Many of us typically think of Alzheimer’s Disease (AD) when we hear the word “dementia”. This is a fair assumption since AD is indeed the most common type of dementia, and accounts for up to 80 percent of all cases. Because of its prevalence, the AD drug market is highly profitable, with an overall value estimated at 3.6 billion USD in 2017 and forecasted to reach 6.4 billion USD by the end of 2025.
Unfortunately, many sponsors struggle to complete their AD clinical trials before being able to enter into this market. Sponsors face many challenges in getting an AD drug approved, but the most common issue that we’ve seen is low enrollment, which is often traceable back to an overly complicated protocol. With enrollment periods as long as 51 months in some cases, a less complex study design is often necessary to help sponsors recruit more patients in less time. The protocol writing process needs to have reasonable compromise on certain elements. In today’s blog post, we will cover two specific elements – exclusion criteria and schedule of events – that can use a little wiggle room during the planning stage.
Over the course of protocol writing, more and more exclusion criteria are added to help sponsors reduce variables and produce higher-quality data. While many exclusion criteria are useful in eliminating confounding variables, certain exclusions of comorbidities in elderly patients can be negotiable. These comorbidities can be broken down into two categories:
- Age-related: The bulk of AD patients are 65 and older and, understandably, have other age-related disorders like hypertension and diabetes. Certain age-related comorbidities like these should not be a huge weeding-out factor if there is a balance between selection and quality. For example, it may be unnecessary to exclude patients with a history of hypertension that is now controlled and stable on medication. All stabilized patients can be considered a possibility for the study and the rest with uncontrolled illnesses can be excluded.
- Psychological: Restrictions on common psychological comorbidities, like depressive disorder, can also be negotiated. Up to 40 percent of AD patients suffer from depression, and sponsors can miss out on a sizable number of AD subjects if these patients are excluded – whether they are stabilized or not. Again, we believe that AD patients with depression should be considered if they are stabilized with the appropriate medication and dose. Patients with uncontrolled psychological disorders are a danger to themselves and the trial, but stabilized patients should pose less of a threat.
Schedule of events
Treatment design also poses significant challenges. It can be highly valuable to tailor the schedule of events to be as convenient as possible for both participants and caregivers (who are also required in many studies alongside patients). The AD patient population is very reliant upon study partners/caregivers, and these caregivers are just as critical to the overall success of the study as the patients themselves. There are two factors to be mindful of:
- Total duration of the clinical period: the longer the treatment, the greater the burden on both participants and study partners. Treatment periods can easily last up to two years, which is intimidating to both parties. Lengthy treatments are especially challenging in severe AD studies, where overwhelmed caregivers who are at risk of burning out may refuse to participate. Therefore, treatment periods should be reasonable enough to entice enrollment.
- Frequency of office visits: given the time-consuming assessments and exams, the visit frequency should also be sensible while still preserving the integrity and quality of the trial. It is understandable that in certain cases, like phase 1 studies, the number of visits is necessary to determine safety of a novel product. However, if too many visits are required within a given time-frame, the patient may no longer want to go or the caregiver may not have the time to bring the patient to the site. Ideally, the visit frequency should be spread out or reduced when possible.
AD trials can seem like a difficult barrier to overcome for many pharmaceutical companies, but growth in the AD pharmaceutical market makes it a mountain well worth climbing. Fortunately, the challenges involved in running Alzheimer’s studies are well understood, and CROs are already beginning to account for them and build mitigation strategies directly into trial and program plans. For programs without these mitigation strategies and/or with programs that may be faltering, some CROs (like Biorasi) have made themselves into experts on bringing these failing trials back from the brink and completing them successfully, providing options to struggling sponsors.
If you have an AD trial whose success you may be worried about, contact us and ask about our free trial assessment – a confidential, no-commitment option that can let you know exactly where your program stands, and what it would take to get it back on track.