Good medical practices and having sound medical cures are probably the only things that everyone can agree on. More than crime, education, civil rights, is the interest that good medical practices should be available. There are many types of medical programs and research projects underway. But one that is very important to the society at large is the issue of the Food and Drug Administration (FDA) drug approval process. How does that process work and how do the drug companies work with the FDA to take a drug to market?

The Purpose of Clinical Research

All new drugs need proof that they are effective, as well as safe, before they can be approved for marketing. It's important to realize, however, that no drug is absolutely safe. There is always some risk of an adverse reaction. But the FDA uses a cost benefit analysis to determine if the drug can be released to the public. The FDA determines that when the benefits outweigh the risks the FDA considers a drug safe enough to approve. So the purpose of clinical research is to determine the safety and efficacy of the Investigational New Drug (IND) for the treatment of a particular disease or condition in humans. Clinical research is divided into three phases in the normal course of testing.

The Research Phases

Before a drug can be approved for sale to the public there is a set of clinical tests that must be performed. There is the Pre-Clinical Research Stage. Here the drug is synthesized and purified. Animal tests are performed, and institutional review boards assess the studies and make recommendations on how to proceed. If the recommendations are positive, then an application to the FDA occurs and clinical tests begin.

Phase 1: clinical studies in this phase represent the first time that an IND is tested on humans either healthy volunteers or sometimes patients. The purpose of these studies is study in a clinical setting the metabolism, structure-reactivity relationships, mechanism of action, and side effects of the drug in humans. If possible, phase 1 studies are used to determine how effective the drug is. Phase 1 studies are usually conducted on 20 to 80 subjects.

The purpose of phase 2 clinical trials is to determine the efficacy of a drug to treat patients with a specific disease or condition, as well as learn about common short-term side effects or risks. These studies are conducted on a larger scale than phase 1 studies and typically involve several hundred patients.

Phase 3 clinical trials provide more information about the effects and safety of the drug and they allow scientists to extrapolate the results of clinical studies to the general population. Phase 3 studies generally involve several hundred to several thousand people.

There are several checks and balances in the process of clinical trials; among them is the use of institutional review boards (IRBs) and advisory committees. IRBs are designed to protect the rights and welfare of people participating in clinical trials both before and during the trials. IRB's are made up of a group of at least five experts and lay people with diverse backgrounds to provide a complete review of clinical proceedings. The CDER uses advisory committees of various experts in order to obtain outside opinions and advice about a new drug. It also provides new information for a previously approved drug, as well as labeling information about a drug, guidelines for developing particular kinds of drugs, or data showing the adequate safety and effects of the drug.

The Application Process

The sponsor of a drug makes a formal application to the FDA to approve a new drug for use in the United States by submitting a new drug application (NDA). The NDA must include results and analyses from tests of the drug on both animals and humans, as well as a description of how the drug was manufactured. The NDA must provide enough detailed information for FDA reviewers to make several critical decisions. The result of the study must show whether the drug is safe and effective and whether its benefits outweigh its risks. It also decides whether the drug's labeling information is appropriate, and whether the manufacturing methods used to obtain the drug are adequate for ensuring the purity and integrity of the drug.

The process of developing and testing a new drug is a lengthy one. The FDA estimates that it takes a little over 8 years to test a drug, including early laboratory and animal testing, before there is final approval for use by the general public. Various efforts, however, are underway to reduce the approval time.

Promising Experimental Drugs

Eight years is a long time to review a drug. Some patients, especially terminally ill patients, don't particularly care if the drug meets high standards of safety. They don't have the time. Taking any drug, in their view, is better than the alternative. So today's policies also allow some investigational drugs even before they are approved for marketing.

These new policies called "expanded access" protocols include the Treatment Investigational New Drug (IND) application and the parallel track mechanism. Both tracks allow promising drugs, not yet approved for marketing, to be used in moderately unrestricted studies where the intent is not only to learn more about the drug, especially about its safety, but also to provide treatment for people with no real alternative. But these expanded access protocols still require clinical researchers to formally investigate the drug in well-controlled studies and to supply some evidence that the drug is likely to be helpful.

Final Actions

The FDA's decision whether to approve a new drug for marketing comes down to answering two questions:

1. Do the results of well-controlled studies provide substantial evidence of its effectiveness?

2. Do the results show that the product is safe under the explicit conditions of use in the proposed labeling? Here "safe" is a relative term; it means that the benefits of the drug appear to outweigh its risks.

When the review is complete, the FDA writes to the applicant to say the drug is either approved for marketing, is "approvable," provided minor changes are made, or is not approvable because of major problems. In the last case, the applicant can then amend or withdraw the NDA or ask for a hearing. Once its NDA is approved, a drug is on the market as soon as the firm gets its production and distribution systems going.