8. Phase II Clinical Studies - Proof of Concept

Step 8. Phase II Clinical Studies - Proof of Concept

Trials in patients. Once the volunteer trial results have shown that it is safe to proceed, the next step is to start clinical trials in patients with the disease that is being treated. The same guidelines and regulations apply.

In Phase II and later Phase III clinical trials, there are usually two treatment groups. One group has the active medicine and one group has a dummy medicine which has no effect on the body (called a ‘placebo’) or a comparator medicine (usually the ‘gold standard’ therapy for the disease in question). These studies are usually run as ‘double-blind’, ‘randomised’ trials.

• ‘Double-blind’ means that both the doctor and the participant do not know who is receiving the active medicine or placebo or comparator.
• ‘Randomised’ means that the treatment groups are chosen by chance. This is usually done with a computer that generates a random code. It cannot be influenced by the doctor or anyone else.
• ‘Placebo-controlled’ means that some participants will receive a placebo given under the exact same conditions as the active medicine. This allows the effects related to the medicine to be separated. For example, if a participant in a trial complains of a headache it is important to know if that is related to the active medicine. If the same number of participants receiving placebo complain of headaches, this shows that the headache is unlikely to be due only to the active medicine.

All the details of the trial are described in the Study Protocol and the information is collected in the Case Record Form. The results will be analysed using statistical tests.

These trials are usually carried out in 100 to 500 patients. They are designed to obtain information about the effect of the medicine on the actual disease (‘proof of principle’). This is also the stage when different doses of the medicine are used to find out which is the best dose. This dose is then used for the next phase of larger clinical trials (Phase III).

The more that can be learned about the effect in the patients at this stage, the easier it is to decide if the development should continue. However, Phase II studies are too small to be able to provide sufficient evidence about efficacy and safety. Therefore, building up more and more information about how the medicine works in patients reduces the risk of failing at the next stage (Phase III or Development for Launch), which is the most complicated and most expensive phase of development.

Since these Phase II trials are carried out in patients, the studies are usually run in several hospital sites by hospital doctors, opposite to the Phase I performed in special units.

Conducting trials in several different sites at the same time is more complicated than conducting a trial in a single site:

• All the investigators and study nurses have to be trained using an established protocol that is conducted the same way in all the sites.
• The medicine has to be exported to different countries and stored properly in the different pharmacies.
• The blood samples collected from patients in the clinical trial are usually sent to a single central laboratory.
• All local country rules and regulations have to be understood and followed.
• Ethics Committee opinion and NCA approval is usually required in each country.

All of this has to be coordinated by the global study team.

Summary: By the end of the Phase II studies, the programme will have:

• taken 8.5 years, on average
• cost €1 billion, on average.

Of 10 medicines that were tested in Phase I and Phase II, on average only 2 will continue to the next phase.