Question

Clinical trials are usually conducted in phases that build on one another. Each phase is designed to answer certain questions. Knowing the phase of the clinical trial is important because it can give you some idea about how much is known about the treatment being studied. There are pros and cons to taking part in each phase of a clinical trial.

Phase I clinical trials: Is the treatment safe?

Phase I studies of a new drug are usually the first that involve people. The main reason for doing phase I studies is to find the highest dose of the new treatment that can be given safely without serious side effects. Although the treatment has been tested in lab and animal studies, the side effects in people can’t always be predicted. These studies also help to decide on the best way to give the new treatment.

Key points of phase I clinical trials:

• The first few people in the study often get a very low dose of the treatment and are watched very closely. If there are only minor side effects, the next few participants may get a higher dose. This process continues until doctors find a dose that’s most likely to work while having an acceptable level of side effects.
• The focus in phase I is looking at what the drug does to the body and what the body does with the drug.
• Safety is the main concern at this point. Doctors keep a close eye on the people and watch for any serious side effects. Because of the small numbers of people in phase I studies, rare side effects may not be seen until later.
• Placebos (sham or inactive treatments) are not part of phase I trials.
• These studies usually include a small number of people (typically up to a few dozen).
• Often, people with different types of cancer can take part in the same phase I study.
• These studies are usually done in major cancer centers.
• These studies are not designed to find out if the new treatment works against cancer.

Overall, phase I trials are the ones with the most potential risk. But phase I studies do help some patients. For those with life-threatening illnesses, weighing the potential risks and benefits carefully is key.

Phase II clinical trials: Does the treatment work?

If a new treatment is found to be reasonably safe in phase I clinical trials, it can then be tested in a phase II clinical trial to find out if it works. The type of benefit or response the doctors look for depends on the goal of the treatment. It may mean the cancer shrinks or disappears. Or it might mean there’s an extended period of time where the cancer doesn’t get any bigger, or there’s a longer time before the cancer comes back. In some studies, the benefit may be an improved quality of life. Many studies look to see if people getting the new treatment live longer than they would have been expected to without the treatment.

Key points of phase II clinical trials:

• Usually, a group of 25 to 100 patients with the same type of cancer get the new treatment in a phase II study. They’re treated using the dose and method found to be the safest and most effective in phase I studies.
• In a phase II clinical trial, all the volunteers usually get the same dose. But some phase II studies randomly assign participants to different treatment groups (much like what’s done in phase III trials). These groups may get different doses or get the treatment in different ways to see which provides the best balance of safety and effectiveness.
• No placebo (sham or inactive treatments) is used.
• Phase II studies are often done at major cancer centers, but may also be done in community hospitals or even doctors’ offices.

Larger numbers of patients get the treatment in phase II studies, so there’s a better chance that less common side effects may be seen. If enough patients benefit from the treatment, and the side effects aren’t too bad, the treatment is allowed to go on to a phase III clinical trial. Along with watching for responses, the research team keeps looking for any side effects.

Phase III clinical trials: Is it better than what’s already available?

Treatments that have been shown to work in phase II studies usually must succeed in one more phase of testing before they’re approved for general use. Phase III clinical trials compare the safety and effectiveness of the new treatment against the current standard treatment.

Because doctors do not yet know which treatment is better, study participants are often picked at random (called randomized) to get either the standard treatment or the new treatment. When possible, neither the doctor nor the patient knows which of the treatments the patient is getting. This type of study is called a double-blind study. Randomization and blinding are discussed in more detail later.

Key points of phase III clinical trials:

• Most phase III clinical trials have a large number of patients, at least several hundred.
• These studies are often done in many places across the country (or even around the world) at the same time.
• Phase III clinical trials are more likely to be offered by community-based oncologists.
• These studies tend to last longer than phase I and II studies.
• Placebos may be used in some phase III studies, but they’re never used alone if there’s a treatment available that works.

As with other studies, patients in phase III clinical trials are watched closely for side effects, and treatment is stopped if they’re too bad.

Submission for FDA approval: New drug application (NDA)

In the United States, when phase III clinical trials (or sometimes phase II studies) show a new drug is more effective and/or safer than the current standard treatment, a new drug application (NDA) is submitted to the Food and Drug Administration (FDA) for approval. The FDA then reviews the results from the clinical trials and other relevant information.

Based on the review, the FDA decides whether to approve the treatment for use in patients with the type of illness the drug was tested on. If approved, the new treatment often becomes a standard of care, and newer drugs must often be tested against it before being approved.

If the FDA feels that more evidence is needed to show that the new treatment's benefits outweigh its risks, it may ask for more information or even require that more studies be done.

Phase IV clinical trials: What else do we need to know?

Drugs approved by the FDA are often watched over a long period of time in phase IV studies. Even after testing a new medicine on thousands of people, the full effects of the treatment may not be known. Some questions may still need to be answered. For example, a drug may get FDA approval because it was shown to reduce the risk of cancer coming back after treatment. But does this mean that those who get it are more likely to live longer? Are there rare side effects that haven’t been seen yet, or side effects that only show up after a person has taken the drug for a long time? These types of questions may take many more years to answer, and are often addressed in phase IV clinical trials.

Key points of phase IV clinical trials:

• Phase IV studies look at drugs that have already been approved by the FDA. The drugs are available for doctors to prescribe for patients, but phase IV studies might still be needed to answer important questions.
• These studies may involve thousands of people.
• This is typically the safest type of clinical trial because the treatment has already been studied a lot and might have already been used in many people. Phase IV studies look at safety over time.
• These studies may also look at other aspects of the treatment, such as quality of life or cost effectiveness.

Question

How would you change the current pathways to FDA approval (Phase I-IV) studies to make the process more efficient and faster?

500 words no plagiarism no bullet points please

Answer 1

Ans-"The Society encourages FDA to offer more detailed guidance on the specific types of patient information that would be useful to the agency in its product reviews. Increasingly, patients are faced with the challenge of ensuring that they are providing the type of information that will be useful to researchers, product developers, and regulators. Furthermore, in open forums with limited time, such as PFDD meetings, it is critical to be able to deliver this information in an efficient and effective way."

FDA should also increase transparency regarding how patient information is being reviewed internally and incorporated into the agency’s decision-making process." … "Additionally, there is a lack of clarity as to how these reports will be updated in the future as new information about the diseases becomes available or if treatment regimens change."

National Kidney Foundation

"Develop public guidance on opportunities for patient engagement, tools and processes that will be used for engaging patients, topic areas where patient perspective will be collected, and specifics on how patient perspectives are incorporated into FDA decisions."

The Leukemia & Lymphoma Society

"LLS recommends that the FDA establish a transparent process to work with industry and the patient community to develop template frameworks for [Patient-Reported Outcomes] PROs to streamline the inclusion of substantive, useful PRO data within clinical trials intended to support an approval or new labeling claim. These templates should include best practices for survey content and systematic data collection methods which are tailored for specific disease areas and other variations."