Dimebon is looking good for Alzheimer's (AD). A 2nd AD trial (this one a PHASE 3) confirmed benefit seen in an earlier PHASE 2 trial. Benefits in memory, thinking, and behavior persisted during the year of treatment; in fact 81% of of AD participants were better than when they started the study. Based on these results Medivation is planning a larger PHASE 3 trial later this year. If results are positive, the company aims to start the FDA approval process in 2010 and the drug could move to patients shortly after. What about Huntington's; why was this trial slow to recruit?
The Huntington's Dimebon clinical trial started in July of 2007. Ninety participants drawn from 15 Centers of Excellence were to be enrolled for a 3 month trial. Nine months later in early March 2008, only 50 of the needed 90 participants have been enrolled. Why hasn't this gone more quickly? Look at it this way -- if enrollment had been completed efficiently -- we could have PHASE 2 results by now. Now at the end of March, enrollment has been completed. What a difference a month made!
Slow enrollment is a huge problem. The slower that HD recruitment goes, the longer it will take to get a successful drug to people. The entire community should be looking at this trial to identify problems that made recruitment slow initially, and the factors that sped it up this past month. And we need to correct recruitment errors as new trials for CoQ-10, creatine, and ACR-16 begin. And if trial participants aren't available to test them, it makes no difference how many new drugs are delivered down CHDI's pipeline.
Some of the Problems: Some Solutions
- Small numbers of HD patients are available. We must coordinate effort to identify and encourage HD families outside of standard academic centers.
- Exclusion criteria: This is cited as a significant factor in the Dimebon trial for HD. Though this is no longer the case, when recruitment began volunteers who wished to continue antidepressants Paxil® or Prozac® were not be accepted into the trial. When this restriction was lifted, recruitment was completed. We need to work hard on limiting exclusion criteria by designing innovative trials that study the effects, or allow substitutions for drugs commonly needed by HD people. This will be a ever-present factor in any HD clinical trial.
- Lack of awareness of clinical trial availability: This is probably a very big factor. Did you know that investigators in a trial must wait for a patient visit before informing them of the availability of a trial? If patients are seen only once or twice a year; this method will be unsuccessful for timely recruitment. There is no consistent system in place to inform those who might be interested. It will be critical for HDSA and other volunteer groups to take up this work and provide systems for communication with patients and their local doctors. In the case of the Dimebon trial, in an article this was communicated to the community in an article written by Marsha Miller.
- Inconvenience: Time lost from work or other activities. The Dimebon trial takes 8 visits over 4 months, with each visit taking 2-4 hours. The average working class participant may not be able to afford this. Has anyone ever thought of weekend or evening clinical trial assessments?
- Lack of support within the community such as providing babysitters, travel assistance, etc. Would this really be so hard?
- Fear of clinical trials is related to lack of understanding. Studies have shown that increased knowledge about the process of clinical trials decreases fear. Studies in breast cancer clinical trials show that if patient advocates facilitate the education and consent process, and help with documents, both enrollment and retention rates increase.
- Fears for loss of privacy. Be sure to include the details. Facilitate confidential genetic testing.
- Lack of motivation to participate in clinical trials may be a factor, but I don't think its a major one. Studies in other diseases, and in my early HD pilot project, survey information suggests that the vast majority of HD people want to know more about clinical trials and can be motivated to join.
Motivation and Hope
And last but not least; it is important to allow hope. Because practically speaking, there will be no motivation to join a clinical trial without hope. There are those who tell me and other patient advocates that we should be more laid back, and to be careful how we transmit the enthusiasm we feel about recent advances in research and drug development. They say this because they don't want to give false hope. Certainly a failed drug trial disappoints HD people, but no more than the present no drug reality we live. When EPA failed, HD families were disappointed; but it took only a few days till we got back up and went on. Believe me it is far worse when "for our own good" we are not allowed hope.
Allow hope; it's good for drug development.