Our opinion on ...
- Executive Summary
- Necessity for a response
- Clinical trials
- General principles
- Other considerations
The present paper constitutes the input of Alzheimer Europe and its member organisations to the ongoing discussions about the Clinical Trials Directive of the European Union.
It does not constitute a general position on the participation of people with dementia in other kinds of research, even if some of the following comments would be equally valid for such a position paper. A position paper on the participation of people with dementia in other kinds of research will be published shortly.
Alzheimer Europe would like to recall some general principles which guide this present response:
- A diagnosis of dementia does not in itself constitute a lack of legal capacity.
- An early and accurate diagnosis of dementia is essential and people with dementia have a right to be informed about their diagnosis.
- People with dementia should be encouraged to write advance directives regarding important decisions in case they become incapacitated.
- National governments should put into place legislation recognising the legally binding character of advance directives.
- Informed written consent has to be given by the person with dementia or his/her legal representative for important treatment decisions.
On the basis of these principles, Alzheimer Europe has developed the following position with regard to the participation of people with dementia in clinical trials:
- In the early stages of their disease, people with dementia can themselves consent to clinical trials or declare their willingness to participate in clinical trials in an advance directive.
- Legal representatives should be able to consent on behalf of people with dementia to participate in clinical trials, if the following main conditions are met:
- the potential direct benefit for the person’s health is clearly greater than the possible risks;
- the risk of causing discomfort or distress is minimal;
- the research has been approved by an independent ethics committee;
- the same results could not be obtained with other subjects.
Alzheimer Europe requests further information on the participation of people with dementia in Phase I drug trials and the use of the concept of "direct benefit" in placebo trials and wants to encourage an ongoing dialogue between political decision makers, patients' and carers' organisations, the pharmaceutical industry and researchers on this subject.
Based on its current information, Alzheimer Europe does not endorse the participation of people with dementia in clinical trials WITHOUT a potential direct benefit for the participants. Nevertheless it reserves the right to re-consider its current position after receiving further information from the scientific community and the pharmaceutical industry with regard to the kinds of research that would be covered by this definition.
Clinical trials are extremely important if the treatment of people with dementia is to be improved, as well as for the development of preventative measures and ultimately a cure. The participation of people with dementia in clinical trials is therefore necessary, yet it is equally clear that our approach to this question has to be dictated by the respect for fundamental human rights, such as the right to self determination, the freedom of the individual and the integrity of the human body.
Alzheimer Europe has looked at this question in the framework of two successive projects, the first consisting of an inventory of legislation affecting people with dementia in all the Member States of the European Union and the second which involved the drafting of recommendations on how to improve the legal protection and rights of people with incapacity due to dementia.
The present discussion paper outlines some of the recommendations of Alzheimer Europe and its member organisations and raises some points, which deserve further clarification and discussion.
The necessity for a response by Alzheimer Europe
Over the past years, the issue of the participation of people with dementia in research has become an increasingly debated topic. Some European countries have already developed legal instruments defining the conditions under which people with dementia may participate in research.
These legal provisions differ from one country to another, yet some attempts have been made on a European level to harmonize these rules, most importantly the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine of the Council of Europe and the Directive on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use.
In order for the voice of people with dementia and their carers to be represented in the ongoing discussions, Alzheimer Europe has developed the present Position Paper.
Participation in clinical trials
Alzheimer Europe would like to draw a distinction between various situations that might arise when people with dementia are asked to participate in clinical trials. Thus, it is important to differentiate, whether people with dementia
- are able to give informed consent
- are unable to give consent, but have expressed their wishes in an advance directive
- are unable to give consent and have not previously expressed their wishes.
As previously mentioned, a diagnosis of dementia does not imply an automatic loss of the person’s capacity to take important decisions, such as taking part in clinical trials.
A great number of people with dementia in the early stages of the disease will be able to fully understand the implications of taking part in clinical trials and should therefore be able to give their informed consent.
Nevertheless, since the loss of capacity is gradual, it might be appropriate in certain circumstances for the treating doctor to be consulted before the clinical trial can go ahead.
People with dementia may have expressed their wishes in an advance directive before the onset or in the early stages of their disease. Participation in clinical trials may be an issue that was expressly included in such an advance directive.
In such cases, wishes expressed in an advance directive can be considered as consent to participation in clinical trials. All restrictions or limitations, as to the fields of research that the person is willing to participate in, shall be fully respected.
Absence of consent or advance directives
This question has been discussed controversially by the member organisations of Alzheimer Europe and while a consensus could be reached on certain points, further clarification is needed before the organisation is willing to commit itself fully.
The following principles found unanimous agreement from all member organisations in order for a legal representative to give his/her consent to a person’s participation in clinical trials:
- the potential direct benefit for the person's health is clearly greater than the possible risks;
- the risk of causing discomfort or distress is minimal;
- the research has been approved by an independent ethics committee;
- the same results could not be obtained with other subjects,
- the legal representative has been specifically authorised to give consent by a court or by the person with dementia him/herself;
- the interests and the wellbeing of the adult with incapacity are always placed ahead of the interests of science and society;
- the necessary safeguards have been taken to protect the adult's privacy and to respect his/her dignity.
The above considerations closely mirror the preoccupations expressed in the amendments of the Committee on the Environment, Public Health and Consumer Policy of the European Parliament.
Nevertheless, some member organisations of Alzheimer Europe expressed their unease about the concept of "direct benefit" with regard to the conduct of clinical trials. Since most clinical trials include people receiving a placebo, these organisations feared that these trials could be questioned since no lasting "direct benefit" can be expected for the people receiving placebo. This issue deserves further clarification, as the position of Alzheimer Europe regarding "direct benefit" for research participants should in no way be construed as being opposed to the safe conduct of clinical trials.
Some scientists also say that the obligation of "direct benefit" would put into question the inclusion of people with dementia in Phase I drug trials where the safety of a medicinal product should be analysed. According to our information, Phase I trials do not, as a rule, involve people with the condition for which the product has been developed, but rather healthy individuals, since the aim of the study is not to show the efficacy, but only the safety of a given product.
On the question of whether people with dementia should be able to participate in clinical trials without potential direct benefit for them and without them having explicitly consented to the research, no consensus position could be reached between the member organisations of Alzheimer Europe. Most organisations reserved their judgement on this issue, unaware of the kind of clinical trials that may be covered by this definition.
We would therefore be grateful to be informed by the scientific community and the pharmaceutical industry about which clinical trials might be jeopardised by the current position of Alzheimer Europe limiting its approval to clinical trials with a "direct benefit" for participants.
Alzheimer Europe and its member organisation would welcome the organisation of a true dialogue on this subject between the interested parties; i.e. political decision makers, patients' and carers' organisations, the pharmaceutical industry and researchers in the field.
At its Annual General Meeting in Munich on 15 October 2000, Alzheimer Europe adopted recommendations on how to improve the legal rights and protection of adults with incapacity due to dementia. These recommendations obviously need to guide any response of the organisation regarding the participation of people with dementia in clinical trials.
Alzheimer’s disease and other forms of dementia are progressive disorders, which may result in a gradual deterioration of a person’s ability to function and a subsequent loss of a person’s capacity to communicate or make important decisions regarding his/her life.
Yet, a diagnosis of dementia does not in itself constitute a loss of the capacity to take such decisions. Thus, the earlier a diagnosis of dementia can be made, the longer a person will be able to participate fully in decisions affecting his/her life.
Equally, in order to safeguard people’s rights to self determination, it is essential to guarantee that every person diagnosed with dementia has a right to be informed of the diagnosis.
Furthermore, Alzheimer Europe would like to encourage newly diagnosed people with dementia to consider drafting advance directives in which they set out their future wishes regarding the conduct of their lives in case they become incapacitated and hence no longer able to take such decisions.
Alzheimer Europe campaigns for these advance directives to be legally binding and calls upon national governments to put into place the necessary legislation.
Informed written consent should be sought for important treatment decisions. In case, the person concerned is no longer able to give such consent, a legal representative should be able to do so on his/her behalf, provided that he/she has taken into account the previously expressed wishes of the person.
At any time during the clinical trial, the person with dementia or his/her legal representative shall be able to withdraw their consent. Also, any non-verbal indications by the person of his/her unwillingness or discomfort to continue the clinical trial, shall be justifiable reasons to discontinue the research.
Alzheimer Europe strongly supports the amendment of the Committee on the Environment, Public Health and Consumer Policy to ensure that patients or patients’ representatives are included in or, at the very least, fully consulted by ethics committees in charge of endorsing the research protocol.
In case of conflict of interest, when the treating doctor and the doctor in charge of the clinical trial are identical, a second opinion by a doctor not implicated in the research will be necessary.
Last Updated: Thursday 06 August 2009