EAHP 2012 Report – Interview with Dr Chantal Bélorgey

Zara Qadir interviews Dr Chantal Bélorgey (pictured), Head of Clinical Trial Development at the French national competent authority, Affsaps (Agence française de sécurité sanitaire des produits).

What is the difference between off-label use and compassionate use?

The compassionate use is the use of a medicinal product, which does not have any marketing authorisation. Although, the off-label use means that there is a marketing authorisation but the use is outside the indication.

For example, you may have a marketing authorisation in colon cancer, and you want to use the drugs in lung cancer, that is off-label use. The compassionate use is where there is no marketing authorisation at all for the drug. So in that situation, either it is, a product, which is being developed, which is clinical trials or it’s a drug that is authorised in another country, but not in yours.

What is an ATU, and what are the general principles of granting an ATU?

The ATU is the authorisation for temporary use of a drug that does not have marketing authorisation in France. It is the French system of compassionate use, and this system is mainly characterised by the National Competent Authority giving a pre-authorisation to use a drug for one patient [nominative] or a group of patients [cohort].

There are a several criteria to grant this authorisation. First, the drug is intended to treat a patient but not to investigate or to confirm or demonstrate the efficacy or the safety of the drug. Second, the disease must be a rare or a serious disease. Third, there is a condition that there is no therapeutic alternative for that patient. The forth reason is that there is some data that demonstrates the efficacy and the safety of the drug.

The level of the benefit/risk ratio might be different between a nominative ATU and a cohort ATU meaning that sometimes in the nominative ATU, you might only have a presumption of efficacy and safety, although for the cohort ATU, there must be a high presumption of efficacy and safety.

How does it differ from a Clinical trial?

The ATU system is really different from a clinical trial. The main difference is in the objective. The objective of an ATU is to treat whereas the clinical trial is to demonstrate or confirm the efficacy and safety of a drug. For an ATU, there must be some data available on efficacy and safety.

Although for a clinical trial, for the first phase in humans, you may not have this kind of data available. The regulatory system is very different, but the clinical trial is under the scope of a Clinical Trial Directive, where there is a need to have firstly an authorisation from the Competent Authority and secondly a positive opinion from an ethics committee. Third, the GCP rules must be applied, and there are a lot of very strong rules to conduct a clinical trial including rules for safety reporting, which might be different from the ATU.

Could you summarise the impact that the ATU system has had in France over the last fifteen years?

The first impact is that is allowed the access of new drugs for people who are in therapeutic dilemma, where they have no treatment options anymore.  An ATU is a way to offer new treatment to very serious patients. For example, we have offered all the AIDS treatment during the last fifteen years sometimes one year before the marketing authorisation.

For rare diseases, drugs that are not authorised under the marketing authorisation system have been offered to French patients in the ATU system, sometimes more than 2 to 3 years before marketing authorisation. Seventy percent of these products have been offered through the ATU system in France. I would say, that the access to new drugs for patients with very serious conditions, has improved and accelerated through this new system.

Why the need for the new rule changes to the ATU system? How does an RTU differ?

It is important to analyse the experience of over 15 years, what we have seen is that the cohort ATU, is a very good system, not only to give access to drugs, but also to monitor people who are treated. However, the nominative ATU might last too long, and it is not really a temporary situation. We would like to change this, because by definition the ATU is temporary.  We see some drugs in nominative ATUs, which stay always in this status, and we would like them to come to a marketing authorisation.  We need to focus and decrease the scope of the nominative ATU, while we want to in parallel to increase the facilities to open clinical trials, and to get marketing authorisation later.

So, we are going to change the criteria, that before being offered a nominative ATU, a patient should be offered inclusion in a clinical trial.  For that, we need to develop clinical trials in France more and more, and we are thinking of developing new systems in order to develop these clinical trials.

How can the French experience guide other European countries in Clinical practice?

So the system in France is fifteen years old, but we now see in other countries similar systems.  For example, in Germany, Spain, Sweden and Portugal, and what these member states are taking from the French system is the cohort ATU system. I would say that, we will influence the way that the ATU cohort is being developed in another member states. Most of the member state countries are developing this kind of system.

What would be your take home message for hospital pharmacists?

The system is really based on the support from the hospital pharmacist. Pharmacists are the ones, who are the link between the physicians, and the AFSSAPS.  When we have a problem, or we need further information on a patient, we call the pharmacist. We don’t call the physician. The hospital pharmacist is the only one who can distribute or supply the drug. Also, they are involved in the protocol of therapeutic ATUs, which will be mandatory for all the drugs in the ATU system, because they are the ones who supply and deliver the drugs. Also, hospital pharmacists are involved in the pharmacovigilence system and circulating information on the drug. Hospital pharmacists are the link between AFSSAPS, physicians and patients.

Where can we find more information? Are there any other developments?

There is a lot of information on the AFFSAPs website. For example the process for the nominative and cohort ATU, as well as protocols for therapeutic ATUs for all the drugs, and lists of medicinal products which are available on cohort and nominative ATU. Also, we have developed information on hospital preparations. Hospital pharmacists sometimes manufacture preparations. We give information about how these preparations can be replaced by medicinal products, which are available under the ATU.

AFFSAPS are developing the ATU system, and securing the safety of patients further.  We are also developing an off-label use system, which will be similar to the cohort ATU as we will monitor all people being treated on an off-label use basis.