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New drugs are tested in people through clinical trials. The clinical trial process is well documented; some excellent resources are:

Why Consider a Clinical Trial?

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The data (information) from clinical trials is analyzed to answer the question: "Is this drug relatively safe and effective for treatment of a specific condition?"

To understand clinical trial results, and claims made about clinical data or drug performance, it is very helpful to have a basic understanding of how statistics are used to evaluate these types of important issues. MedPage Today has assembled a useful introduction to biostatistics that can be a helpful starting point: MedPage Today Guide to Biostatistics

FDA-approved cancer drugs that are on the market have been tested in clinical trials and shown to be effective - although they do not work for all patients in all cases. Extensive information exists about how to dose and combine these drugs, along with information about what side effects might occur, and how to treat them.

In short, approved drugs are generally the first treatment options offered patients. For patients who are failed by, or cannot tolerate approved therapies, clinical trials may offer another treatment option.

Example: a newly diagnosed lung cancer patient will typically receive chemotherapy that oncologists have tested and agree is likely to have the strongest effect on the patient's lung cancer (e.g., several regimens of cisplatin and paclitaxel (Taxol) or carboplatin and paclitaxel).

If his cancer continues to progress or has returned in spite of that treatment, the patient may begin to search for new drugs - drugs in development that are not yet approved. During the search, the patient will find trials of new drugs and consider entering some of them. It needs to be emphasized that the best and easiest way to get access to an unapproved drug in a clinical trial.

Exception: Trials determining the first-line treatment options used by patients require testing in newly-diagnosed patients.

Example: the first-line treatment option for most colorectal cancer patients has evolved over the years, from being 5-fluorouracil (5-FU) with levamisol, to 5-FU with leucovorin, to 5-FU with leucovorin and irinotecan. In 2001, a combination of 5-FU with leucovorin and oxaliplatin was compared to 5-FU, leucovorin and irinotecan. Patients testing the therapies for first-line status were newly-diagnosed.

The NCI and NLM resources (above) provide extensive information about clinical trials, including questions that patients can consider when evaluating how a trial could help them.

Clinical Trial Entry Criteria

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Clinical trials generate data (information) used by the FDA to determine if a drug should be approved. In order to reduce the number of variables in the data and allow meaningful analysis of safety and activity data, patients in the trial must be similar in profile.

Example: Drug X is being tested against breast cancer. Prior research has shown that Drug X can cause liver failure in people with bad liver function, resulting in death. If clinical trials of Drug X include patients with bad liver function, many trial participants may die as a result of their liver problems. These deaths may hide Drug X's effectiveness against breast cancer.

To make certain that each patient fits that profile the clinical trial will establish criteria for patient entry into the trial. Clinical trial entry criteria are specific to each trial. Some common examples of clinical trial entry criteria are:

  • Age range between 18 and 75
  • No previous chemotherapy
  • Stage 3 lung cancer
  • No difficulty breathing
  • Good liver function

Because of these entry criteria, some patients may not be eligible to enter the clinical trial. Or, perhaps the patient is eligible but lives too far away from the clinical trial site to participate in the trial.

It is at this point — when a patient has advanced disease and no approved treatment options, and is unable to enter an appropriate clinical trial — that a patient may think about trying to get the new, unapproved drug outside of the clinical trial.

This access to an unapproved drug outside of a clinical trial has many names but is most commonly referred to as compassionate use.

Pre-clinical Studies

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Before a new medicine is tested on people (which is what the "clinical" part of the phrase "clinical trial" refers to), researchers must first determine its physical and chemical properties in the lab and study its effects on laboratory animals.

Phase I Trials

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Information on the new drug is submitted to the FDA (Food and Drug Administration) in an application known as an IND. IND stands for Investigational New Drug.

First the FDA reviews the drug company's clinical trial design to be certain that it is scientifically sound and ethical. Once FDA agrees that the clinical trial can proceed, the drug company must then get permission form the local clinical trial site. The local clinical trial review is conducted by the IRB or institutional review board.

When the IRB agrees that the trial can proceed, a small number of patients is given the drug by the clinical trial physicians, known as clinical investigators — they are the scientists who run the clinical trials. During a Phase I trial, the scientists try to learn what happens to the drug in the human body, such as how it affects various organs, how it's metabolized and the dose that can be safely given. Usually a very small number of people are involved in this first phase of human testing.

Phase II Trials

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During Phase II testing a larger number of patients are recruited to the clinical trial. The goal of a Phase II trial is to learn whether the dose that has been found to be safe in Phase I is effective against the disease being treated. In some cases, the results are so impressive a drug can be approved on the basis of Phase II trials alone. More often, the drug moves into Phase III testing.

Phase III Trials

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Phase III trials are designed to learn if the safety and effectiveness results from the Phase I and II clinical trials will be sustained when the drug is studied in a much larger population. Phase III studies enroll hundreds and sometimes thousands of patients. As an added benefit, testing the drug in a large population is more likely to reveal less common side effects and provide longer-term safety data. The Phase III trial usually compares the new drug's activity to the current treatment for a disease. In order for the new drug to get FDA approval, it only needs to demonstrate that it is not inferior to the current treatment.

Post-marketing Studies (Phase IV Trials)

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If a drug company has received accelerated approval for a drug, the drug company must confirm in a Phase IV clinical trial that the early results they found — such as tumor shrinkage — actually mean that the patient lives longer than if they did not take the new drug.