondary use project is a project in the same field as the primary study, and the CNER issues a favourable opinion for this secondary project, the patient/participant should not be contacted again to ask for a new consent.

For secondary use projects outside the scope of the primary study, not only is a positive opinion from the CNER required, but the patient/participant must also be contacted again and sign a new consent form for the new study. This implies that he/she has accepted, in the ICF of the primary study in which the samples/data were collected, the option to be recontacted to participate in other research projects.

RECOMMENDATION No 3: REFUSAL OF SECONDARY USES DOES NOT PRECLUDE PARTICIPATION IN THE PRIMARY RESEARCH PROJECT AND THIS MUST BE CLEARLY STATED IN THE PRIMARY RESEARCH PROJECT'S INFORMATION SHEET AND CONSENT FORM.

RECOMMENDATION No 4: IN PROJECTS WHERE SECONDARY USES ARE PLANNED, OBLIGATION TO INFORM PARTICIPANTS (WHO HAVE AGREED TO SECONDARY USES) OF WHAT HAS BEEN DONE WITH THE SAMPLES AND DATA. THIS INFORMATION CAN BE COMMUNICATED VIA NEWSLETTERS, INFORMATION CAMPAIGNS, OR THE PRIMARY PROJECT WEBSITE.

Note:

If the "website" option is chosen, this implies that the participant should be informed of the existence of the website in the primary study information sheet. The newsletters/information campaign/websites also serve as a reminder that withdrawal of consent is possible at any time.

RECOMMENDATION No 5: FAVOUR THE ANONYMISATION OF SAMPLES AND/OR DATA BEFORE TRANSMISSION TO THE PRINCIPAL INVESTIGATOR (PI) of the SECONDARY STUDY  (IF PI IS NOT THE SAME), AND IN CASE OF TRANSFER OUTSIDE THE EU

Note:

Applying Article 89 of the GDPR to the issue of secondary uses of research data for secondary research projects, it follows that, whenever the secondary research project can be carried out on anonymised rather than pseudonymised data, the data to be transmitted by the primary study PI to the secondary study PI should be anonymised before transmission.

Of course, this recommendation requires consideration if the primary research (with pseudonymised data) involves the possibility of incidental findings and that there is also the possibility of incidental findings in the project making secondary use of the data. Anonymisation when transferring the data to the secondary study PI would mean that the patient could no longer be traced in the event of incidental findings. Hence the choice of the word "favour" in the recommendation, as anonymisation should not have negative consequences for the patient.

RECOMMENDATION NR 6: IN THE CONSENT FORM FOR SECONDARY USES, PROVIDE A BASIC INTRODUCTION AND LIMIT THE CONSENT OPTIONS AS DESCRIBED BELOW:

Basic introduction content:

• describe the primary use foreseen by the primary study and explain what a secondary use is, i.e. a re-use of samples and/or data, for another research project, in this case limited to the same research area as the primary study;
• remind that consent to secondary uses of one's samples and/or data for other studies is voluntary, and that refusal of such secondary uses does not lead to exclusion from the primary study;
• specify how long the samples and data will be stored and may be subject to secondary uses if the person has consented;
• explain that withdrawal of consent for secondary uses is only possible for samples and data that have not yet been re-used, while also explaining why (e.g. because it would compromise the study, or is no longer possible if the data have already been anonymised/aggregated);
• remind that if they consent to secondary analyses of their samples, incidental findings are possible and that their expressed choice about sharing these with them or their relatives in the primary ICF will be respected. If the primary study ICF did not address this issue because there was no possibility of incidental findings in the primary study, a checkbox for this purpose should be added in this ICF dedicated to secondary uses (see checkbox for proposal No 4. in the tables that follow);
• specify that secondary uses may involve public or commercial/private partners but never include the sale of samples or data;
• specify where the participant can be informed of the secondary use projects (e.g. primary study website, ...); 
• explain that the consent options presented in the document differentiate secondary uses according to:
  • whether the investigator remains the same or not,
  • whether data or samples are involved, 
  • whether or not the planned analyses of the samples include genetic analyses.
• remind what is meant by pseudonymisation and anonymisation, as should normally have been done in the primary study information sheet;
• explain that in case of transfer of pseudonymised samples / data outside the European Union, the applicable data protection legislation may be less strict, and, if applicable, explain to the participant that they must give their explicit consent for this transfer. Also explain that agreements between the different partners will however be put in place to ensure a data protection level that is at least equivalent. Note: the transfer of data/samples in an anonymised form is to be encouraged;
• certify to the participant that their data will be protected in accordance with Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of individuals with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (hereinafter: "General Data Protection Regulation"), respectively the law of 1 August 2018 on the organisation of the National Commission for Data Protection and the general data protection regime (if the project is exclusively Luxembourgish) and more particularly articles 63 to 65 of this law;
• mention the contact details of the DPO of the primary study;
• We also suggest that you mention all the rights of the persons concerned with regard to the protection of personal data, for example in this way:

"You have the right to request from the controller access to, rectification or erasure of personal data, or a restriction of processing; you have the right to object to processing and the right to data portability under the conditions set out in Articles 15 to 21 of the General Data Protection Regulation. If you consider that the processing of your data constitutes a breach of the General Data Protection Regulation, you may lodge a complaint with the National Commission for Data Protection (CNPD)."

In the ICF for secondary uses, the following two tables with the different consent options must be included:

SECONDARY USES OF SAMPLES AND/OR DATA BY THE SAME INVESTIGATOR / RESEARCH TEAM / INSTITUTION:

SECONDARY USES OF SAMPLES AND/OR DATA BY OTHER RESEARCHERS:

CNER secondary uses procedure scheme