"Dramatic side effects are rare"

Christiane Fux studied journalism and psychology in Hamburg. The experienced medical editor has been writing magazine articles, news and factual texts on all conceivable health topics since 2001. In addition to her work for, Christiane Fux is also active in prose. Her first crime novel was published in 2012, and she also writes, designs and publishes her own crime plays.

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In France, five healthy men suffered severe cerebral haemorrhage after taking a new drug, and one died. Nevertheless, such tests are indispensable, explains Dr. Rolf Hömke, press spokesman for the Association of Research-Based Pharmaceutical Manufacturers, in an interview with

Dr. Rolf Hömke

Dr. Rolf Hömke is press officer for the science press at the Association of Research-Based Drug Manufacturers (VFA).

Dr. Hömke, the incident in Rennes, France, is tragic, especially because the men were very healthy before taking the active ingredient. How can drug research ethically expose healthy people to potentially fatal risks?

First of all I would like to say: We are dismayed by what happened to the participants and hope that the four victims who have been treated since the incident will soon be better.

In response to your question: Medicines are developed to help sick people or - in the case of vaccines - to protect healthy people. This is the only fundamental justification for exposing people to risk. It is the task of ethics committees and drug authorities to decide on a case-by-case basis, which must review and approve every study with humans before it can take place.

What is being done to protect drug trial participants?

There are strictly regulated approval procedures for the studies. The most important thing is: every new active ingredient or auxiliary substance must not come into contact with people at all. A whole series of prescribed tests with cell cultures and various animal species go ahead. Everything that is conspicuous is discarded. This means that a whole range of substances that would also cause problems to humans are out of the running.

The path from the idea in the laboratory to the approved drug takes an average of more than 13 years. About halfway there comes the point at which the first person has to take the new drug. And if at all possible, it should be a healthy one.

Why not someone who already has the disease in question? He would at least benefit from such a drug right away.

In some cases it is actually done that way. With some cancer drugs, for example, tests are carried out directly with patients if severe side effects such as nausea or hair loss are unavoidable during their use. That would hardly be reasonable for a healthy person. A seriously ill person, on the other hand, might say to himself: "Better a drug that shakes me up but might help than no chance." However, it is usually preferable to test a new active ingredient on healthy people first.

Why?

There are many reasons for that. In tests with sick people, for example, it is more difficult to tell which symptoms are due to the disease and which are due to the new active ingredient. Above all, however, we can only get to know the normal situation with healthy test persons: How quickly does the active ingredient get into the blood after ingestion? How high is his concentration there then? How quickly is the substance excreted - and does this mainly take place via the kidneys or the intestines?

So animal experiments are not enough to clarify this.

Most of the time, a substance actually behaves the same way in humans and animals, but there are sometimes deviations. They do not necessarily play a role in tolerability in healthy people, but they can cause problems for sick people. For example, many diabetics have damaged kidneys. Then it is important to know in advance that an active ingredient will stay longer in your body.

How meaningful are animal experiments then?

Evaluations over decades have shown that about 70 percent of the side effects are found in animal experiments that would later also occur in humans. So: the majority of the problems can be seen and intercepted, just not all of them.

So almost a third of the side effects go undetected because they do not occur in animals but only in humans?

That's right.

How often do such undesirable effects occur in phase I studies, i.e. when an active ingredient is tested on healthy people for the first time?

That one finds some kind of reaction - that the blood pressure rises or falls, that a subject becomes dizzy or vomits, that happens again and again. And you would rather expect that from a healthy person than from a sick person who is already burdened by his illness. This is another reason why healthy test subjects are important in this phase. However, deaths or dramatic side effects such as in Rennes are the absolute exception.

What does that mean in concrete terms?

Specifically, this means: There has never been anything like this in Germany. And this despite the fact that the Federal Institute for Drugs and Medical Devices (BfArM) has approved 10,000 clinical trials over the past eleven years, including more than 2,700 with more than 100,000 healthy volunteers. Before the current case in Rennes, there was another case in Great Britain in 2006 in which life-threatening immune reactions occurred throughout Europe.

Subsequently, the guidelines for the first tests of active ingredients considered to be risky in humans were tightened. Nevertheless, a man has now died.

Since substances with a similar effect had already been tested without incidents, the active substance used in Rennes probably did not fall into this increased safety category. The active ingredient was also apparently well tolerated by participants who had tested lower doses in the previous months.

What else is being done to minimize risks?

For the first studies, the researchers are only allowed to use doses that are much lower than what will later be included in the drug. You start lower by powers of ten. Only if there are no problematic side effects would you administer higher doses and work your way up to the intended dosage.

It was the same in France, where cerebral hemorrhages only occurred in test subjects who took several doses of the active ingredient. But that means that this strategy does not offer complete security either.

No. There is no such thing as complete security. But a lot is being done to keep the risk as low as possible.

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