Breakthrough?: Understanding the Drug Development and Testing Process

Everyone is gratified by news of a major drug breakthrough, especially if it promises help for people who are terminally ill or severely disabled. And if you or a loved one has been praying for such a drug, the news may seem like a miracle. Unfortunately all too often, reports in the press are exaggerated or seriously inaccurate interpretations of scientific findings. Really significant advances happen less often that the popular press (newspapers, the Internet, radio, television, and magazines) would have us believe.

A healthy skepticism coupled with a working knowledge of the scientific process for drug discovery can help you assess news reports and professional scientific journals. When hearing of advances in treatment for a particular condition or disease, it is helpful to ask the following questions and use the following guidelines:

• Where did the news report appear? Many newspapers, magazines and broadcasters assign specialized reporters to cover health and medical affairs. Some publications and broadcasts emphasize sensational stories. Do you trust the news source and the reporter?
• Is it too good to be true? News stories that report complete cures and Internet marketers that offer miracle treatments are likely to be wrong. Many diseases such as Alzheimer’s Disease, Parkinson’s Disease and AIDS are very complex and poorly understood. Years of study into the basic science seem to show us how much we have to learn. We will have more partial successes and more failures before effective treatments are found.
• What is being reported? The results of one study in a small number of patients rarely, if ever, will be conclusive. At best it shows a promising avenue for future research (which may or may not be safe and effective). Many times these results will be discussed in scientific journals or conferences, and news reporters will jump to conclusions.
• What does your doctor think? Ask your healthcare provider what he or she knows about the news story. While doctors and other practitioners don’t know everything, there is a good probability that they would know about a truly important medical advance. If possible, bring the actual report with you to help your health care provider to assess the information that you found.
• Has the research been reviewed by scientists and other qualified professionals? The most authoritative scientific studies are published in peer-reviewed medical journals. They have been read and critiqued by highly regarded professionals. Websites rarely have a quality assurance process, so be particularly aware of websites that do not have information about who writes their articles and where they get the source material.

The Drug Development and Approval Process

Controlled clinical trials, in which results observed in patients getting the drug are compared to the results observed in patients receiving a different treatment, are the best way science has come up with to determine what a new drug really does. Controlled clinical trials are a legal requirement that the U.S. Food and Drug Administration (FDA) makes drug makers prove that the new treatments are both safe and effective.

The process starts with the drug developer (usually a pharmaceutical research and development company), who is seeking to develop a useful and profitable drug. The researchers analyze the drug’s chemical properties and test it in animals to determine any toxic reactions. The way that drugs react in animals is not always the same as they will behave in humans. Further tests are necessary before accurate conclusions can be drawn about the effect of drugs in humans.

They developer then asks the FDA for permission to test the drug in people. A panel of scientists, ethicists and nonscientists review the proposal from the drug developer and works to finalize a strict scientific protocol for the clinical trials.

• Phase 1 studies assess the most common acute adverse effects and examine the size of the doses that patients can safely take without a high occurrence of side effects. Initial clinical studies also begin to clarify what happens to the drug in the human body. From 20-100 patients will participate over the course of several months.
• Phase 2 studies are conducted in individuals who actually have the disease that the new drug is intended to treat. Researchers then assess whether the drug has a favorable effect on the condition over the short-term. Up to several hundred individuals will participate for up to two years.
• Phase 3 studies help to determine not only effectiveness, but also safety over a period of time. The best dose or range of doses is also determined. Up to several thousand participants will take the drug for one to four years.

Not all drugs that begin the three-phase process will make it to the pharmacy and medicine cabinet. Some are shown to be unsafe, ineffective, unprofitable, or all of the above. Of 100 drugs for which investigational new drug applications are submitted to the FDA, about 70% will complete Phase 1 and go on to Phase 2. About 33% of the original 100 will go from Phase 2 to Phase 3. And 25-30% of the original 100 will clear Phase 3. Of the original 100 experimental drugs, about 20% will be approved for sale.

Understanding the Design of Clinical Studies

Measuring the effectiveness of experimental drugs can be complicated, even though the process of investigation and analysis is grounded in science. Sometimes the disease simply goes away by itself (like a cold or allergy), varies in intensity and duration (like arthritis or asthma), or can only be measured subjectively by the doctor or patient (like depression or well-being). Scientists use "control subjects" to tease out these aberrations and subjective experiences.

In a controlled clinical trial, patients in one group receive the experimental drug, while those in a comparable group (the "controls") get either no treatment at all, a placebo (a "sugar pill") that looks like the drug, a drug known to be effective, or a different dose of the drug under study. Usually these test and control subjects are studied at the same time. Some studies continue even after the trial is stopped to allow comparisons before and after treatment.

It is important in organizing a group of people for study that they all be of similar age, weight, and general health status, or other characteristics (such as other treatments being received at the same time). Scientists use a process of "randomization" to eliminate problems where the statistical results of the study are distorted. Some studies have been disrupted when too many healthy people throw off the results, or when the drug reacts differently in women than men.

Further refinements to the study are made to remove any bias on the part of the researchers and patients. "Blinding" a study helps ensure that those participating in the study don’t know what treatment they are receiving/giving so that they don’t overrate the effectiveness of a drug or psychologically influence the results. A "single-blind" study consists of keeping patients from knowing whether they are receiving the experimental drug or a placebo. A "double-blind" study consists of neither the patient nor the data analysts/doctors knowing which patients got the drug. Only after the study is "unblended" do the participants know which drug is which.

Testing experimental drugs in people inevitably presents ethical questions. Is it ethical to give patients a placebo when effective treatment is available? Not all authorities agree on the answer. But the generally accepted practice in the USA is that fully informed patients can consent to take part in a controlled-randomized-blinded clinical trial, even when effective therapy exists, so long as they are not denied therapy that could alter survival or prevent irreversible injury. They can voluntarily agree to accept temporary discomfort and other potential risks in order to help evaluate a new treatment.

Resources for Participating in Clinical Trials

- Participating in Clinical Trials: What You Need to Know by Drs. Mary Sano and Christine Weber
- ElderCare Online's Medical Research Assistant
- http://www.alzheimers.org
- www.clinicaltrials.gov
- www.centerwatch.com
- www.drugstudycentral.com

Resources for Assessing Health Information on the Internet

- Health on the Net Foundation
- Hi-Ethics (Health on the Internet Ethics)
- Senior-Net’s Evaluating Online Healthcare Information

Source: U.S. Food and Drug Administration

Available from ElderCare Online™             www.ec-online.net             ©2001 Prism Innovations, Inc.