18 January 2018
Trial design: 4 ways to improve trials of pro-cognitive drugs in schizophrenia
Discussing the methodological considerations, and suggesting recommendations, for successful pro-cognitive drugs trials in schizophrenia.
Schizophrenia Clinical Trials series: part 3 of 4
- Improving clinical trials for pro-cognitive drugs in schizophrenia
- Patient recruitment: are we selecting the right patients for schizophrenia clinical trials?
- Trial design: 4 ways to improve trials of pro-cognitive drugs in schizophrenia
- How to select sensitive outcome measures in pro-cognitive drug trials for schizophrenia
Drug development is an expensive, risky and time-consuming process, requiring considerable financial and resource investment by pharmaceutical companies.
By ensuring the most appropriate and efficient trial designs are employed, we can ensure these studies are cost-effective while also maximising the scope to identify potential benefits for patients.
Developing consistent methodologies
Here we will discuss some considerations for improving pro-cognitive drug trials in schizophrenia, moving towards a more robust, consistent methodology in this area.
- Include a screening session to familiarise subjects with the cognitive test environment. The greatest change as a result of practice effects is seen universally across cognitive test batteries between the first and second exposure to those tasks. A familiarisation session at screening allows for more stable cognitive performance once dosing begins, enhancing the ability to detect pro-cognitive effects.
- Consider the effects of subject age. Younger adults, who have been affected by schizophrenia for fewer years, are expected to show the best outcomes following cognitive remediation (Corbera, Wexler, Poltorak, Thime, & Kurtz, 2017). Consequently, variance in the efficacy of pro-cognitive interventions may vary depending upon the age of the cohort, as well as clinical symptom profiles.
- Use consistent assessment timings. Psychiatric disorders, including schizophrenia, are associated with atypical circadian rhythms (Wulff, Gatti, Wettstein, & Foster, 2010). As a result, the time-of-day when an assessment takes place can be an important consideration. As is maintaining consistency in these timings across assessments.
- Take care with the duration of testing protocols. Lengthy testing protocols can cause fatigue and confound results. This should be an important consideration when selecting a suitable cognitive assessment battery.
Digitisation of clinical trials
To date, studies have adopted conventional trial designs; conducting a baseline assessment, randomising patients to a treatment or placebo arm then conducting further assessments at the mid- and end-points of the trial and at a longer term follow-up time point.
Incorporating more frequent cognitive assessments based on less resource-intensive monitoring, for example using smartphones, wearable devices or web-based testing may also help to identify pro-cognitive effects.
Furthermore, such technologies also present convenient methods for tracking symptoms and side-effects in real-time, so that potential drug-interactions may be better understood. Methodologies which employ digital technologies could revolutionise pro-cognitive trials.
How can you enhance the success of your pro-cognitive drug trials?
Corbera S, Wexler BE, Poltorak A, Thime WR, Kurtz, M M. Cognitive remediation for adults with schizophrenia: Does age matter? Psychiatry Research, 2017; 247, 21–27. https://doi.org/10.1016/j.psychres.2016.10.084
Wulff K, Gatti S, Wettstein JG, Foster RG. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease. Nature Reviews Neuroscience, 2010;11(8), 589–599. https://doi.org/10.1038/nrn2868