Medical progress is made possible mainly due to research. This also means that new medications need to undergo tests on humans before being released onto the market. What are those who allow themselves to serve as test humans letting themselves in for exactly? How are they protected?

“Phew!” moans Matthias who, along with his mother, has just combed through ae two-paged consent form. He has had diabetes for two years, and his doctor has asked him if he would like to take part in a study. The study is to examine different lancets.

A new technique has been developed that is supposed to reduce the pain of one particular type of lancet vs. another. The fact that the pain on finger pricking during monitoring is the one thing that really annoys Matthias, he is interested in taking part. He signs the form, and his mother does the same. The study sister then comes in and brings him to a large box with two holes.

Matthias has to put his hands through, and the testing begins. Although he can’t see which device the sister is using, he can certainly feel it. He hardly feels the first prick. He gives it a mere one on the pain scale. The second one, however, is heftier, and Matthias only gives it a five.   

A child as guinea pig?
Medical progress would not be possible without clinical studies. Especially in paediatric diabetology, many promising new developments are in the test phase that should serve to improve treatment: these range from pen needles to lancets, from insulin pumps with new functions to new types of insulin with faster or slower, more steady modes of action.

Such studies can only be carried out if patients are willing to take part in them. In paediatric diabetology, however, the whole family is automatically involved. How willing is one to be a guinea pig? Information on the background of clinical studies can help one make that decision.    

Studies are well supervised
The law ensures the safety of study subjects with a strict set of procedures that need to be followed. The safety of the participant always takes first priority. The study protocol needs to be submitted to an ethics committee. The ethics commission will probably refer to the World Medical Association's Declaration of Helsinki, 1975, which states that the protection of participants from any possible long-term effects must be ensured.

Members of ethics committees usually consist of physicians, natural scientists, lawyers, and theologians. The ethics commission votes for or against the continuation of the programme, and offer advice to the study leaders on how best to inform the patients thoroughly on the study procedure.

If the study involves children, this information will also be presented to the parents or guardians. Should problems arise during the study, or should the medication not be behaving like it should, a decision will be made by the study leader, or the ethics commission, to cease operations.   

Various study principles
Imagine that a new type of insulin is being developed which, under certain circumstances, is supposed to act faster than the other types. Normally, any new substance will be compared to a placebo, i.e., a substance with no active ingredients. This particular approach is known as ‘placebo controlled’. This approach, of course, cannot be carried out on people with diabetes. This is why any new insulin will be tested against one of the best ones already on the market.

The subjects are divided into the two groups at random. This procedure is called ‘randomization’. In order to be able test the action of a particular type of insulin objectively, neither the doctor nor the patient should know which insulin is being used. This is called the ‘double blind’ principle.

In Matthias’s lancet study, for instance, Matthias cannot see the pricking, so he doesn’t know which lancet is being used, or even if he is being pricked by a real lancet (‘single blind’). Prior to commencement, a statistical calculation will predict why the new substance or procedure may or may not succeed, and how many participants will be required.

Not everybody can take part
Not everybody can take part in a study. Often, certain pre-study criteria must be met on factors such as age, gender, duration of diabetes, and state of general health. These factors will be thoroughly tested at outset. Before child and parent are able to agree to participate, an informative discussion will take place on exactly why the study is being carried out. Children will be offered this information in a language appropriate to their age. Once agreement has been reached by the parent/guardian and child, they can start.
 
The long road to approval
The development phase of a new medication such as insulin takes a considerable amount of time. It can take years, even decades, until a pharmaceutical company is given approval from the authorities to release something onto the market. Before this can take place, the substance must undergo certain study phases.

Phase 1 is carried out on healthy individuals to test the general tolerance of the substance, how it is dispersed in the body, and how well it is secreted. The participants, of course, receive a glucose solution intravenously in order to prevent hypoglycaemia.

Phase 2 involves those suffering from diabetes. Here the new substance is tested on the participants to see if it works, and to make sure that the side effects remain within acceptable limits.

Having completed phase 1 and phase 2 successfully, phase 3 can then be carried out, which involves a much larger chunk of population, whereby the dosage and method of administration are finalized.

After all the results from the phase 3 are collated and it is clear that the new substance is effective and safe, it is presented to the Germany’s Federal Institute for Drugs and Medical Devices (BfArM), or the European Medicines Agency (EMEA) for approval. Once this is granted, every patient can be given the new insulin.

Phase 4 examines whether the new substance holds it own in the general populace—whether the risk:benefit ratio remains positive for the users. Phase 4 is also used to detect and describe any rare side effects that may appear.            

What’s in it for the participants?
In paediatric diabetology, there can be no progress without the help of families. Their participation in trials serves as a huge contribution. There are also specific perks for the participants that make up for their trouble. Each step is supervised very closely, and the examinations at outset and during the study are much more detailed and thorough than those which are done for non-participants.

In addition, documentation is done much more closely during the study, increasing the level of attention the participant receives. Experience shows that the outcomes of those participating in studies are generally better than those on normal treatment—independent of whether the participant uses the test substance or not.

Of course, the participant can withdraw at any time from the study. One does not have to give a reason, and doesn’t have to fear being disadvantaged because of it. Participation in a study does not pose any additional cost. If one uses special medications or devices, it is all covered by the public health insurance.     

Research through progress
One of the greatest breakthroughs in the history of medicine was the discovery of insulin, which occurred just on 90 years ago. This ushered in the era of insulin treatment for diabetes, a disease which had, until then, often posed a death sentence for those unlucky enough to have acquired it. Nevertheless, paediatric diabetes teams, along with their patients, are obligated to administer the best possible treatment for their patients, based on the latest scientific findings and clinical trials until a cure is found.

As for Matthias, he had fun participating in the study. He really believes that this new lancet is much less painful. He and his mother are eager to know if the other participants also found this to be the case, so that the advantage of the new lancet can be scientifically confirmed.  

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Prof. Thomas Danne, MD
Paediatric Diabetologist
Kinderkrankenhaus auf der Bult,
Hanover
E-Mail: danne(at)hka(dot)de