Fra: NEM

Til: SHD, 20.3.02


Det vises til brev av 18.12.01 fra departementet med anmodning om at høringsuttalelsen utformes på engelsk. Utkast til protokoll ble behandlet på komiteens møte den 6. mars 2002. Det ble innsendt svar den 18.03.02. Dette brevet erstatter det forrige og er fullstendig.

Vi er bedt særlig om å kommentere artiklene 13 og 16 til departementet. Når det gjelder artikkel 13, er den uproblematisk da kravene allerede oppfylles av de regionale komiteene for medisinsk forskningsetikk. Det samme gjelder artikkel 16 (jf. veiledningen til søknadsskjema). Disse artiklene er derfor ikke omtalt i det følgende svar.

Vi vil særlig anbefale departementet om å gjøre våre retningslinjer for inklusjon av kvinner i medisinsk forskning kjent for Europarådets styringskomite for bioetikk i den videre bearbeidelse av protokollen. Retningslinjene er tilgjengelige på engelsk på vår hjemmeside.

Protokollen reiser spørsmål om nødvendigheten av å lovhjemle komitesystemet og eller etablere lover for å gi ekstra beskyttelse for sårbare forsøkspersoner. I rapporten om etisk prøvning i Sverige som nå er utarbeidet av det svenske utdanningsdepartmentet har man trukket konsekvensene av dette i form av et forslag om å lage en ny lov om etisk prøvning. Dette vil i så tilfelle få store konsekvenser for det norske systemet og grunnlaget for dens virksomhet. Komiteen har derfor i sitt møte den 6. mars 2002 besluttet at den vil anmode Utdannings- og forskningsdepartementet om å utrede spørsmålet om lovhjemling.

The committee supports fully the aims of the protocol to propose measures to safeguard human dignity and the fundamental rights and freedoms of the individual with regard to biomedical research.

In general the Norwegian committee system for ethical review is already functioning in accordance with the protocol.

Too strict requirements

Regarding some of the articles we are of the opinion that the requirements are too strict or too limited.

Art. 5 states that "Research is only justified if it has the potential to generate scientific understanding that may be a basis for improvements in human health". We consider it important that the article does not prevent qualitative research (e.g. semi-structured interviews with seriously ill patients). Qualitative research may have little or no potential for "improvements" in human health. We concede that the interpretation of the article to some extent depends on the understanding of "health". In our opinion, it should be made clear that "health" in the context of art. 5 must be interpreted as not only physical, but also mental health and wellbeing in general.

Concerning art. 8 we raise the same objection as to article 5. In addition we will not advice limiting exceptions to two conditions only. The exceptions, as they stand, are open for wide interpretations (e.g. one can never exclude the possibility that research has "the aim of contributing" to the given goals). In our view it is preferable to state that exceptions must be accepted by the ethics committee.

Lack of gender specific research

The protocol lacks sufficient sensitivity to the issue of inclusion of women in all research, e.g. in article 13 vii, article 23.

We recommend that a new article is inserted in the protocol on this point.

On the basis of the work done by NIH on inclusion of women and minorities in medical research (1994), our committee published Guidelines for the inclusion of women in medical research. Gender as a variable in all medical research (2000). The guidelines pay particular emphasis on the inclusion of women of fertile age and pregnant women, and the need for gender-specific analyses. In Norway researchers are now required to address the question of gender.

Withdrawal and voluntariness

Under article 16 iv) it is stated that a person can withdraw consent at any time. To strengthen the voluntary aspect of participation, we will recommend an addition saying that a person can withdraw at any time without stating reasons or giving explanations. In our experience many investigators (and sponsors) add conditions for withdrawal (explanation, last meeting, check-up, etc).

Protections of persons not able to consent

The committee supports the conditions of the protocol for doing research with persons not able to consent. It also supports that non-therapeutic research should be permitted under strict conditions.

It is, however, difficult to fulfil the requirement that these exceptions must be prescribed by law. Neither the committee system nor the conditions (stated in the terms of reference given by th Ministry of Education and Research) are enacted as Norwegian law. We recommend that the protocol accepts that conditions may be prescribed in a variety of ways according to national traditions. We are not convinced that formal law gives better protection than our own guidelines and committee system.

Research during pregnancy and breast feeding

Article 23 states conditions for interventions for research during pregnancy etc. The committee considers these conditions too strict. The committee approved the following guidelines for accepting research with pregnant women. A significant difference is that our guidelines encourage this research (within given conditions) while the protocol makes this type of research an exception. We note that the article allows for proportionate risk. This is supported in our guidelines. We suggest that the Council of Europe considers our guidelines on this issue:

III Inclusion of pregnant women

  1. Pregnant women shall always be included in studies relating to pregnancy and should be included in other types of medical research that are relevant to the situation of pregnant women.
  2. The interests of the pregnant woman and her foetus shall always take priority over research considerations. Studies must be discontinued immediately where the interests of the woman or the foetus dictate the appropriateness of following other procedures than those indicated by the study protocol.
  3. In the case of drugs for use by women of fertile age, separate studies should be carried out on pregnant women, at least on severe conditions requiring treatment during pregnancy, ensuring that the knowledge necessary for such treatment is obtained. Diabetes, asthma, epilepsy, mental illnesses are examples of such severe conditions.
  4. The following conditions apply to the inclusion of pregnant women:

a) Studies of pregnant women shall offer potential therapeutic benefit to women or foetuses.

b) If molecular structure, animal experiment studies or similar indicate that a drug might be teratogenic, pregnant women shall as a rule not be included in trials. Inclusion may, however, be considered despite preclinical/pharmacological/clinical indications of possible teratogenicity if the benefit is deemed to be greater than the risk for the woman and/or the foetus.

c) When pregnant women are included in a study, the project leader has a duty to take all steps possible to exclude the risk of foetal damage. This duty means that the project leader must have knowledge of relevant documentation from research and clinical practice and of potential foetal damage associated with use of the method or treatment in question. Adequate preclinical and/or clinical documentation on non-pregnant women and adequate clinical experience of other patient groups are prerequisites for conducting studies on pregnant women.

The Norwegian Medicines Agency shall determine whether the documentation and clinical experience are adequate for each individual study.

d) Any drug studied should have marketing authorisation in Norway and/or an EEA member state before the inclusion of pregnant women.

e) All intervention studies are subject to a follow-up requirement. The woman shall be followed up during pregnancy and the child shall be followed up after birth.

f) The decision to participate in the study may only be taken by the woman herself.

Exceptions from giving information

Article 10 in the Convention states that everyone is entitled to know any information collected about his or her health. Section 3 gives the possibility for exceptions "in the interests of the patients". The committee is of the opinion that there are situations in which information is inadvicable (e.g. in some types of genetic research). It seems also reasonable that research subjects should be protected against possible misuse by third parties that may have interests in the information (e.g. insurance companies, authorities regarding e.g. paternity). The question of exceptions from giving information ought to be treated explicitly in the protocol (e.g. under chapter VIII, as well as article 16, section vii).

Temporary negative impact

In article 20 the protocol states that it will tolerate research interventions that result in "very slight and temporary negative impact on the health of the person concerned." The committee supports fully the explicit mention of permitting negative impact on health when it is slight and temporary, since it has been insecurity among committees reviewing protocols whether this should be permitted or not.


Under article 30 on the chapter on safety and supervision it is suggested that adverse events and negative developments should lead to evaluation and information to participants. In this we agree fully. The protocol avoids, however, to deal with another difficult question: what shall be done when the developments are positive and the research can document positive effects for partipants. It seems to us that this situation also needs re-examination, and possibly also a procedure to examine when it is no longer ethically acceptable to continue the research without offering the participants access to effective treatment. We think this is of great importance since we have had examples of sponsors and researchers that refuse to stop ongoing research, even when they admit that the trial medication is effective.

Non-interference with necessary clinical interventions

In article 30 the protocol states an important ethical issue, namely to assure participants in research access to proven methods etc without delay. The committee fully supports this. We also support the exception clause given in the third paragraph allowing the use of placebo "where withholding of active treatment does not present unaccepatble risk or burden." We note that this exception is not in accordance with a literal interpretation of the Declaration of Helsinki (nr. 29).

Questions of prescriptions by law

The protocol is a legal instrument presupposing that some of the conditions for research ethics must be established by national law (e.g. article 18.2, jf. explanatory report, nr. 42). As far as we can see it is an open question whether the independent committee system as such must be established by law. In article 9 it seems that the protocol presupposes that "the competent body" is based in law in order to have the authority to approve research projects. On this account, the committee will take initiative to ask the Ministry of Education and Research in Norway to deliberate the issue of vesting the committee system with legal authority.