15 October 2018
Three ways you can design better drug trials for schizophrenia therapeutics
To date, no effective drugs have been developed to address cognitive dysfunction in schizophrenia. Here we will highlight the three main methodological challenges which may be contributing to these high failure rates, and propose potential practical solutions to these problems.
Schizophrenia is characterised by the occurrence of positive symptoms (e.g. hallucinations or delusions) and negative symptoms (e.g. social withdrawal and lethargy), which affects more than 21 million individuals worldwide. Many people with schizophrenia also exhibit impairments in cognition—the various mental processes relating to the acquisition, storage, manipulation, and retrieval of information.
Cognitive impairments associated with schizophrenia (CIAS) present considerable costs, functional and financial, for both the patient and society in general. Consequently, pharmaceutical companies have made considerable efforts to tackle this common aspect of the condition, but an effective medication has yet to be developed.
So, why have new CIAS therapeutics remained elusive despite all this research? Sometimes they fail simply because of the nature of the drug products themselves and the challenges associated with developing any drug—such as low efficacy or safety issues. However, another significant (and yet avoidable) factor that can lead to the failure of a CIAS therapeutic is a flawed study design.
Here we will highlight the three main methodological challenges which may be contributing to these high failure rates. For a full discussion on how you can adjust the set-up of your clinical trials to more accurately evaluate the therapeutic potential of pro-cognitive drugs, please download our eBook here.
1. Be more selective when recruiting patients for pro-cognitive drug trials
At present, patients are often recruited into pro-cognitive drug trials for schizophrenia based on an established diagnosis and psychosis severity. This protocol is not ideal for CIAS studies, since psychosis severity does not impact on CIAS, individuals who exhibit only minimal cognitive impairment or those whose performance falls within a healthy range may be included in the study sample.
One method you can use to improve patient recruitment is with a pre-screening step. Although pre-screening has not been a requirement of pro-cognitive drug trials to date, the inclusion of unimpaired patients may significantly mask the effects of a compound by artificially inflating baseline performance. Therefore, if you proactively screen into your trials individuals with a measurable cognitive deficit, you are more likely to demonstrate the efficacy of your drug on the target patient group.
You may also wish to re-analyse the clinical trial data you have already captured. By stratifying your clinical trial patients into high- and low-functioning group, you may identify those individuals most likely to benefit from a specific pro-cognitive drug, and help increase your chances of showing a statistically significant improvement when your drug was administered. In turn, this can give shelved therapeutics a new route to market.
2. Adjust your study design to accommodate the needs and symptoms of patients with schizophrenia
In addition to improved patient recruitment, designing your pro-cognitive drug trials with the specific needs of patients with schizophrenia in mind can have a significant impact on your results. For example, patients with schizophrenia can find unfamiliar situations or environments difficult, and this unfamiliarity can impact on their performance during assessment. In turn, an improvement between first and second exposures to a cognitive task can often been mistakenly attributed to the efficacy of a drug when, in reality, the subject has simply become more comfortable within the testing environment. Therefore, inclusion of a ‘familiarisation session’ prior to treatment and testing can help to reduce test anxiety and alleviate this biasing effect, allowing for a more stable performance once dosing begins.
Digital technologies can also help address this issue, by bringing the trial into patient homes. Smartphones, wearable devices and web-based testing can dramatically increase the frequency of testing and are all convenient methods of evaluating symptoms and side-effects in real-time. Using digital technologies in this way has the potential to improve testing compliance, increase data reliability and reduce cost.
3. Ensure your outcome measures are relevant and sensitive
When designing your clinical trials, it is crucial to first identify outcomes that would provide clear evidence of drug efficacy. Working with outcomes in mind allows you to select cognitive tests that are sensitive enough to detect even subtle effects on patient cognitive performance. For more information, download our eBook, which contains a number of case studies that really showcase the importance of this point.
Learn more about improving your pro-cognitive drug trials
Running pro-cognitive drug trials is challenging. Recruiting the most suitable patients, designing the most relevant trials and selecting the most appropriate outcome measures will all impact on your success.
To help, we created an eBook entitled ‘Enhancing clinical trial success for pro-cognitive drugs in schizophrenia’. In it, we provide insights designed to help you to deliver effective pro-cognitive drug trials that are run smoothly and to time, ultimately increasing the likelihood that your CIAS therapeutic will successful make it to market.