Before new drugs are approved, they must be tested with numerous patients. It will be examined whether they are effective and do not cause any problematic side effects compared to a previously approved drug or other treatment. The testing of new drugs takes place internationally. The pharmaceutical companies collaborate with clinics or medical practices in these studies – after all, patients should only be treated by medical doctors.
The physicians of these facilities ask eligible patients if they want to treat him as part of a study. Before a patient decides to participate, doctors must educate him about the planned treatment as well as treatment outside the study. If a patient decides to participate, this consent is recorded in a so-called “informed consent” document. However, patients can terminate their participation at any time without giving reasons (Read more here: Patients in clinical trials).
It is possible to initiate studies by companies or medical researchers at university hospitals and other academic institutions. By organizing and conducting a study, they can hire specialized service providers (so-called CROs – Contract Research Organization). However, the study will then remain the responsibility of the study initiator (the study sponsor), which can also be found in the entries in study registers.
Almost every study takes place in several medical institutions at the same time; and most of these facilities are located in several countries. Multinational studies are the norm, and 15 to 30 countries involved are not uncommon. As far as industry-initiated studies are concerned, medical facilities from the USA and Germany are particularly common (in the US, around 2,400 new industry-financed studies each year, around 600 in Germany). Clinics in neighboring European countries and Canada are also frequently involved; there are also other countries in several continents; because many countries have to be included,
to find enough willing patients with the disease in realistic time periods;
to meet the requirement of the regulatory authorities that the studies take into account a variety of ethnicities and lifestyles;
to meet the regulatory requirements of individual states, according to which the national approval of a drug is only possible if its testing takes place with the involvement of study centers of their own country. Germany does not think so, but Russia and India.
Most industry-initiated studies involving emerging-market clinics also have clinics in developed countries. So studies were not transferred to emerging markets, but only more emerging economies were and are included than they were ten or fifteen years ago.
Only uniform implementation makes studies usable for companies
Clinical trials are a prerequisite for authorities to decide on the approval of a drug (or the extension of its field of application). But they are also very expensive (cost two to three-digit million amounts). Firms are therefore very interested in each study being conducted in a way that provides meaningful data and is not rejected by regulatory agencies. Both requirements can only be fulfilled if patients are treated in accordance with international standards in all participating institutions. These include mandatory informed consent- ie the documented consent to participate after comprehensive information on the study and possible alternatives. It is necessary that patients are treated equally in all participating medical facilities. Otherwise, the data will not be usable and will not be recognized by the regulatory authorities.
These matters are governed anyway by provisions (such as the Good Clinical Practice of the International Conference on Harmonization, ICH-GCP). In addition, some companies have explicitly formulated it for themselves as a policy for international studies.
Unfortunately, there are institutions and service providers involved in studies that fail to comply with standards, even though authorities and companies counteract this by selecting procedures before the studies and controls during the studies. But such black sheep are not a phenomenon that only exists in emerging markets.
Motivations for study participation
The reasons for participating in a study in Germany are also good reasons for participating in India or another emerging market country. These include that study participants can usually be examined more thoroughly and cared for more closely than with routine treatments. These include the chance to possibly get a new treatment that helps well.
There are also good reasons for participating in studies for emerging medical institutions. Because even in these countries, there are quite a few clinics and medical practices on the level of industrial nations. They can and want to keep themselves up to date and contribute to the further development of medicine.
This is how a drug is invented and tested
Approval drugs – disease 1. Focus on Disease
The first step is the decision to launch a research and development program for a disease that has not yet been adequately treated.
Approval drugs – search 2. Target search
A target is determined in the course of the disease, i. H. a molecule in the body’s cells or in the blood on which a drug can start and thus influence the course of the disease favorably.
Medicines – starting substances 3. Searching for starting substances
Indications are sought as to what an active substance might look like. One way: screening. Here, up to 2 million substances are brought together with the target molecules. Those substances that have at least a weak effect on the target are called hits and examined more closely.
Approval medicines – tests 4. Through Chemical Optimization and Drug Candidate Testing
Optimization runs in several rounds. First of all, the hit substances are used to identify which structural features are required for an active substance. Molecules with such characteristics are synthesized by chemists and provided for testing. Test criteria include binding to the target, solubility, distribution, and degradation in the organism.
In later rounds, modifications of the molecules are made, with structural studies and computer simulations helping to select promising molecular changes. On the basis of the test results it is decided whether further chemical modifications are necessary or whether the prepared substance could be suitable as an active substance.
Approval medicines – examinations 5. Study of effects and tolerability
Once a promising substance has been synthesized, it must be tested for efficacy and safety with regard to toxicity and other potential adverse effects. In addition to cell cultures and animals are required. Substances that prove themselves are candidates for the drug.
Approval medicines – Phase 1 6. Studies with few healthy people: Phase I
Now the substance can be tested in humans. Healthy volunteers will examine how small amounts of the drug candidate behave in the body and at what level they begin to cause side effects.
Approval Medicines – Pharmaceutical form 7. Development of the dosage form
For the active substance, a dosage form is being developed, eg. As a tablet, capsule, ointment, solution for injection or emulsion, a suppository, an inhalable aerosol or an active ingredient patch.
Approval Medication – Phase 2 8. Studies with few patients: Phase II
For the first time, doctors use a drug containing the drug candidate in patients. Typically, 100 to 500 patients who volunteer will receive either the new drug or a comparative treatment. The doctors are investigating effectiveness, tolerability, and dosage.
Approval Medication – Phase 3 9. Studies with many patients: Phase III
Doctors in clinics in many countries are testing the drug with several thousand patients who volunteer. These receive either the new drug or a comparison treatment again. Efficacy, tolerability, and possible interactions with other medications are examined.
Approval Medicines – Assessment 10. Assessment by licensing authorities
Experts from the licensing authorities of many countries examine the submitted documents for all stages of development, for the production of the medicinal product and for the quality controls provided. If the effectiveness, safety, and quality of the drug are proven, they grant the approval.
Approval medication – further development 11. Application, observation, development
If the drug is approved, it can be prescribed. Doctors, manufacturers, and authorities pay attention to possible rare side effects. The leaflet will be updated regularly. If the drug is considered for other diseases, new clinical trials will be initiated.