Proposition 51K0798

Projet de loi relatif aux expérimentations sur la personne humaine.

General information ¶

Submitted by

PS | SP MR Open Vld Vooruit Purple Ⅰ

Submission date

Feb. 10, 2004

Official page

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Status

Adopted

Requirement

Simple

Subjects

EC Directive bio-ethics experiment on humans

Voting ¶

Voted to adopt

Vooruit Ecolo LE PS | SP Open Vld MR

Abstained from voting

CD&V N-VA FN VB

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Discussion ¶

March 25, 2004 | Plenary session (Chamber of representatives)

Full source

Mr. Speaker, Mr. Minister, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker, Mr. Speaker. Demotte, relating to experiments on the human person. The report will be made by me, for the general discussion, and by Mr. Goutry, for the amendments.

First of all, I would like to highlight the positive climate that has reigned throughout the duration of the work. This bill, after amendments, was adopted in the committee by 12 votes and 2 abstentions. However, many parliamentarians regretted the short time we were given to transpose the European Directive 2001/20 into Belgian legislation. This transcription is three years old. Even the State Council complained that it did not have enough time to examine this subject in depth. Eventually, auditions could have been organised.

The concern of this bill is to provide a legal framework because our country is in a paradoxical situation. The Belgian law states that the intervention of the doctor is only legitimate for a preventive, diagnostic or curative purpose, i.e. that human experimentation is not planned. On the other hand, when new medicinal molecules are discovered, they can only be authorised to be placed on the market by demonstrating that satisfactory tests have been carried out on the human person. Legislation must therefore be strictly regulated because this issue opens up a legal and ethical debate.

Everyone agrees to acknowledge that experiments are fruitful and allow much more progress than the empirical tasting of past centuries. But the physical and moral integrity of the human being must be respected. For now, the situation is lacunar in our country, both for the subjects of experiments and for the members of the medical body who lead them.

The principles on which we have worked are as follows:

First, let’s define the human person. It is a person born, living and viable. So, all experiments on embryos in vitro, in utero or dead bodies do not fall under this bill.

Next, let us discuss the provisions relating to consent. Without prior consent, no clinical trials may be conducted. There are certain peculiarities for three types of people: minors, incompetent adults and those on whom an emergency intervention is taken and who can no longer give their consent.

The rules are different depending on whether the experiment takes place on a single site - it is monocentric - or on multiple sites - it is multicentric.

The issue of liability and insurance has been addressed. The promoter assumes, even without fault, the responsibility for the damage caused, whether it is directly or indirectly related.

Finally, the financial arrangements: there is no financial incentive but a few compensations.

This bill was inspired by two bills, one submitted by Mr. Thierry Giet and the other by Mr. by Philippe Monfils.

by Mr. Giet wanted to assert the lawfulness of experimentation and regulation of some aspects to protect the people who were entitled to it. The proposal requires the promoter to undertake an insurance that covers the responsibility of any participant.

by Mr. Monfils, on the other hand, specifies the conditions under which the research can be applied. During the general discussion, Mr. Monfils fully supports the bill but insists that the experimentation must be based on the latest scientific knowledge, aim at a scientific and therapeutic objective, and cannot be conducted without the consent of the human person.

He wishes that a general provision be provided concerning the non-profit character of the approach of the person who lends himself to the experience and that the King provide for expenses that may be the subject of financial compensation.

by Mr. Koen Bultinck is concerned because the scheduled deadlines for implementing the directive are short. The composition of the ethics committees is blurred and the objections made by the Order of Physicians and the State Council have not been sufficiently taken into account. This question deserves more reflection.

by Mr. Bacquelaine points out that the MR group is in favor of the transcription of the European directive. Our country has a successful pharmacological industry and medical advances are based on experiments. The bill must therefore incorporate the four principles recalled by the Bioethics Advisory Committee: the principle of relevance, the principle of scientific rigour, the principle of "primum noscere" and the principle of autonomy.

However, the question of consent must be considered taking into account the asymmetry that exists between the experimenter and the participant. Consent must be free and informed. With regard to ethics committees, the question of independence deserves to be raised, and when the tests are multicenter, it is wise to respect the 28-day period allowing them to submit their opinion. It is also important to ensure an exchange of information between the ethics committees.

Ms Avontroodt regrets that the transposition of this Directive was not carried out during the drafting of the Programme Act. We could have discussed it even more quietly. Like the mr. Bacquelaine, Ms. Avontroodt requests that the files be submitted simultaneously to all the relevant ethics committees. Ms. Avontroodt would like to distinguish between clinical trials with medicines and clinical trials without medicines.

The CD&V group by the mouth of Mr. Goutry joins the interventions of MR and VLD. Medicine should be at the service of man. He even suggests that research focuses on diseases that declare themselves in developing countries. He also insists on the independence and impartiality of ethics committees, as there could be a conflict between the academic world and the economic world.

For Ms. Doyen-Fonck, the bill lacked clarification in four areas: translation, definition, the fact that no distinction was established between sponsored and non-sponsored experiments and finally, the risks and side effects for the patient depending on whether the experimental methods are invasive or non-invasive. They ask the same questions about ethics committees.

Ms Magda De Meyer and Maya Detiège are concerned about the imbalance that exists between, on the one hand, the researcher, the promoter and the industry and, on the other hand, the subject.

by Mr. Yvan Mayeur welcomes the dedication of objective responsibility in the head of the promoter. He is not afraid of the independence of the ethics committees but rather of the increase in the workload that should strengthen the said committees. He finds interesting the clues to create a federal file of the census of healthy volunteers.

by Mr. Demotte, Minister, justifies the filing of this single bill regulating clinical trials and clinical trials. The rules must be optimal and identical, regardless of whether the research is medicinal or not. All the rules laid down by the Directive on safety and respect for the autonomy of participants, and the obligation of insurance are found in the text of the project. The only difference comes from the application of these rules to all the experiments. It should be borne in mind that drug trials account for more or less 70% of all experiments.

for Mr. The independence of the ethics committees is not questionable because the Royal Decree of 23 October 1964 specifies the rules relating to the composition and functioning of the hospital ethics committees. The rules for emergency experiments are based on the willingness to allow therapeutic progress for the patient but, as soon as possible, their consent must be obtained.

Mr. Speaker, Mr. Minister, dear colleagues, I thank you for your attention.

Mr. Goutry, as agreed, you are now reading the second part of your report.

Can I continue my speech after my report?

That is good. You submit the report and then submit your argument.

Mr. Speaker, Mr. Minister, colleagues, of course, I would like to thank Mrs. Colinia for taking the first part of the report into account. I also thank my colleagues committee members for agreeing to appoint an opposition rapporteur. For such an important bill with ethical implications, that is obviously appreciable.

The bill consists of 36 articles. I will try to summarize the article-by-article discussion and the progress of the voting on the various amendments using fifteen points.

The first point of the discussion was mainly about the composition of the Ethics Committee.

Both Mrs Doyen-Fonck of cdH and we of CD&V submitted amendments to include among the members of an ethical committee a pharmacist — or a hospital pharmacist in the case of drug experiments —, a general physician and a patient representative. We believe it is essential that they also belong to the Ethics Committee. Ms. Doyen-Fonck pointed out that in practice many committees already have a pharmacist among their members and that this was also mentioned in the opinion of the Bioethics Advisory Committee.

The second point concerned the requirement to analyze 20 protocols annually in order to be recognised as an ethical committee within the framework of the bill. An ethical committee is only authorized to carry out the tasks stipulated by law if that condition is met. Given the number, 20, according to CD&V is a previously arbitrary standard that does not provide guarantees for expertise, an amendment was submitted to remove that requirement. We do not want two types of committees. CD&V thinks in particular of smaller, regional hospitals. Mrs. Avontroodt wondered how the committees associated with the Scientific Association for Domestic Medicine can ⁇ that standard of 20.

The third point concerned the independence of the ethical committees. Ms. Doyen-Fonck had to make several amendments aimed at composing the Ethics Committee in a way that guarantees the independence and multidisciplinary competence of its members. One of those amendments means that the members shall, upon their appointment, provide a statement on the direct and indirect links with the sponsor of the study, with the exception of the non-commercial experiments. Members who, on the basis of that statement, do not prove to be independent of the client may not validly participate in the deliberations. That adopted amendment increases the guarantee of an independent ethical committee. With its amendment, the CD&V group sought to exclude from the vote the members in whom even a presumption of dependence existed. However, this was rejected.

The fourth point concerned the binding nature of the opinion of the Ethics Committee. CD&V submitted an amendment to express the binding character in the text. After all, the legislation speaks only of the condition of a favourable advice in order to be allowed to initiate an experiment.

The fifth point concerned the rules on discussions. Nothing specifies what majority rules play in the ethical committee to decide on a favourable opinion. Given the importance of such decisions in the context of experimenting on humans, CD&V found that the classical rule, half plus one, was not sufficient. However, the amendments aimed at ensuring that votes are held unanimously or at least by a two-thirds majority were not adopted.

A next point, colleagues, was about the clinical trials, the so-called drug experiments. A CD&Vamendement, to make clear that the term clinical trial is used further in the abbreviated form, trial, was unanimously adopted. Otherwise, one could erroneously see the word trial as a synonym for experiment in the broad sense of the word.

The next point, Mr. Speaker, Mr. Minister, colleagues, was the pilot phase 1. Both colleague Doyen-Fonck, the majority and CD&V submitted an amendment to replace the current definition with the definition corresponding to the terminology used by the International Conference on Harmonisation. This ICH definition is known in both the European Union, the United States and Japan. Since the CDH amendment was first submitted, it was therefore unanimously accepted for collegial reasons.

The next point concerns non-commercial experiments. Colleagues Doyen-Fonck, Mr. Mayeur and Mrs. Avontroodt asked the Minister for more clarity about who could be the client of a non-commercial experiment. Ordinary hospitals, non-university hospitals, psychiatric hospitals and, for example, the International Institute for Cancer Research are therefore excluded, according to Ms. Doyen-Fonck. According to Mr Mayeur, however, the amendment of the CDH, which includes an extension to the above institutions, goes too far. He requested an extension to non-university hospitals with a university profile and expertise in a particular research domain. Mr. Mayeur’s amendment was adopted allowing expertise centres to also act as clients of non-commercial experiments.

The next point is the publication of the research results. In order for the researcher to be able to publish his research results at all times, even if the client would rather not see them published, CD&V submitted an amendment to add that to the definition of the researcher. Only through publication can one share the acquired scientific knowledge with scientists worldwide. However, the Minister held that such a provision threatened to undermine the investigation in Belgium.

The next point concerns the additional definitions. In a memorandum of explanation, it is specified that experiments on the human person include the born, living and viable persons. CD&V noted that such an important description should not be missing in the list of definitions. The amendment was unanimously adopted.

The next point concerns the deadlines. Ms. Doyen-Fonck submitted an amendment extending the deadline for sending a reasoned opinion to the researchers. CD&V found that the time limits were significantly shorter than those laid down in the Directive. It was asked whether such sharply shortened deadlines would not compromise the quality of the opinions. The amendments therefore aim to align the deadlines with the Directive. Collega Avontroodt found that the ethical committee, which only gives advice, should have more than three days to disclose that opinion to the researcher. It also proposed that a copy be sent to the associated committees.

Mr. Bacquelaine submitted an amendment to send a copy to the committees associated with the locations where the experiment took place. That was adopted.

The next point was about the procedures to be followed, the conditions that must be fulfilled in order for an experiment to be initiated or continued. It concerned the provision that predictable risks and disadvantages must be balanced against the benefits. An amendment adopted by Ms. Avontroodt explains that these risks and disadvantages can be of both physical, psychological, social and economic nature.

Ms. Colinia submitted amendments to extend the articles on the protection of minors and adult persons unable to give permission with a paragraph stipulating that the risks for participants should be proportional to the benefits. The amendments were adopted.

When it comes to minor participants in an experiment, the ethics committee should have two pediatricians among its members. Mr Bacquelaine aimed with that amendment to improve protection. The whole committee approved the amendment.

CD&V submitted amendments to allow the request that a researcher who wishes to set up an experiment addresses to an ethical committee, by registered letter. Thus, there can be no dispute about the reception and the deadlines. Changes to the experiment shall also be notified by registered letter to the committees and to the Minister. However, the Committee rejected the amendments. The Minister saw it as an aggravation of the procedure.

Before initiating an experiment, the client must conclude an insurance covering the faultless liability for damages that the participant and/or his rightholders may possibly incur. Amendments were accepted by Mr. Mayeur. It stipulates that any damage directly or indirectly related to the tests must be compensated.

A restrictive contractual provision is considered void and the insurer can be sued in Belgium. In the case of a clinical trial, the Minister must communicate his objections to the client. In order to bring that provision into conformity with the Directive, CD&V submitted an amendment aimed at clarifying that there must be justified objections. The amendment was unanimously adopted.

The last chapter was about remuneration. There was also a long discussion about fees, contributions and salaries. In the provisions for the protection of the participants, Ms. Doyen-Fonck sought to include an annual maximum amount determined by the Minister of Public Health. The amendment was not accepted. Given the diversity of the experiments, the Minister considered it impossible to make a cost estimate.

CD&V noted that the Ethics Committee may determine the amounts to be or may be paid to participants and researchers. In order to ensure some uniformity in this, an amendment was submitted giving the King the possibility to determine the various aspects of which a compensation may consist. An amendment in that sense was not accepted.

The client is obliged to pay a contribution to the RIZIV when submitting a file. 25% of the amount will be spent on Public Health. The remaining 75% will go to the Ethics Committee.

The minister clarified that it would most likely be about a sum of about 1,000 euros. It is intended that for every 100 protocols the committee could have a level 1 employee and a secretary. It should be enough to have the client pay a sum of 1,000 euros for this and thus develop a self-driving system.

At the request of CD&V, the Minister further clarified that it is not yet certain whether each ethical committee will receive a basic amount, or, and if so, how the number of protocols will be charged. CD&V believes that the contributions paid by the client should not be paid directly to the ethical committee because then any form of control will be lost.

With the direct payment of the salaries, CD&V has no problem since those amounts are fixed by royal decree.

The amendment also means that the contributions of the client are not paid to the RIZIV but only to Public Health itself.

These amendments are rejected.

The Minister informs that the payment to the RIZIV cannot be changed as this is part of a compromise within the government. The distribution may be modified annually by a royal decree. Mr Mayeur’s amendment regulates that. The amendment of Mr. Mayeur is therefore adopted.

These are the main points of the article-by-article discussion with 108 amendments, of which 51 were adopted, 37 rejected and 24 withdrawn.

In the end, the amended bill was adopted with 11 votes against 2 abstentions.

Mr Goutry, thank you for your reporting.

Applause (Applause of Applause)

Mr. Goutry, I now give you the word to speak on behalf of your group. Whether the same applause will continue if you spoke on behalf of your group, we will see later.

I hope that the applause will be as strong. Thank you in any case for the great manifestations of sympathy.

Mr. Speaker, colleagues, I would like to briefly address a few concerns. We have explained them in detail in the committee, but we want to communicate this now because we want to abstain in the votes. This deserves some clarification.

It is clear that Belgium, like the other Member States, must transpose this Directive on the application of good clinical practice in the conduct of clinical trials with medicinal products for human use. We also support the conversion. That is, by the way, our duty. The legal protection of patients, subjects and doctors is necessary. The transposition of this Directive can address precisely these legal gaps in this area.

Nevertheless, we will refrain. CD&V is of course not against experiments on the human person, at least if they stimulate medical progress and if they work with respect for the subjects. Scientific and medical experiments are necessary. There should be no misunderstanding about this. We are in favor of medical progress. We also consider it necessary that people who participate in experiments are protected to the maximum extent possible. A law for the protection of test subjects is needed. There should also be no doubt about this.

Our points of criticism, our concerns, however, have to do with the way Parliament has developed that very necessary, important legal framework. The Directive dates from 4 April 2001. Member States had to adopt the necessary provisions before 1 May 2003 and the law had to enter into force by 1 May 2004. In 2001, 2002 and 2003 the government did not take any initiative. In order to ⁇ the entry into force before 1 May 2004, the Minister has now had to give up everything to prioritize this draft law and we were trapped in a row of too short time to be able to do this thoroughly.

The transposition of the Directive was handled too quickly. This is a draft of more than 100 amendments, of which 51 amendments were adopted. We have amended the bill of 34 articles 51 times. This is not a good legal work. This is rather a knotwork. The text was also not very good. There have been many linguistic adjustments. A large number of changes in the committee in a good atmosphere could usually be considered to toilets, but it is not good legislative work if one has to adjust a bill 51 times. This appears to have happened too quickly.

The draft legislation is much more than a mere transposition of the Directive on experimentation with medicinal products. It also covers all medical experiments on humans. It was not required. With this Directive, Europe only wanted to protect subjects in clinical experiments with medicinal products. We have only had a short time to treat this and then it is extended to all experiments. This is also a point of criticism.

This is also why CD&V has asked for a hearing, Mr. President, Mr. Minister, colleagues. The wide scope of the design, the social interest of this theme and its specificity require a thorough content preparation where consultation and confrontation with the people on the ground are imperative. However, there was, unfortunately, no time for a hearing. We left the design in the closet for three years and then we couldn’t even spend the time to hold an audition where we could have questioned people engaged in human experiments. Then we could have asked many questions to the people in the field itself.

In addition to our criticism on the quality of the text and on the course of the work, we still point out a few substantial remarks.

Scientific research must be at the service of man. Man must not come into the service of science—that is evident—so one must draw a boundary between what can and what cannot. Therefore, it is good that an ethical review should be done by an ethical committee. It is also good that such advice is binding, but in our opinion there is still too little independence for such an ethical committee. It would too often be possible for links to be created between the researchers who have to give advice, the people in the ethical committee who have to comment on such advice, and the sponsors and the researchers. We believe that the door should be completely closed. There has been an amendment adopted by colleague Doyen-Fonck that is important for the independence of the Ethics Committee, but we still find this too weak. We also wanted to include that even any suspicion of any connection between members of the ethical committee that should decide on that advice and the researcher or the sponsor should be disclosed. Such a member would never be able to participate in the voting procedure.

Second, the required 20 protocols to be able to give advice is ultimately a very arbitrary norm allowing us to get two types of committees, colleagues. We will have recognized and disqualified ethical committees. We will have smaller, regional hospitals that do not have a recognised ethical committee although they do excellent work, simply because they cannot meet the standard of 20 protocols per year. Rather, it is reserved for larger hospitals, university centers, and so on. We do not think this is a good technique. Nothing is said about quality with this quantitative standard. It would have been much better not to leave that in the design.

Third, it is incomprehensible to us that in an ethical committee of a hospital, which should advise on a drug experiment, a pharmacist or a hospital pharmacist is not required to have a seat. It is about an ethical committee in a hospital that must decide whether one can do a particular experiment with a medication in that hospital, while the hospital pharmacist is not required to be present in such an ethical committee. This cannot be for us. We do not understand the meaning of this, especially because in many cases the pharmacist will be part of the ethical committee anyway. We would have preferred to see it in order in the law itself to avoid all ambiguity.

Finally, Belgium may be stricter than what Europe imposes. However, we find that here we are unreasonably dealing with too short deadlines. We wonder whether this will not compromise the quality of the work. We refer here to the — in our opinion justified — criticism of, among other things, the Order of Physicians. The Order points out that the deadlines are unreasonably short and that they even involve risks with regard to the approval of protocols that will apply to experiments.

My conclusion is the following. The law is urgently needed. That is obvious. She should have been there three years ago. The law comes too late. As a result, we got too much to process in the short term and we may not have been able to discuss sufficiently thoroughly. We are in favor of good protection of test subjects. We are in favor of giving every opportunity to medical progress. Colleagues, however, there are too many blunders and there has been too little time to treat the bill properly. We will therefore abstain in principle.

Mr. Goutry, as you anticipated, there is a slight difference with the applause after your report. This, of course, does not change the relevance of your statement.

Mr. Speaker, Mr. Minister, Dear colleagues, Ms. Colinia and Mr. Goutry has already very well summarized what happened in the commission. I would just like to add a few additional elements. As you know, Belgium occupies a leading place in the field of research, especially in the field of medicines. This bill seems to be very important. It aims to provide guarantees for greater protection of the patient or participant in experiments, while setting competitive deadlines for the approval of the protocol.

Again, as Mr. Goutry, however, can be regretted that we are obliged to consider such a project promptly before the expiry of the deadline for the transposition of the directive into Belgian law, even though the European directive has been in place since April 2001. It is also regrettable that a bill with a wider scope of application than that of the European Directive is examined quickly and in precipitation, since it also regulates non-pharmacological experiments. The definition of experiments given in the law is very broad and, in our view, deserved a deeper debate, not for the transposition of the directive but for the extension of the scope to non-pharmacological experiments.

This regret is reinforced by the fact that we could not have a complete or updated opinion on the text of the bill. Indeed, the State Council, referred to in an emergency procedure, even acknowledges that it has not been able to undertake a thorough examination and in particular that it has not been able to verify the conformity of the text of the law with regard to the directive. Similarly, the Bioethics Advisory Committee has issued opinions on this topic, it is true, but some of these opinions are already old and otherwise do not refer to the preliminary draft or bill as such.

That being said, I acknowledge that the discussion in the committee was rich and constructive and that it helped to clarify some points. I appreciated the correction of the Minister, the Chairman of the Commission and colleagues who helped improve the text by accepting 51 amendments like Mr. Goutry recalled it, whether they are of the majority - which is logical - or of the opposition.

However, at the end of this legislative course, I have three questions, Mr. Minister, for which I would really like to receive your opinion before the vote.

The first concerns the guarantee of the independence of the ethics committees. Article 11 of the bill provides that, in the context of a multicenter experiment, the ethics committee that will issue the single opinion is chosen by the promoter. Hence, so written, it is clear that this brings exorbitant power to the experiment promoter – I recall that the promoter is most often a pharmaceutical firm – in the selection of the committee. This could lead to shopping from the promoter.

Furthermore, this provision in this sense does not provide sufficient guarantees for the independence of the Ethics Committee.

Finally, to remain consistent with the rest of the bill, I remind you that it is the investigator who delivers the file and not the promoter. It seems therefore logical that it is the researcher who also chooses the ethics committee. A second point I would like to return to: during the debates, I had raised the important question of what types of hospitals could be promoters of experiments or clinical trials. Indeed, the original bill was extremely restricted as it limited experimentation to only a few hospitals.

We had introduced an amendment extending it to hospitals, as defined in the Hospital Law, which was not adopted. The amendment then proposed by the majority was accepted; it aims to allow — I quote — “centres of excellence to be promoters.” Unfortunately, there is no legal definition of a centre of excellence, neither in this law nor in another.

It is true, Mr. Minister, interested persons will of course be able to go to see the parliamentary work to read the justification of the amendment that introduces this notion in the famous article 2. But, obviously, this does not simplify the reading and enforcement of the law. That is why I am talking about it again today.

I think that for a number of non-university hospitals, as provided for in the Hospital Act and which are currently research promoters, this definition is important. That is why I would like to wait for a moment.

I therefore refer you to page 31 of the report and this is the concept of the Centre of Excellence that I would like to clarify. A centre of excellence shall mean a service such as: 1° an approved center in bio-security, thus capable of carrying out phase 1, 2 and 3 studies in relation to the GCP; 2° a center which has a trained and experienced staff, including doctors, bio-statistics, etc.; 3° a center which has hospital structures suitable for participants in accordance with Directive 95/46; 4° a training centre for other professionals in human experimentation.

Mr. Minister, can you confirm me that this is the definition you give to the centers of excellence?

If so, and I imagine that is the case, don’t you find it more rigorous to provide for the definition itself in the law? Do you really believe, Mr. Minister, that interested persons, who will have to refer to it, will consult the famous paragraph on page 31 of the report? Allow me to doubt.

Finally, I would like to emphasize one point that is problematic to me and which we have not discussed in the committee. I raised this point after reviewing the report – and I remind you that we could not reopen the debates at that time – as well as after several readings of the bill.

Article 7(2) of the European Directive provides that “In the case of a multicenter clinical trial carried out in several Member States at the same time, there are as many single opinions as there are Member States concerned by that clinical trial.” This paragraph of the European Directive is not transposed into the draft law. Does this lack of transposition not pose problems in the interpretation of this law? Let me insist on this point. In the event of a multicenter experiment project whose application is submitted in another country of the European Union and since the sponsor is in possession of a single opinion submitted in the country where the experimental protocol was introduced, what prevents the researcher from starting a multicenter experiment also on a Belgian site since he will be in possession of a opinion recognised by the Ethics Committee? In fact, the bill does not stipulate that the ethics committee in question must be Belgian. Per ⁇ , Mr. Minister, you will answer me that these committees are defined by reference to laws whose scope of application is limited to the Belgian territory. But this could obviously be interpreted differently; it is also well specified and taken up within the Directive.

In conclusion of these three points, I think that if we had more time, we could have taken the effort to request additional opinions in order to remove these last hesitations.

Mr. Minister, I have submitted amendments on the three points I have just addressed and I hope you will give a precise answer before the vote. However, it is true that this bill is important because it concerns, above all, the protection of patients and participants in experiments. It is also important because it provides pharmaceutical companies and researchers with a framework that facilitates clinical trials and trials, thus enabling them to develop effective and innovative medicines and care techniques in the service of patients.

Subject to the questions I have just asked you again, Mr. Minister, our group will support this bill because I believe that the great winner of all this is the patient, the patient and again the patient!

Mr. Speaker, Mr. Minister, my dear colleagues, for my part, I want to say, from the beginning, that I do not feel like I have participated in a quick and hasty discussion.

I had, of course, also expressed the regret that we did not transpose this directive faster, that is obvious, but the multiplicity of European directives makes that we do not always have the possibility to follow the pace at the desired speed.

The debate took place in serenity and allowed everyone to express their point of view. No matter what the subject matter is, a project is never perfect. To demand perfection is to put a brake on all evolution and on every possibility of adopting plans. If you expect a project to be perfect for adoption, you will never adopt it.

Everyone was able to express their views during the discussions. Proof of this is that a large number of amendments have been adopted, which undoubtedly testifies to an active and constructive discussion.

It is up to the legislator to transpose into our legal order this famous directive dedicated to clinical trials of medicinal products. The Government’s choice was to extend the consideration of this Directive to other types of experimentation, to everything that affects medical progress and involves human participation in studies. Thus, we fill a number of gaps in our legislation and ensure the uniformity of the regulations on human experimentation.

Research plays a crucial role in the development of medicine. We all know that it is impossible to advance in the medical field unless rigorous research is carried out — first fundamental, then animal, and finally human person — before putting techniques or medicines on the market, to benefit the greatest number, in any case, all those who need them.

An ethical question immediately arises in this type of problem that is the protection of the patient or subject who agrees to submit to an experiment. As part of the discussion, there was also interest in the performance of our pharmaceutical industry, our technology industry. It was necessary to preserve the interests of the subject who submits to the experiment but also to ensure the continuation of an effective and performing technological and pharmacological industry in our country. I think we have achieved this double goal.

Some say it is sometimes delicate to mix an ethical concern — that of patient protection — with an economic concern — that of ⁇ ining an efficient industry in our country. I do not think so. On the contrary, I believe that there can be synergies between these two objectives. Moreover, the pharmaceutical industry is not just an economic problem. The more we benefit from technological investments in our country, the more chances we have to advance the care offered in our hospital institutions. The proximity between this pharmacological industry and the care distribution network is a favorable factor for the patient and at the economic and social level as many jobs are affected.

It is often said that in order to promote employment, we have an interest in prioritizing investment in technology. This is a weakness of Europe compared to the United States. It is therefore important that we can, on the one hand, promote these investments and, on the other hand, promote the creation of jobs in companies that “cling” to the territory, that is, that invest, develop in an environment close to our academic centers and our research centers.

We wanted to ensure the protection of participants in the experiments. The quality of the text has been improved in many articles by the accuracy of terms and the scope of provisions. For example, in Article 5, we submitted an amendment to clarify the type of predictable risks and disadvantages that must be assessed before proceeding with the experiment, clarifying that these were not only physical and psychological risks affecting the medical material and the person but also social and economic risks for the participant. Similarly, for the notion of consent, to which we were strongly attached, it has been specified, ⁇ in the context of experiments that engage incapable and adult persons.

It was also important to develop the modalities of compensation for participants in the event of injury, trauma and death. I think it was useful to clarify the principle of objective responsibility that will prevent the patient and his rightful successors from proving guilt in case of injury or, more generally, of damage resulting from the experiment. The green light given by the ethics committee obviously does not exempt the researcher from his responsibility and it is the promoter of the experiment that incurs the responsibility of the latter.

As part of our committee work, we have expanded and clarified the scope of the scope of the promoter’s responsibility. The final draft provides that non-fault liability will extend to all medical care and acts directly or indirectly related to the experiment. Consequently, it is also provided that the insurance covers all damages related directly or indirectly to this experiment. If a medical error is committed in the context of treatment related to the experiment, the participant may be compensated without having to prove the error or causality.

We also welcome the fact that the Ethics Committee is required to report, in its opinion, the reality of the subscription of this mandatory insurance by the experimenter.

Finally, we also created a real direct action of the participant or his rightful successors against the professional RC insurance company of the promoter. I therefore think that all guarantees have been taken in relation to the potential risks that a participant in a clinical or technical trial could take.

We also wanted to preserve the conditions for research development. As I said, these were the two goals pursued: preserving the interest of the patient and preserving companies dedicated to the development of new technology products. We therefore preserved the interests of research by limiting in time the faculty left to participants who terminate the experiment to require that the data concerning them and obtained through this experiment are not used. This is important, of course it is necessary to give a sufficient incentive to the promoter of a research so that he can effectively use the results of that experiment.

We also shortened the deadlines. I hear the criticism of the Order of Doctors in this matter, but it seems to me that the deadlines as they are planned, i.e. 28 days, seem reasonable. We do not ask the Ethics Committee to conduct a pre-research. We should not confuse the tasks. We ask the Ethics Committee to take into account the principles that are also issued by the Bioethics Advisory Committee and which rely on the principle of relevance, for example, the principle of justification of research in relation to the potential benefits and disadvantages.

It is therefore an orientation that the Ethics Committee must take in relation to the preservation of the patient’s interest. He is not asked to do a study before the study. This concept must be considered in such a way that in the field of pharmaceutical research, our industries are encouraged to promote research in our academic institutions or in the research institutions of the country. This is one of the characteristics of our country in terms of pharmacological research and we must preserve it and ensure that this niche continues to benefit all research in our country.

I would also like to emphasize the results achieved in the association of ethics committees. From time to time, I hear criticism about the independence of our ethics committees. I myself raised this issue at our meeting. Nevertheless, I hear well the proposal of the Order of Physicians that would prefer that the researcher designates the ethics committee, rather than the "industrial" promoter. The fact of proposing this puts into question the integrity of the Ethics Committee. Let’s be clear: if one thinks that the promoter could prefer through arrangements with an ethics committee, preferring one or another ethics committee, it is that the integrity of the ethics committees is questioned.

For my part, I do not think I can do it. On the one hand, I have no evidence indicating that these ethics committees would not be integral. On the other hand, I rather feel that their composition ensures that integrity. Furthermore, if one questioned the integrity of these ethics committees, one should do so on the whole line and not just on their designation by a promoter. Indeed, designated by others than by the promoter, one could imagine that they could then be subject to pressure from the promoter after the designation. It would not be difficult for a promoter to find "modus operandi" with an ethics committee, once it is designated by an investigator. This argument does not hold the way from the moment when it is considered that the ethics committees in our country demonstrate a great integrity and intellectual honesty which I think has been acquired.

On the other hand, and I thank the committee for taking this argument into consideration, I would have wanted to have taken into account the need to involve as much as possible the ethics committees of the centres that are not responsible for issuing the single opinion. At all costs, the ethics committees should be avoided. Where clinical research is partially conducted, I find it useful that the ethics committees of these institutions can be associated with the implementation or development of the single opinion of the committee chosen by the sponsor.

It also seems to me that the circulation of information between these different ethics committees is absolutely necessary so that everyone feels invested in a mission and feels concerned by the studies carried out in the centers of our country in terms of academic or scientific research. I also hear some arguments regarding the centers of excellence.

I agree with the wording of this amendment. Why Why ? I think we need to be flexible in this area. Thus naming, from now on, in a law or specifying very particular targets for centers that would be allowed to carry out the non-commercial experiments and by default, the centers that would never be able to carry them out, seems to me to fix the situation in a manner somewhat damaging in terms of evolution of the structures to which it is possible to entrust experiments.

Also, I think that the definition we have adopted is the right one and that we will have, thanks to it, the possibility to maintain some flexibility in choosing the centers of excellence that will be able to carry out these experiments. There are institutions that we want to target. I think in particular of Brussels institutions such as Brugmann and others, the CHU of the Citadel in Liège and Mont-Godine in the province of Namur. However, it was not necessary to name them. On the contrary, it was important to maintain a certain flexibility in the matter depending on the evolution of things. Institutions are not always what they were and they will not always remain what they are today. I think that flexibility is necessary.

In conclusion, the MR group will of course vote for the transposition of this European directive and the extension to any human experimentation, medical, pharmacological or technological, considering that this is a progress both for the patient himself and for those who dedicate themselves to research in our country.

Mr. Speaker, Mr. Minister, colleagues, this bill is ⁇ not banal. On the contrary, it is extremely important that the Minister has approved the draft in time and that the discussion has gone fairly smoothly and with a very large openness to the members of the committee.

The ethical legitimacy of clinical trials has long been out of question. The Advisory Committee on Bioethics has formulated it as follows: "The biomedical experiment with humans has an important place and a great influence on the advancement of medicine during the twentieth century." This means that in the discussions sometimes held in certain media around the ethical responsibility of human trials, it is forgotten that without the clinical trials progress would not be what it is today.

There is a field of tension between the individual interest and the general interest. The fragile balance exercise that can be found in the bill is a successful exercise. However, I must admit that in extremis quite a few corrections and improvements have been made to the design. It is the merit of the President of the Commission that this has been possible. The date of 1 May 2004 had to be fulfilled. Mr. Speaker, also thanks to the fact that we were able to discuss the draft today, we can reach the predetermined date. This is ⁇ one of the most crucial points of the design.

My colleagues have already said that in Belgium we are a centre of excellence in the field of clinical research and medical research. I give a few figures. There are 26,000 people working in the pharmaceutical sector in Belgium. Of these, 7,000 were recruited in the youngest 10 years. Of these, 3,600 people work exclusively in research. This is an added value for society. This is an added value for public health. That is an added value for health care in our country, colleagues.

Therefore, the design and the possibilities to anchor the clinical trials in our country today are of much greater importance than one would eventually think.

Despite the amendments, I think there are still two pain points. The first pain point is, of course — which will become clear on the ground — that the composition of the ethical committees is not very concrete. Usually, this does not cause problems in the field. However, if the law was modified, it might have made it even more clear, even in terms of independence. However, I do not belong to those who would not have confidence in it, on the contrary.

The second pain point remains a tension field. This is about the difference between commercial and non-commercial testing. Since the draft ultimately aims at the protection of the individual, it is, in my opinion, from an ethical point of view — since both types of trials contribute to innovation and to innovative medicines — that a difference in approach between commercial and non-commercial organisations for the reimbursement of whether or not to make medicines available free of charge is not immediately justified. After all, just the responsibility to conduct a clinical trial is ethical and aims to make progress. Whether it is financed for a commercial purpose or not is irrelevant. I had the opportunity to be present at the European Summit on Innovation, which took place in the Brussels Sheraton hotel.

It was stated very clearly that if the industry did not invest in innovation and research, more than half of the medicines today would not exist. In the north, and even in Norway, a country known to be high-profile in solidarity, much more space has been given to the industrial and commercial aspect. The reconciliation of both factors, I think, will only increase this in the long run and the added value for society, the return on investment, will be much greater for progress.

The protection of minors and of people with disabilities is of course very positive, as is the guaranteed insurance. My colleagues have already mentioned this enough.

Mr. Speaker, Mr. Minister, colleagues, I think there was good work done in the committee meetings and there were many possible adjustments. Despite the initially heavy criticism that there was too little time and that the expansion was too large, I think that the debate, the report and the responses of the Minister at the committee meeting were very important to remove the unrest that still exists, especially in the biotechnology and bio-industrial sectors. This is due, among other things, to the fact that the Minister has accepted the amendment aimed at allowing the list to be resolved without having to amend the law or without having to draft a new law. Also in view of the concerns expressed by the VIB, the Flemish Institute of Biotechnology, it is very important that this amendment was accepted. All this was a very good first exercise to create a solid design.

Mr. Speaker, Mr. Minister, Dear Colleagues: "The history of medical experimentation coincides with the progressive learning of the appropriate way to experiment on humans, both at the methodological and ethical level. The use of human testing is justified only in the event of clinical uncertainty. The experimental methods have been gradually refined. These scientifically well conducted experiments are much more fruitful in terms of the advancement of knowledge than the simple empirical tasting of previous centuries. Therefore, there is a duty to experiment in order to provide the sick with the best knowledge and the best treatments.”

This introduction, drawn from the report of Opinion No. 13 of the Bioethics Advisory Committee on Experiments on Humans, defines well the entire framework of the bill that is presented to us today, and the importance of the work that has been done by the Minister and Parliament.

Indeed, if the legitimacy of scientific medicine is acquired today, the legitimacy of human experimentation is not obvious not only because there is still a risk of instrumentalization of the participant, but also because it opens an ethical and legal debate, especially given the shortcomings of the current legal framework that we amend.

Under Belgian law, medical intervention is only legitimate in the interest of the patient and only for preventive, diagnostic or curative purposes. Human experimentation is not planned on the legal level even though it takes place every day in our country.

However, this situation is contradictory not only with the duty to experiment provided for by medical deontology, but also with certain elements of law, in particular in the field of new molecules of medicinal products which can only receive marketing authorisation by demonstrating that satisfactory tests have been carried out on the human person. Others have said it before me.

There is therefore a legal void that is detrimental to both the protection of the persons entitled to the experiment and the doctors who conduct it. Indeed, a doctor could currently be prosecuted — this is a bit absurd — for beats and injuries while practicing an experiment, which is, of course, no longer at all relevant.

The legal situation was therefore lacunar and, therefore, created a state of insecurity for both the subjects of the experiment and for the members of the medical body.

Directive of the European Parliament and of the Council of 4 April 2001 on the approximation of regulatory legislation, etc., between Member States, on the application of good clinical practices in the conduct of clinical trials of medicinal products for human use.

I would like to welcome here, as other colleagues have done, the fact that Minister Demotte allowed the transposition of this directive to be done by a law and not by a few lines in the loiprogram or a royal decree, as his predecessor had imagined.

It is true that we had to work quickly to meet the deadline of 1 May. Per ⁇ some colleagues had to suffer from this urgency, but what would we have had as a parliamentary debate, if we had to instruct this case as part of the loiprogram or a royal decree? I think there would have been no debate. I would like to thank you for allowing this discussion.

I also welcome the fact that this project is also inspired, for a part that does not fall within the scope of the European Directive, by legislative proposals that have been submitted: that of Mr. Monfils, that of my colleague Thierry Giet, who had also cared about providing a legal framework for human experimentation. Some of the elements of his bill are also taken into consideration in the bill that we are going to vote on.

The subject matter is important since Belgium is very active in the phases of the clinical trial and is internationally renowned for its know-how in the field.

The Directive concerns exclusively the field of medicinal products. The project goes further, as it also defines legal rules for the protection of individuals who undergo human experimentation.

The novelties that the directive brings compared to current practice can be listed as follows: the favorable opinion of an ethics committee, the directive requires a single country-by-country opinion for multicenter tests, the directive formalizes the protection provisions applicable to minors and disabled persons, it requires the promoter of an experiment to have an authorisation from the Ministry of Health. Finally, deadlines are set for the Ethics Committee and the competent authority to take a decision.

For my part, I stressed in a committee that the government could have preferred a limited approach to drug experiments. But this option would probably not have been the most satisfying, since it is undeniable that academic research and industrial research blend into each other.

The decision to authorise the conduct of experiments in emergency situations must be taken within a well-defined framework. It should be aimed at improving the patient's condition and can only be carried out if current medications do not immediately treat the patient's condition and bring him an improvement. But it is still important and interesting that, even in emergency situations, the bill allows experimentation on patients.

I would also like to note the dedication of an objective responsibility in the leader of the promoter. This is an important step forward for us as we are supporters of a generalization of a system called “no fault”. As recalled in article 29, as cited recently by my colleague Bacquelaine, the responsibility for the damage caused to the participants is assumed by the promoter. Whether the damage is related to experimentation, directly or indirectly, is a considerable advance. Prior to the experimentation, the sponsor must contract an insurance covering this responsibility, otherwise the experimentation cannot take place. This seems to me to constitute important guarantees provided through the bill and going in the direction of what we want more generally in public health.

Like other colleagues, I was concerned that the bill reserves the faculty to give a single opinion to ethics committees that demonstrate having analyzed at least 20 protocols a year.

What can be, indeed, the consequences for committees who cannot provide this proof? Can the ethics committees associated with the competent committees claim their intervention for the accounting of the analyzed protocols? The Minister was reassuring as he confirmed that Belgium has a sufficient number of ethics committees with sufficient expertise to make the law applicable. Indeed, at present, of the 80 ethics committees that spontaneously submit to the Bioethics Advisory Committee a report of their activities, it appears that half of them analyze at least 20 protocols per year and thus comply with the prescribed law.

As for the associated ethics committees, their opinions will be accounted for the calculation of the protocols currently analyzed. We can look forward to this opening that will allow small ethics committees to gradually meet the obligation to analyze 20 protocols per year as provided by law. As well as the choice of shorter deadlines than those of 60 days fixed by the directive, which tends to maintain Belgium’s competitive position but which is also inspired by public health considerations, since the shorter deadlines will allow citizens to benefit quickly from the latest therapeutic innovations, it seems to me a reasonable choice made by the government in this regard.

Finally, the independence of the ethics committees is, in my opinion, not threatened. I do not see how the very fact of being a promoter and being the ethical committee chosen by the promoter would jeopardize this independence. There are people there who work seriously in the interest of research, public health. They have been carefully performing their duties for many years already, without any jurisprudence suggesting that their sense of responsibility must be subject to suspicion. On the contrary, these ethics committees work seriously. Tomorrow, they will obviously have more work and they will, in addition, in this regard, be financed by the provisions provided in the bill. It is adequate. Financial arrangements aimed at strengthening the human resources of the committees, in view of the increase in the workload resulting from the application of the law are provided. It was necessary.

It also seems to me essential to emphasize that the minister who, in some cases, must give his prior authorization to an experiment, cannot intervene in the field of ethics. This is formally prohibited. It is the role of the ethics committees and not the executive to intervene in this matter.

In order to avoid this interference, it was appropriate to circumscribe the ministerial intervention as best as possible. Some might think that the bill leaves too wide discretion; personally, I don’t think so. The fact of allowing the Minister to decide exclusively on the quality of the medicinal product, referring in this regard to the instances generally authorized to do so, limits the scope of the intervention of the executive and political power in a matter that must remain free and which must not suffer from any partisan intervention. Research must be as free as possible in the interests of humanity and public health.

I would like to say a word about the amendment I submitted, which aims to amend article 2, 15° of the bill with the aim of allowing centers of excellence to act as promoters of non-commercial experiments. Mrs Doyen-Fonck and Mr. Bacquelaine intervened on the issue. Of course, I share their views. It is necessary to allow those who are not academic but who have recognized expertise – I have cited; but I cannot do otherwise, a hospital I know well: the CHU Saint-Pierre, which currently conducts research expertise for an AIDS vaccine – to continue their work. Imagine that this research could no longer intervene in Belgium, because it is not carried out directly by an academic institution, would have been an aberration. As other colleagues have said, other hospitals, tomorrow, in the north or south of the country, may also be led to conduct an interesting experiment, in a sharp way, on a subject. The government should be flexible to adjust the law. The Minister will therefore have the competence to recognize centres of excellence according to certain criteria because, of course, serious guarantees are needed in terms of research. We can therefore open the door to centers of excellence that also carry out research.

Nevertheless, we have been able to do an important job within the commission. Many amendments were approved, a sign that the debate and dialogue with the Minister was quite open and that we were able to work together. Amendments have often been the result of a collective work of the commission: majority, opposition, government bank. The general interest prevails. We had an extremely rich parliamentary debate, and I look forward to it. The bill provides guarantees for participants in the experiment and safeguards the interests of companies, researchers and universities in our country. So I think that we met both the European objectives that were assigned to us but also the interest of our public health system.

We will be able to gain a lot of time for all of us. The debate in the committee was perfectly reflected by those who made the report but also enriched with the added value of the speakers who came here, in pointillistic touches, reminding what are the enamels that give colors to this text, colors that did not come out only from the pen or brush of a minister or a government. You see, here I use the vocabulary of the former Minister of Culture that I am! I now approach you under my hat as Minister of Health to tell you that this matter is consensus.

What is the goal we are pursuing together? Is this an experiment on humans? The answer is no. What we are pursuing is not experimentation on humans, it is the improvement of the quality of human life. That is why I have never, in the proposals that have been made in committee as in the reflections that have been repeated here at the tribune, found an offence to this principle. The openness I have shown is also based on the quality of the interventions and the enrichment that each of you has allowed to bring to this text.

Since we agree on the principles, I do not need to recall them, I will rather give some elements which, I hope, will answer the question points that still remain suspended today in the text. One of these question points concerns the delicate issue of defining the independence of ethics committees. I am not going to play the one who will prequalify this independence. I would like to emphasize that these ethics committees have already existed for some time. These ethical committees, made up of high-quality men and women, have so far not been the subject of criticism of the style: "We have observed in concrete behaviors the deviations, abuses that today would have lit an alarm witness which we should take into account."

Nevertheless, since man is still suspicious of man, we have also provided in this text a number of balanced measures. To begin with the most important to ensure the autonomy and independence of these opinions, these are the financial means. On this subject, I would like to bring a little information to those who, having not attended the meetings of our commission, do not know. We have established a methodology of means that distributes a 75/25 key — you will see it in our text — between the part that will serve the general oversight of these ethics committees and concrete field work. Ms. Avontroodt told us, very wisely, that it would be useful to imagine that these keys could vary at a given time. Therefore, we have planned possible evaluations.

The second element outside of funding is the question of composition. On the composition of the ethics committees, what do we say? We say, of course, that they must be made up of men and women of great expertise, as was already the case, and I hope to do so again tomorrow. The other element that was highlighted is that of the distinction between the expertise that one brings and the interests to which one could be confronted directly or indirectly depending on his position. We stipulated in this text that not only could one no longer formally participate in deliberations in relation to which one would have a direct or indirect interest but, in addition, we have put in place – and this is still an enrichment brought by the members of the committee – the proposal of a declaratory act which makes it possible to say a priori whether or not one fears this confusion of interests at one time or another.

The question remains how the choice of ethics committees can be made in certain circumstances, where indeed, for example, one is faced with experiments that are implanted in several centers. We have established a hierarchy. First, for the monocentric experiment, the evidence is there: it is the ethics committee that is in relation to the place where the experiment is done. In multicenter logic, we have created a logic of hierarchization that provides three stages.

First, if among the sites there is an academic hospital or a monodisciplinary university hospital, the sponsor must address his request to the ethics committee of one of those hospitals. We have already talked about it, and I will not return to it.

Secondly, if none of the sites is one of the hospitals covered by cidessus but is nevertheless a hospital site, the sponsor must address its application to the ethics committee of one of the hospitals concerned.

Finally, if none of the sites is a hospital, then the promoter will submit its application to the ethics committee of one of those sites. There is therefore an element of choice. If they do not have one, they must address their application to a competent ethics committee which may, by protocol, be bound to the experiment.

I would also like to say that the choice of the promoter, not the researcher, is a choice that we have made for a functional reason. In monocentric experiments, the problem does not arise. On the other hand, in multicenter experiments, we do not have a set moment in this text of multicenter researchers or coordinators of these investigators. That is why we remained at this choice of the promoter.

The theme of the centers of excellence.

I have no difficulty in confirming the interpretation given in commission by the President when he had to give a few examples of what he meant by centre of excellence. I remind, however, that while not refuting these elements, we will approve these centers of excellence through the King, which will allow further revision in final. Regarding the last observation on the more specific subject of the non-transposition of Article 7, §2 of the European Directive, I must recall that we do not have the legal faculty to do so. Indeed, what Europe says is clear: it says that when counseling needs to be sought at the national level and from multicenter experiment centers, only one must be granted. Consistency depends on it. It is also true that in the case of experiments taking place in several countries at the same time, the Belgian authority has no competence in domestic law to go to regulate the way this happens outside our borders. Therefore, we are carrying out an exercise of transposition into our law. As you will have understood, this is why it was impossible for us to go beyond the measure we ourselves took.

I would like to end with the members of the committee and thank the services for their cooperation. It was a first opportunity for us to build a text together. It was a real pleasure for me.