The clinical trial process is the complicated system that is used to test drugs in people. There are different types of clinical trials, and different phases of clinical trials.

Types of Clinical Trials

Observational: In this type of study, participants are observed for the purpose of describing and measuring disease progression. Though no drugs are tested, this type of study is vital for developing methods that can speed the testing of new drugs. The Huntington Study Group trials PHAROS (completed), PREDICT, and COHORT are examples of observational trials. The upcoming Enroll-HD will be an observational study offered in Europe, North America, South America and Australia.

Open Label: In this type of trial, participants and doctors know that active drug is used for each participant. This method occurs in phase I, or first safety testing of a new drug. It also is used for providing experimental drug after a participant completes a placebo-controlled trial and during the process of drug approval.

Randomized Double Blinded Placebo Controlled: In this type of trial, participants are randomized by a secret lottery system to receive either active drug or inactive placebo. In this situation drug and placebo pills are designed to look the same, and neither the participant or the investigator will know who receives active drug or placebo. Only those who analyze results will know which participant (identified by number, not name) took active drug, and which did not. This type of trial gives best scientific results and is almost always required by the FDA for drug approval.

Phases of Clinical Trials

Phase I: Phase I tests for drug safety and tolerability over a wide range of dosages. This early phase includes includes a small number of volunteers, and looks for side effects at each dosage level. The drug's chemical effects on different body organs and how the drug is metabolized. This type of study is intensive and usually requires hospitalization (in a clinical trial unit) and takes only days or weeks of time.

Phase II: Phase II tests the drug in a dose range chosen from phase I. Though this type of trial can give preliminary efficacy results, or information about whether a drug may work, its primary purpose is to test for safety. This phase of testing needs more people, often in the range of 50-200 or more. This phase is measured in months of time for some drugs, and years of time for others. Time in this phase (and in phase III) in Huntington's greatly depends on what endpoint is tested. Often the endpoint chosen for phase III, is the one that gave the best results in phase II. Motor or cognitive endpoints will likely take less time than functional capacity endpoints. The "best" endpoint for neuroprotection is not known.

Phase III: After phase II studies suggest safety and effectiveness in a small number of people, the drug goes to phase III. Testing is on a much larger scale, requiring several hundred participants who take either active drug or placebo. This is by far the most expensive phase, taking millions of dollars. It is also the most lengthy clinical trial phase. Like phase II, time to results in phase III depends greatly on the endpoint. Using pharmaceutical industry statistics, only one of three trials that are successful in phase II will succeed in phase III. For trials in neurodegenerative diseases, the success rate is even less, closer to 1 in 10.

Regulatory Phase: If phase III trials are successful, the FDA review process begins. FDA review of drugs for Huntington's (an orphan disease) is faster than the average, but can add as much as a year (or more) to the process of drug approval. Or, as in the case of tetrabenazine, it may be longer. In this case, the FDA required more information and testing before drug approval is reconsidered.

Phase IV: In some cases, the FDA can require that the drug company perform another trial after FDA approval that monitors for side effects with prolonged use of the drug.