Dr. Stephan de la Motte: Research in humans is no airbag and the participant is no dummy

Why are clinical trials necessary in medical research?

Contract research
Contract medical research, which is not to be confounded with market research, is a young branch of trade, which did not even exist some 30 years ago and which, over the past two decades, has evolved from a handful of isolated “one-man bands” into a global industry, whose biggest company employs up to 40,000 people worldwide. How did that happen?

What determines the value of a drug?
Many diseases cannot be treated at all or only with unsatisfactory results. Some of the currently available drugs, though effective, have undesired side effects. In addition, new diseases may emerge from time to time or may be identified as such. Therefore, new or better med­­icines would be of advantage to many patients.

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Medicines are different from other prod­­ucts in one significant respect. It is not the product itself that counts – the tab­­let, the spray, the ampoule and so on – but solely the information that comes with it: the instructions for use, the dos­­ing guidelines, the warnings, the contraindications. In the end, this informa­tion will be crucial in determining to which degree the product is actually useful or dangerous.
Most products can be tested by the buy­­ers themselves before actually using them. Take a car, for example: One test drive will reveal if the brakes, steering, lights et cetera work properly. As a last resort, you could even take a car off the assembly line and drive it into a wall in a crash test to check the stability of the passenger compartment and the actual functionality of the airbag – an expensive option, sure, but it would be possible to do it.

Just try and see?
Seriously ill people need the drug im­­me­­diately. Can they take the new tablet, con­­taining the new substance, even if they don’t know if the dosage is right? If the dosage is too low, the drug will not be effective and the disease will have time to cause permanent damage; in the worst case, the patient may die of the disease. If the dosage is too high, the patient may die of an overdose. And is this drug really appropriate for treating this condition?
To “just try and see” is not acceptable from an ethical point of view. To make sure the use of the medicine is beneficial and safe, the complete and accurate information must be available before administering it to a patient – if the in­­formation comes later, it is too late.

What type of information is needed?
To be able to decide whether a new drug is predominantly useful or predominantly harmful, it is essential to achieve a large amount of scientific knowledge. In many cases, it is not the medicine as such that may either cause harm or have a positive effect, but it is the way it is administered or other circumstances of the therapy, such as the dosage, interactions with other medications the pa­­tient is taking or the impact it has on other, concurrent diseases, et cetera.

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Information on possible undesired ef­­fects of drugs (commonly referred to as side effects) are particularly important. If the side effects are known, the doctor can keep an eye on them, recognize them in time and stop the treatment before permanent damage occurs.

Equally important is the information about conditions in which a particular substance must not be used at all (known as contraindications) because it is clear from the outset that in these particular cases the potential for damage is greater than the potential benefit.

Humans are highly complex organisms. Huge differences between people with regard to nutrition, lifestyle, work environment, local climate and other conditions may further increase the complexity of diseases and their treatment options.

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The best solution: clinical trials
Proper clinical trials are thus indispensable to enable a conclusive evaluation of the usefulness of new or improved drugs. Only in adequately controlled and monitored clinical trials is it possible to gather reliable data and findings, which can then be used as a basis to derive generally valid recommendations for use.

In recent years, significantly higher in­­ternational scientific standards have been implemented. The demands on the ev­­idence of effectiveness as well as on the evidence of the absence of adverse effects have increased significantly.

Previously, one single study was sometimes considered sufficient, while to­­day, it is not uncommon to conduct up to 30 clinical trials on humans to obtain the international approval for a single nov­­el medicine. Only in very rare cases, if, for example, the relevant substance is expected to be effective against a hitherto untreatable disease, would the re­­quirements be relaxed.

Specialist contract research institutes
The general trend towards specialization has not spared the phenomenon of “clin­­ical trials”. The proper conduct of clini­cal trials in humans is regulated by many international guidelines and national laws, which means that even the mere execution of such trials requires a large amount of expert knowledge, irrespective of the particular field of medical expertise.
The pharmaceutical industry alone is no longer able to execute such a high amount of medical trials from its own resources. This is why the pharma and biotech in­­dustry increasingly relies on professional contract research institutes which have specialized in conducting clinical trials in compliance with international standards.

1After completion of the medical education as physician and the doctoral thesis in neurophysiology, Dr. de la Motte worked as a staff surgeon at the Ger­­man Bun­­deswehr, at a pharmacology/toxicology laboratory and in a hospital as anaesthet­­ist. He has worked for Harrison Clinical Research for 15 years. He ist Chief Medical Officer at Harrison Clinical Re­­search.