Clinical Trials of New Drugs:


A clinical trial is a test of a new drug in people. All new drugs must pass through several stages of trials before the Food and Drug Administration (FDA) approves them for general use.



If your loved one has tried available Alzheimer's treatments, and they have not shown the expected benefit, you may wish to enroll him or her in a test of a new as-yet-unapproved drug. These tests are reasonably open, though they all have eligibility criteria that might exclude your loved one. Participation in a clinical trial has both potential advantages and disadvantages. On the plus side, if the new drug works, your loved one gets to take it months and possibly even years before it is widely available. On the minus side, the new drug may not provide any benefit, and it might cause unwelcome side effects.



Before you make any decisions one way or the other, here's how the drug-approval process works, and how participation in a clinical trial might be a good option for your loved one.



How clinical trials work


When researchers identify a promising new potentially therapeutic compound, the first step in turning it into a drug is preclinical testing in laboratory animals. Preclinical testing usually takes from one to six years. The researchers test different doses of the drug in different animals with a variety of medical conditions in hopes of getting some idea what the drug is good for, the appropriate dose, and its side effects.



If preclinical trials lead researchers to believe that a new drug is both therapeutic and tolerable -- that is, not too toxic to use -- they ask the FDA for permission to use it on people in clinical trials.



There are three stages of clinical trials.

  • Phase I Clinical Trials. Phase I trials are small-scale safety tests. About 20 to 100 healthy volunteers (usually prison inmates) take different doses of the drug for several months to a year so researchers can learn how the human body absorbs and eliminates it, how the various body systems react to it, and what kinds of side effects it causes.



    Researchers usually have a fairly good idea how new drugs will affect people in Phase I clinical trials because human reactions are generally similar to those of laboratory mammals such as rats and dogs. But sometimes people and animals react differently, which is why the FDA requires Phase I trials.



    If the new drug's potential benefits outweigh the side effects that turn up in Phase I trials, the FDA allows it to proceed to Phase II.




  • Phase II Clinical Trials. Phase II clinical trials are longer, larger-scale effectiveness and dosage tests. Researchers recruit 100 to 300 people with the condition they think the new drug helps treat. They give them varying doses of the new drug to see if it works, and if so, which dose works best.



    Phase II trials use a design that is double-blind (neither the researchers nor the participants know who has received what) and placebo-controlled (half of the volunteers receive the new drug, while the other half receive a placebo).



    Phase II trials typically last about two years. While they focus on effectiveness and dosage, the researchers also continue to monitor the new drug's side effects.



    If the new drug appears to be effective at a practical dose without side effects the FDA considers too toxic, it is then approved for Phase III trials.




  • Phase III Clinical Trials. Phase III clinical trials mark the final stage of pre-approval drug testing. By the time a drug reaches Phase III trials, researchers are fairly confident that a known dose helps treat the intended condition and that the new drug is reasonably safe.



    Phase III trials last two to four years and typically involve several thousand individuals at medical centers around the country. Like Phase II trials, Phase III studies employ a double-blind, placebo-controlled design. In some Phase III trials, the placebo is a true placebo, a medically inert substance. In others, it is a standard medication already in use. In some trials, the experimental group receives just the new drug. In others, participants receive the new drug in addition to standard medication. The specific trial design depends on the specifics of the drug being tested and the condition it appears to treat. The FDA requires two Phase III trials per new drug to reduce the possibility that false-positive results will appear by some fluke.



    Many Phase III trials also offer an "open label" study. After the double-blind, placebo-controlled portion of the trial is complete, the researchers offer the new drug to all participants, who get to use the drug up to several years before the FDA approves it for general use.




  • Final Approval. After completion of Phase III trials, the sponsoring drug company submits its clinical trial data to the FDA, whose staff and outside consultants review it, and recommend either approval, denial of approval, or further testing. Final approval may take several years.


How to join a clinical trial


The Alzheimer's Association website contains a list of all the clinical trials of new Alzheimer's drugs currently enrolling participants. Information provided includes:

  • A discussion of what the new drug appears to do




  • Eligibility criteria for participation




  • The size and duration of the trial with its start and finish dates




  • A list of contact phone numbers of participating researchers around the country who can accept enrollees


For more information, visit the Diagnosis and Treatment section of the Alzheimer's Association website, and click on the link "participating in drug trials" under the heading Treatment Options.



"Safe" doesn't always mean safe


When the FDA approves a drug as "safe and effective," it does so based on data obtained from clinical trials involving several thousand individuals. Trials involving a few thousand people are a good way to pick up common side effects, the kind that happen to, say, one user in 10, or 20, or 100.



But many drugs have side effects -- some potentially quite serious -- that happen much less frequently. If a side effect happens to one user in 10,000 or 50,000, it may not turn up at all during the drug's clinical trials. It may take several years after the drug has been approved for researchers to realize that the drug has additional rare side effects.



All drug use should be monitored closely. But the newer the drug, the closer this surveillance should be because chances are that one or more side effects remain to be discovered.