An update on the national general informed consent: what is the status quo of implementation at Swiss university hospitals?

The general consent, what are we talking about?

In personalised medicine, the use of health-related data and samples from large patient populations have become an important resource for medical research (Godard et al, Eur J Human Genet 2003, 11:88-122). Many countries have established infrastructures for large biobanks and health registries. Among the best known are the UK Biobank, which recruited 500,000 individuals between 2006 and 2010; the Estonian Genome project; the International Agency for Research on Cancer Biobank ; and several US biobanks. One of the most important characteristics of such collections is that samples and data are gathered for long-term future use and not just for a single project (Elger and Caplan, EMBO Reports 2006, 7:661-666). These collections offer new opportunities for research, but the management of this data also raises new challenges, in particular regarding the management of the IC process.

According to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), Good Clinical Practice (GCP) defines informed consent (IC) “a process by which a subject voluntarily confirms his willingness to participate in a particular trial, after having been informed of all aspects of the trial that are relevant to the subject’s decision to participate. IC is documented by means of a written signed and dated IC form.”

It is clear that it is difficult, if not impossible, to obtain comprehensive IC for future research projects that are not yet specified, such as in the case of research conducted at prospective biobanks. This has led to the development of alternative IC approaches, including:

A specific consent, which requires donors to be recontacted for each future study;

B tiered consent, for which donors check the kinds of research for which their biospecimens may be used in the future;

C dynamic consent, which engages donors on an iterative basis;

D blanket consent, which involves no restrictions at all for future use of donated biospecimens; and

E General Consent (GC), where donors can actively consent once for the current study and all future research involving the general use of their samples and information (Master Z et al, Eur J Hum Genet 2015, 23:569-74).

By far the most common model used today is the GC. It is considered acceptable and supported by several european countries, including Switzerland. However, GC should not be confused with open or blanket consent. Granting a GC means consenting to a framework for future research of certain types only. Key components of a GC include: the ethical review of each specific research project by an independent ethics committee, as well as the participants’ right to withdraw their consent at any time.

The legal basis of the GC in Switzerland: a complex and unique framework

In Switzerland, under certain conditions, the Human Research Act (HRA) and the Human Research Ordinance (HRO), which came into force in 2014, allow the use of GC for further use of biological material and health-related personal data for research projects to be specified only in the future.

The law provides different rules, depending on the type of data (genetic or non-genetic) and on the possibility of establishing a link with the data subject and the biological material (anonymised, coded, or uncoded). Table 1 below provides a summary of these rules as set out in the HRA and HRO. As a basic principle, GC is sufficient for all research projects, except for those using uncoded biological material or uncoded genetic health-related personal data (HRA, art. 32, par. 2).

Reaching a harmonised GC at the Swiss national level: a short history

The idea of reaching a GC for Switzerland began in 2006, when the Swiss Academy of Medical Sciences (SAMS) issued medical-ethical guidelines and recommendation for biobanks (Biobanks: obtainment, preservation and utilization of human biological material. SAMS medical ethical guidelines and recommendation; 2006, withdrawn in Nov. 2013). The SAMS guidelines stated that consent obtained from the donors of biological material “can generally also cover the further use of samples and data for future research projects”. If research requires the removal of human biological material, envisages research with non-anonymized samples or poses risks, donors must expressly give their consent to a research project. Based on these guidelines, in 2010, a working group – consisting of the Swiss Biobanking Platform (SBP), the SAMS, and the data protection commissioner of the cantons of Zurich and Basel-Stadt – published templates for GC (information and consent) and for biobank regulations (Salathé, Bulletin des médecins suisses 2010; 91:19-20).

An update on the implementation of the Swiss GC

Since February 2019, hospitals and research institutions in other networks have now the opportunity to use a harmonised GC for their projects. The national GC covers the further use of coded genetic and non-genetic data and/or biological samples for research according to the HRO (arts. 29, and 32). The scope applies only to data and samples collected during the hospital stay and may include data from research projects. It does not cover additional data/sample collection (HRO, chap. 2), such as additional examinations or drawing additional blood samples. The national GC applies the opt-in option, meaning that the patients or their representatives must actively say yes to the use of their data/samples. Without this active opt-in option, the data and samples must not be used. The opt-out option – meaning that if no objection is communicated by the patient, but that patient was informed, the use of coded, non-genetic data or the anonymisation of samples is permitted – is not accepted within the national GC, even though it is allowed according to the HRA.

For adults lacking the capacity of judgement, their legal representatives will receive the same information as the patient. They are allowed to decide and sign on behalf of the patient. The same is true for children. Finally, in the case of incidental findings, donors are informed that they may be contacted if the findings are pertinent for their health and if a clinical action is possible. Donors who do not want to be informed at all about the existence of incidental findings must refuse GC.

Table 2 summarises the current state of use of the GC at Swiss university hospitals (this listing is based on direct communication between the SCTO Regulatory Affairs Platform and the respective institutions, from December 2019 to January 2020). As of early 2020, two hospitals (Basel and Geneva) out of five are using the version 2 of the national GC, one (Bern) is also committed to implement it in 2020. Another hospital (Lausanne) is working on this version 2 to propose additional complements, as requested by their local ethics committee. A study is also planned in 2020 to test the different modalities of presentation of the GC to patients and to find out which model is preferred. The last hospital (Zurich) uses a local version of GC.

Overall, all the five university hospitals have had an established GC process in their institutions for a few years already, representing thousands of GC forms already signed by patients. As an example, at the University Hospital Geneva, the recruitment was launched on April 2017. Up to January 2020, around 40 000 patients signed the GC. Among them, 92% agree to the further use of their biological material and health-related personal data for research projects. These numbers prove the strong patients’ engagement for research. They also illustrate how hospitals are efficient for recruiting in- and out-patients.

Outlook

The adoption of a GC approach for the use of health-related data and samples represents an attempt to balance the needs of modern research to access large amount of data and samples with the matters of privacy and security. Despite divergent opinions on certain aspects, the implementation of a national harmonised GC that guarantees access to and sharing of a large pool of biomedical personal data in accordance with the HRA, represents a significant milestone for research in Switzerland.

However, for the use of big data, the GC model must evolve, while respecting ethical, legal, and societal imperatives, towards a new, more interactive, transparent, and dynamic model, rather focused on the general public and not only on the patients. New consent solutions are currently under development throughout Switzerland and the article “Developing innovative procedures for obtaining informed consent: three solutions underway” gives an overview on some of them.

The announced revision of the federal ordinances on human research planned for the end of 2020 might also address this subject and provide more clarity. New topics around GC should be addressed too, such as the implementation of data governance structure to help the exchange of data.

Further Reading

1. Kegley J (2004) Challenges to informed consent. EMBO reports 5(9):832-836Caulfield T and Murdoch B (2017) Genes, cells, and biobanks: Yes, there’s still a consent problem. PLOS Biology 15(7): e2002654
2. Mikkelsen RB et al. (2019) Brad consent for biobanks is best – provided it is also deep. BMC Medical Ethics 20:71
3. Martani A et al. (2019) Regulating the secondary use of data for research: arguments against genetic exceptionalism. Frontiers in Genetics 10:1254