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Consent in psychiatric biobanks for pharmacogenetic research

Frederieke H. van der Baan, Rose D. C. Bernabe, Annelien L. Bredenoord, Jochem G. Gregoor, Gerben Meynen, Mirjam J. Knol, Ghislaine J. M. W. van Thiel
DOI: http://dx.doi.org/10.1017/S146114571200048X 677-682 First published online: 1 April 2013


In psychiatric practice, pharmacogenetics has the potential to identify patients with an increased risk of unsatisfactory drug responses. Genotype-guided treatment adjustments may increase benefits and reduce harm in these patients; however, pharmacogenetic testing is not (yet) common practice and more pharmacogenetic research in psychiatric patients is warranted. An important precondition for this type of research is the establishment of biobanks. In this paper, we argue that, for the storage of samples in psychiatric biobanks, waiving of consent is not ethically justifiable since the risks cannot be considered minimal and the argument of impracticability does not apply. An opt-out consent procedure is also not justifiable, since it presumes competence while the decisional competence of psychiatric patients needs to be carefully evaluated. We state that an enhanced opt-in consent procedure is ethically necessary, i.e. a procedure that supports the patients’ decision-making at the time when the patient is most competent. Nevertheless, such a procedure is not the traditional exhaustive informed consent procedure, since this is not feasible in the case of biobanking.

Key words
  • Biobank
  • consent
  • ethics
  • pharmacogenetics/pharmacogenomics
  • psychiatric in-patients


A 40-year-old woman, exhibiting psychotic symptoms, with no previous history of psychiatric illness, is acutely admitted to a psychiatric clinic. As part of routine care, blood is drawn to assess her somatic condition. Antipsychotic treatment, which is started immediately, consists of 2 mg haloperidol daily. The patient's blood sample is used to predict her drug metabolizing capacity by genotyping cytochrome P450 2D6. This enzyme is involved in the metabolism of many antipsychotics. The pharmacogenetic test results show that this patient has an increased metabolic activity and is therefore at risk for low serum levels and decreased activity of haloperidol when given the standard dose. However, guidelines on dose adjustment are currently lacking for this genotype (Swen et al. 2011).

In psychiatric practice, predicting a patient's response to a specific drug is difficult, which complicates finding the optimal drug and dose for a patient. Pharmacogenetic testing is not (yet) common practice in psychiatry and more pharmacogenetic research in psychiatric patients is warranted to determine the clinical implications of genotype-guided treatment (Kirchheiner et al. 2010). In our case, the patient's blood was collected for clinical purposes. Future (pharmacogenetic) research could be facilitated by storage and use of blood samples. This raises the question of whether, and under what conditions, researchers are allowed to store and use such samples for research. Is consent required? The issue of consent is particularly a challenge here since the samples are not collected in a trial setting where informed consent is standard for participants. Also, if consent is required, is use of the sample allowed if the patient is not competent at the moment of blood withdrawal?

This paper identifies and explores what type of consent is appropriate in psychiatric biobanks that are built and maintained primarily for pharmacogenetic research purposes and the consequences for patients and psychiatric health professionals. Specifically, this paper focuses on psychiatric patients admitted in the acute ward. This patient population is not as extensively studied as the others, which results in little evidence on (personalized) treatment. Blood withdrawal is part of routine care of these patients and, at least in some psychiatric hospitals in the Netherlands, pharmacogenetic testing is already routinely done, as illustrated in the case. We hope to contribute to the future organization of psychiatric hospitals, in which samples are stored and research is enabled in an ethically justifiable way.


The overall rationale of biobanks is to house and facilitate ongoing research on human biological material (Sheehan, 2011). They vary according to the type and number of tissues stored, the extent of genetic, clinical and personal data and the permitted use of the samples and data. In large databases such as the UK Biobank, samples are usually specifically collected for research aims. In smaller hospital-based, disease-specific (or clinical) biobanks, samples are collected and stored for diagnosis and treatment, but any residual material can also be used for research. The introductory case is an example of such a biobank.

Biobank research has several special characteristics: samples are usually stored for a long time and biological samples can be matched with phenotypic data. The exact research questions for which the samples will be used are not formulated at the time of sample collection. This implies that being a donor for a biobank can have a greater impact than a donor may foresee. That underscores the importance of considering the appropriate type of consent, even more for the enrolment of potentially vulnerable groups. There has been debate on who should be considered ‘vulnerable’ in research and for what reason (Levine et al. 2004). Nonetheless, the potential diminished capacity to consent and the context of being institutionalized are generally considered as inferring a need for special protection in medical research.

In the case of the 40-year-old woman, both factors apply.


Whereas consent is a standard ethical and legal requirement for clinical research, the appropriate type of consent for residual tissue and biobanking research is less consensual. Positions defended in the literature range from informed consent to a one-time general (or broad) consent to opt-out procedures to no consent at all (Emanuel & Menikoff, 2011; Helgesson et al. 2007; Hofmann, 2008; Sheehan, 2011; Stjernschantz et al. 2011; Wendler, 2006). In addition, neither the type of consent nor the appropriate type of ethics review is a settled issue. After all, the debate on whether such types of research need approval of a research ethics committee (institutional review board) has recently been re-opened by a proposal by Emanuel & Menikoff (2011) to exempt minimal risk research from ethics review. However, whether biobank research should automatically be allocated to the category of ‘minimal risk research’ remains to be seen.

Table 1 gives an overview of the different forms of consent. In exceptional circumstances, consent is waivable (CIOMS, 2008; US Department of Health & Human Services, 1991). In addition to a substantive justification, two conditions are – according to international guidelines for storing human biological samples for future epidemiological research – necessary for waived consent: the risks to participants should be no more than minimal and obtaining consent would make the conduct of the research impracticable (Bernabe et al. 2011; CIOMS, 2008). Do these conditions apply to the woman in the case or to any in-patient in a psychiatric ward whose blood sample and DNA information are stored in a biobank with a pharmacogenetic research aim?

View this table:
Table 1

Overview of different forms of consent with the consequences for donor and research

Forms of consentInformation to donorConsequences for research
Waived consentDonor is not made aware that tissue may be used for research.Substantive justification is necessary; subsequently, the sample can be used for research.
ConsentOpt-outThrough the use of various media for information dissemination, it is presumed that donor is aware that tissue may be used for research. If he/she does not explicitly decline consent, consent is granted. Competency of potential donors is presumed.As long as consent is not explicitly declined, the sample can be used for research.
Opt-in (informed consent)BroadDonor is actively informed that tissue may be used for research, although exact research questions are not specified.If consent to unspecified use of the sample is given (consent to governance), the sample can be used for research.
He/she has the option to agree or disagree with the collection and use of the tissue.When new research questions arise, the sample may be re-used without renewed consent, as long as it falls within the scope of the broad consent.
SpecificDonor is actively informed that tissue may be used for research and about the exact nature of the research and the research questions.If consent for a specific research is given, the sample can be used for this specific research question.
He/she has the option to agree or disagree with the collection and use of the tissue.When new research questions arise, the donor must be approached to re-ask consent.

Minimal risk

Risk is considered as minimal when the probability and magnitude of harm or discomfort anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological tests (Committee on Human Studies, 2011). Some have argued that the risks of biobank research are low or even non-existent (e.g. Petrini, 2010), which indeed seems the case if researchers only have access to coded data and no individual results will be communicated to the patients or third parties. However, even in coded data, although the probability is small, the risk of revealing information must be considered since magnitude wise, as will be shown shortly, the risks could be noteworthy.

Even if physical risks may be negligible or even non-existent, this is not necessarily the case for other risks posed by a biobank, such as social, psychological and economical risks. The risks of biobanking research are largely informational, as they could encompass harm that results from the inappropriate release and distribution of information and not from the research intervention itself (Emanuel & Menikoff, 2011). The information stemming from (pharmaco-) genetic research may have beneficial consequences, but it can also cause distress and anxiety, affect someone's opportunity to maintain insurance or be stigmatizing (Bredenoord et al. 2011; Haga & Burke, 2008; Netzer & Biller-Andorno, 2004). The amount and nature of information about a person is potentially limitless, which, if inappropriately disclosed, may affect the rights and well-being of the person in question, as well as his/her family's (Bredenoord et al. 2011). As more people get to have access to such data from the psychiatric biobank, the risk of breaches in confidentiality also increases.

Such risk is not comparable to daily life risk nor to the risk of a routine (psychiatric) test. We do concede that risks may possibly be diminished to no more than minimal, given consensual safeguards within the biobanking system. This sets high demands on adequate systems of data security, feedback policy and risk management and clear guidelines regarding the use of tissues and data. It also requires awareness of biobank researchers regarding the governance policies and, obviously, their compliance to these. The current status, particularly where infrastructures are built that makes it possible to link and network biobanks around the world in unprecedented ways (Kaye, 2011), and the potential significance of genetic research results does not allow us to claim that the risks are minimal in nature.


In general, impracticability could be an issue if, for example, locating patients whose records will be used for research is difficult. For patients such as in our case, who are accessible at the moment of blood withdrawal, there is no obstacle to ask for consent for biobanking the sample – except when the patient is incompetent (see below).

Both conditions under which waiving of consent might be justified are not applicable in our case, thus waiving of consent is unethical here.

Vulnerability and competence of psychiatric patients

Psychiatric patients admitted in the acute ward are considered to be ‘cognitively vulnerable’, although their degree of vulnerability varies over time (Bielby, 2008). Their vulnerability partly depends on their decisional competence, i.e. the patient's capacity to decide given a specific situation (Beauchamp & Childress, 2008) and, in our case, it is the capacity to decide to consent (or not) to biobank research.

It has been demonstrated that ‘mental incapacity to make decisions on treatment is common in people admitted to psychiatric wards’ (Owen et al. 2008). Although most studies deal with the capacity of psychiatric patients regarding treatment decisions, it seems reasonable that these findings are also applicable to decisional competence required for biobanking and research. The decisional competence of psychiatric patients fluctuates; patients are likely to regain competence when the acute phase of disease has passed and competency could again be jeopardized when symptoms recur. For some of these patients, supporting measures in a decision-making process are effective (Dunn et al. 2001), so that otherwise incompetent psychiatric patients achieve sufficient decision-making capacity to consent. Other patients permanently lack decisional capacity, in which case a legal representative is necessary.

Type of consent

There are two possibilities for obtaining consent: an opt-in system and an opt-out system. The former entails explaining and making a patient sign an informed consent form; the latter involves making a patient know, either verbally or through a leaflet, about biobanking and about the opportunity to refuse it (CIOMS, 2008). Considering that an opt-out procedure is usually administratively easier, does it sufficiently protect the patient's rights and interests in our case?

The foregoing discussion points to the need to carefully evaluate the decisional competence of the patient to consent to biobanking and research. This requirement is contrary to the essence of an opt-out procedure, in which competency is presumed. Par ticipants are assumed to have the competence to understand the research and to opt out, without confirming whether or not these capacities are indeed within the participants’ competence. Moreover, although a positive normative judgement about the biobank research enterprise is probably rightly positioned as the default position, this can at the same time be subtly coercive for people who wish to deviate. Hence, an opt-out procedure is not ethically defensible in our specific case. Moreover, the assessment of competency approximates the very demands of an opt-in procedure, save for the final signing of the informed consent form. An enhanced opt-in procedure that supports the patients’ decision-making and promotes asking consent at the time when the patient is most competent is what is ethically necessary. The extra guidance can be in the form of technological aids, such as a videotape or PowerPoint presentation explaining the research procedures, although the human element seems pivotal (Bielby, 2008). To illustrate, Lapid et al. (2004) showed that a 30-min session with a psychiatrist discussing frequently raised concerns about a procedure increased understanding, reasoning and choice in elderly depressed persons. When a patient, despite the extra support, does not achieve sufficient decisional capacity during the admission, a legal representative should be allowed to give proxy consent. This type of consent will have administrative and procedural repercussions. Psychiatric health facilities that also biobank their patients’ samples need to ensure that a supported informed consent procedure is in place. This means not only that forms and various media are available, but also that the health practitioners are briefed and trained to administer such a supportive informed consent process.

It is necessary to note that our endorsement of an opt-in procedure does not imply a traditional exhaustive informed consent procedure. Given the nature of biobanks, such a procedure is plainly not feasible because the traditional informational requirements (Beauchamp & Childress, 2008; World Medical Association, 2008) of an informed consent procedure are not available at the time of biobanking. There have been discussions about broad informed consent, which is consent on the unspecified use of samples for any type of biomedical study. We think that informed consent in psychiatric biobanks ought to be included within these discussions. An opt-in system, specifically for biobanking psychiatric patients’ samples, should be developed to meet the ethical requirements of good research.


In psychiatric biobanks where biomaterials with explicit DNA information are stored for pharmacogenetic research purposes, waiving of consent is not ethically justifiable since the risks of such biobanks cannot be considered minimal and the argument of impracticability does not apply. Neither is an opt-out consent procedure justifiable since it presumes competence and the decisional competence of a cognitively vulnerable group of psychiatric patients needs to be carefully evaluated. Only a supported opt-in procedure is justifiable in this case, that is, a procedure that considers the individual patient's condition and the time when the patient is most competent. As such, psychiatric health facilities that biobank need to ensure that they and their personnel are administratively and procedurally prepared for such consent.

Statement of Interest

The PhD projects of R. D. C. Bernabe and F. H. van der Baan are funded by the Dutch Top Institute Pharma.


This study was performed in the context of the Escher project (T6-202), a project of the Dutch Top Institute Pharma, Leiden, The Netherlands. The authors are entirely responsible for the scientific content of the paper, no assistance was received in preparing this manuscripts for publication.


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