Fra: The National Committee for Medical Research Ethics and The Regional Committees of Medical Research Ethics in Norway

Til: CIOMS, 22.6.01


The draft guidelines were discussed by the National Committee for Medical Research Ethics and with the leaders of the Regional Committees of Medical Research Ethics.

The committees are of the opinion that the draft guidelines are thorough, readable and reflective of common standards of research ethics today. We think it is very valuable that the draft is explicit about how to handle research in developing countries.

We noticed that the specific guidelines from 1993 related to epidemiological research (guideline 9) is deleted in the revision. We think it is unfortunate, because consent to participation in epidemiological research needs particular guidelines, especially when projects are running for long periods of time, and when there is need for new analysis of data and biological material collected years ago. We think it is important that guidelines allow for general (broad) consent and passive consent.

The draft uses the phrase of "inviting research subjects to serve" in several of the guidelines. In the committees in Norway we rarely accept "invitations" to research. Invitation will often be understood as a spoken or written request for someone to take part. Invitation also seems to entail some kind of familiarity which encourages and or induces participation. These implication of invitations may undercut the emphasis on voluntariness. We will therefore recommend that the guidelines use a more neutral word.

Comments to specific guidelines:

Guideline 1

We suggest that "adequate" is replaced with "thorough" as it is stated in guideline 3: "proposed studies…are based on thorough knowledge of the pertinent scientific literature".

Guideline 3

Commentary Scientific review, 2. par.:

We agree with your view. You could list a third reason: a local (regional or institutional) committee may be composed of members that have too close ties personally or professionally to the researchers whose research they are to evaluate independently.

Commentary Risks and benefits, 3. par.:

We’d like to point out that genuine non-altrusitic reasons and interests can also be acceptable for participating in research.

Commentary Committee membership, 1. par.:

We strongly endorse the presumption for including lay persons.

We will warn strongly against the recommendation to include representatives of specific groups or advocates of such groups as members of the committee. Rotation and handling of conflict of interests will not resolve this problem. The groups could – and sometimes should – be heard by the committee, but they should not be represented in the committee.

Commentary Sanctions, 3. par.:

The comment that "editors should consider refusal to publish the results of research conducted unethically" is too weak. We suggest that the guidelines recommend editors to refuse to publish unethical research. To consider the deprive of (poosible) benefit (for society) implies the danger of legitimizing unethical research.

Guideline 4

Generally the concept "therapeutic" is unclear and lacks a definition or explanation. This seems necessary to be able to distinguish between "benefit for the individual" and "benefits to society". Even projects that do not have any "direct therapeutic benefit" for the individual can be beneficial to the individual in other ways (meaningful, e.g.).

Commentary Randomized controlled trials, 1. par.:

The sentence beginning with the primary justification for a randomized trial states a very important requirement with which we agree. The requirement is stated in a very clear and appropriate way.

Guideline 5:

What is exactly meant by temporary inability to consent. The commentary needs to define and explain what is meant by temporary.

Guideline 6:

Our compliments. The guideline is appropriate and needed. We strongly support the last sentence in the Commentary, par 2 on exploitation.

Guideline 7:

We support that there should be acceptable "departures" from the requirements set by the Declaration of Helsinki, as stated in the Commentary.

Commentary, par. 6:

We are worried that the sentence referring to "a locally available product" as an acceptable comparator sets a lower standard for research in developing countries with the possibility for exploitation, especially when research is sponsored by large pharmaceutical companies. The three proposed conditions do not seem sufficient to prevent exploitation. E.g. what does it mean to make a product "reasonably available" in the host country?

As this paragraph stands it should be deleted. If CIOMS thinks it is necessary to find pragmatic resolutions in regard to "locally available products", we are of the opinion that the conditions must be stricter and clearer.

Guideline 8:

Commentary, par. 2:

We’d like you to pay attention to the sentence in which informed consent is described as an "imperfect safeguard" for the individual. The wording seems unnecessarily paternalistic implying that competent research subjects do not know their own best interest. However, if you intend to stress the importance of the responsibility of the investigator (regardless of consent) and the independent safeguard of the committee, we think this should be stated positively.

It seems to us that the commentary rather should concentrate on the imperfect safeguard of using "properly authorized representatives" to give proxy consent. Here we think it is very appropriate to discuss the limitations of an imperfect safeguard.

Guideline 9:

We support the inclusion of nr. 13. In nr. 17 it is not clear what "such injury" refers to.

Commentary, Risks:

Our compliments. The commentary contains important qualifications.

Commentary, Use of biological material:

We support the acceptability of passive consent in many of these cases.

Guideline 10:

We strongly support the inclusion on the guideline of renewal of informed consent.

Commentary, Documentation of consent

It seems to us that some "indications" of consent should not be acceptable, e.g. when a researcher has the impression that a certain subject would have consented. The word "imply" opens up for too many flexible "indications" and constructions of consent. We will advice that you distinguish clearly between acceptable indications and non-acceptable indications.

Regarding the issue of community consent and your reference to "formal consultation"

we think the issue is more complicated. What criteria defines a "community", what is "formal consultation" and how is "substantial support" assessed? It also seems that it is too strict to invest a "gate keeper" (formal representative body of a community) with authority to veto research on behalf of a community. The requirement will be even more difficult to handle if the criterion is "substantial support in the community". At the same time

any benefit of a research project must be reviewed against possible risks of discrimination or stigmatization of a community.

Guideline 14:

We agree with most of the proposed conditions for research involving children.

We mean, however, that children over 16, and sometimes over 12, can give valid consent without the permission of parents. We will suggest that the commentary will allow for this under specific conditions.

Guideline 15:

The requirement of proxy consent for subjects lacking capacity to consent is not allowed in our jurisdiction.

The decision to include research subjects without capacity must be taken by the researcher after approval by the committee. If possible, relatives ought to be informed, and if they object, their wishes should be respected.

For the group who lacks capacity (have reduced competence) we are strongly against requiring proxy consent. The requirement removes the autonomy of these research subjects on an unnecessary basis, in addition to the insecure foundation of proxy consent as an imperfect safeguard (see above).

Commentary, Anticipation of consent:

Anticipation of consent is a difficult matter generally, and more so in the case of persons with reduced competence. Discussions about advanced directives point to these difficulties regarding e.g. the prediction of hypothetical and vague future conditions and the possibility of changing values with changing circumstances. In our view a proxy will not help the matter, to the contrary the problems will be greater.

We will therefore ask that the commentary on anticipation of consent be deleted.

Guideline 17:

We strongly support the inclusion of this guideline.

Commentary, 1. par.:

The analogy of the second "research participant" to infants and young children is not very helpful when the legal status of fetuses differ substantially internationally. The claim that there is "no difference, in principle" requires explanation and justification.

We think the commentary could – and should - be written without the analogy and without implying ontological presuppositions.

Commentary, 2. par.:

To avoid squibble about "fetal abnormality" and criteria for what is meant by abnormality, the last sentence could state plainly that pregnant women should not be recruited for research in jurisdictictions where abortion is not legal.

Guideline 18:

The guideline should be deleted. It is not desirable to have a guideline on a very narrow and specific area in which there is substantial disagreement ethically, legally and culturally.

Guideline 19:

Commentary, Confidentiality between researcher and subject, par. 4:

The exception clause in the sentence of non-disclosure to relatives need to be explained. It is not clear why disclosure is "unavoidable". Disclosure is a very serious matter that can affect people’s lives in profound ways. If exceptions are to be tolerated, they should be clearly stated. We would prefer the except-clause to be deleted. Exceptions should be left to the discretion of committees to review in each particular case and circumstance.