What are clinical trials?
Clinical trials are conducted in order to investigate the safety and efficacy of new ways of treating, preventing, diagnosing and understanding human diseases. They also ensure that new therapies are better than existing ones. Nearly all treatments in use today began with clinical trials (i.e we wouldn’t even have aspirin if it weren’t for clinical trials). Ancora’s FAQ page has more information and a short video providing additional background on clinical trials if you would like to know more.
How many clinical trial phases are there?
Clinical trials usually consist of four to five different phases (0, 1, 2, 3, 4), each with a different purpose. A trial only moves to the next phase if the previous phase is successful based on pre-approved criteria. Each clinical trial has pros and cons and it is important you make an informed decision before enrolling in one.
What are pre-clinical studies?
Before starting a clinical trial, researchers conduct pre-clinical research where they test a potential new compound in cells or laboratory animals. These experiments ensure that a potential new medical compound displays the intended effects and is not toxic.
What is phase 0?: Does the drug reach its target in a human model?
Phase 0 (sometimes also called early phase 1) of a clinical trial is the first study conducted in humans. Investigators test a very small dose of medication in a very small number of volunteers (usually fewer than 15, typically healthy participants) for a short amount of time (between 7 and 14 days).
This phase is called an exploratory study, as it’s sole goal is to make sure the compound is not harmful to humans and that it behaves the same way researchers expect it according to their laboratory studies. Phase 0 studies aren’t widely used as they would not be helpful for all types of drugs and are not mandatory in the process of testing a new drug. However, conducting a small phase 0 study before moving to the other phases can help researchers save time and money by finding out immediately if the drug does not act as expected. The main difference between Phase 0 and other phases is that it is unlikely that the patients will benefit from the effect of the drug.
Phase 0 Pros:
- You help with the development of a drug that might benefit many people in the future.
- Due to the low drug dose, side effects are unlikely to occur.
Phase 0 Cons:
- The dose of the drug might be too small to benefit participants (if they are patients with the disease). The chances are little that volunteers will benefit from the effect of the drug.
- The study is often too short to show any therapeutic effect.
- You might have to do extra scans or give extra blood and biopsies to help researchers understand the effect of the drug on your body.
What is phase 1?: Is the drug safe and how does the drug interact with the human body?
The main goal of phase 1 clinical trials is to determine what dose of the drug can be given safely without provoking serious side effects. Additionally, researchers look for signs that the disease responds to the treatment. These studies usually include a low number (20 to 100) of healthy volunteers or people with the disease/condition and usually last several months to a year. The drug dosage is slowly increased for the clinical trial participants and side effects are closely evaluated.
Phase 1 Pros:
- These studies are usually conducted in major centers.
- These studies could be life-saving for those with life-threatening diseases.
- Patients are watched very closely by doctors who are tracking any side effects.
- These studies are usually non-randomized, meaning both the participants and the healthcare professionals involved know what medication is being tested.
- These studies are the most likely to offer financial compensation to the participants.
Phase 1 Cons:
- The potential side effects cannot always be predicted and can range from unpleasant to life-threatening.
- This is the phase with the most potential risk for patients because this is often the first study in which the drug is tested in humans.
- The main goal of these studies is not to find out if the drug works against a specific disease, but rather to demonstrate safety.
⇒ Approximately 70% of drugs in phase 1 move to phase 2
What is phase 2?: What are the side effects and which dosage works the best?
Once a dose or range of doses of a new medication has been determined to be reasonably safe in phase 1, a phase 2 clinical trial can then be initiated in order to test the efficacy of the treatment. Depending on the type of treatment, doctors might look at a different type of benefit or response. For example, they could look at whether cancer shrinks or disappears, or if there is a longer period of time before cancer comes back. Sometimes, quality of life is also evaluated. Often it is determined if the medication allows patients to live longer than they would have without the test medication.
Usually, phase 2 studies recruit between 25 and 300 patients who are suffering from the same type of illness and the studies last for about 2 years.
Sometimes, participants are divided into groups and receive different treatments or doses of medication. Being able to compare different treatment groups helps researchers determine which treatment protocol provides the best balance of safety and efficacy.
Example #1:
- Group 1 receives the standard treatment for their condition, also called “standard of care” treatment.
- Group 2 receives the standard of care treatment, plus the new treatment that is being studied.
Example #2:
- All the groups receive the same treatment but at different doses.
In some trials, one group receives a placebo (a pill without therapeutic value), but for ethical reasons, this is usually not the case in cancer studies or clinical trials for serious conditions.
Phase 2 Pros:
- You get the chance to try out very innovative treatments that are not yet on the market and at a dose that has already been pre-evaluated as being safe.
- You will be closely watched out during the study and doctors and other healthcare professionals will monitor your health, well-being and the state of your condition.
Phase 2 Cons:
- Phase 2 studies are usually where unsuccessful treatments are identified, either due to lack of efficacy or safety.
- As a volunteer, you will not be able to decide which group you would like to be in. Randomization will be used to assign participants to the treatment groups, to help keep the clinical trial results as neutral as possible.
- Even though the treatment has already been tested in the previous phases, you may still have side effects that the doctors are not expecting.
⇒ Approximately 33% of drugs in phase 2 move to phase 3
What is phase 3?: Is the new treatment better than the standard of care treatment ?
If a treatment has been shown to work without harmful side effects in a phase 2 study, it will be further tested in a phase 3 clinical trial before it can be approved for general use and sold on the market. The purpose of phase 3 studies is to evaluate how well a new treatment works. Participants are usually randomized and either get the new treatment or the standard of care. Both patients and doctors are usually blinded, meaning none of them will know which treatment each participant is receiving. This reduces bias in the study.
Phase 3 studies are larger and involve up to 3,000 people who are suffering from the condition that the new medication is meant to treat. These phase 3 clinical trials can last for several years.
Phase 3 Pros:
- You might have access to the latest innovative medication, which in some cases could be life-saving.
- These studies are usually done in many locations around the globe at the same time so you may not have to travel far.
Phase 3 Cons:
- Phase 3 studies usually last several years. The time each single participant needs to remain in a phase 3 clinical trial varies from case to case. However, participants should be aware that they might need to commit to the long-term. Of course, it is always possible to drop out of the study at any time and for any reason.
- Some side effects that only appear over time and might not have been detected in the previous phases might be discovered.
⇒ Approximately 25 to 30% of drugs in phase 3 move to phase 4
Submission of a New Drug Application (NDA) to the FDA: is the new drug safe and effective enough to be approved for sale and marketing?
When phase 3 clinical trials (or sometimes phase 2 trials) demonstrate that a new therapy works well, the drug sponsor submits a new drug application (NDA) to the Food and Drug Administration (FDA).
The NDA is a comprehensive document that includes evidence that the new treatment is effective for its intended use, safe, and that its benefits outweigh its risks. After the FDA has accepted the NDA, it has 10 months (six months for priority drugs) to make a decision on whether to approve the new drug for treatment in its proposed use(s) in humans.
If approved, the drug is labeled as standard of care and can be sold and marketed in the United States.
What is phase 4?: What is the long-term data for a treatment and how can it best be used?
Even after being approved by the FDA, new drugs are closely watched over for a long period of time in phase 4 studies, which are also known as postmarketing surveillance trials. This phase involves thousands of participants and can last for many years. The aim is to get a full picture of a new drug’s safety, efficacy, benefits or optimal use as it can evolve with time as more diverse types of people are prescribed the treatment.
Phase 4 Pros:
- You will be taking a treatment that is already fairly well understood and approved for use.
- You will be monitored over a longer period of time.
- The effects of the drug are studied in a more diverse population than in the previous phases, where only carefully selected participants fitting certain eligibility criteria are enrolled.
- Usually Phase 4 trials are not blinded, so you might be able to find out which treatment you are receiving (called an open-label study).
Phase 4 Cons:
- Rare or long-term adverse side effects or new safety concerns might be discovered.
- As the drug is already approved, you can access it outside of a clinical trial, which might be more convenient.
If you would like to learn even more about clinical trials make sure to visit Ancora's Resources section which includes an FAQ page and Glossary. If you would like to search for trials, make sure to check out Ancora’s Trial Search tool.