Patient enrolment is a common issue across many therapeutic areas in clinical research. Psychiatric disorders in particular represent a trial area with significantly high drop-out rates and poor patient recruitment. The reasons behind this problem, however, are rarely studied or understood. Despite this, new strategies devised over the last five years are beginning to reverse the trend, and both reduce stigma and increase awareness to funnel new patients into these important trials. 

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Introduction to the problem

Psychiatric disorders have historically had great difficulty onboarding and retaining patients for clinical trials. Major depression is one of the most prevalent and debilitating disorders which, in a 2015 review, showed a drop-out rate of almost 20% across 45 randomised clinical trials. The consequences of poor retention limit the development of tolerable, effective therapeutic interventions. In terms of poor enrolment, clinical trials investigating psychotic disorders like schizophrenia face a particular dilemma. 

Schizophrenia is a complex psychotic disorder with significant cognitive deficits including limited memory retention and poor attention capacity. The combination of cognitive impairment and psychosis has been associated with a decreased ability to consent. The inability to provide consent or retain the information to fully participate in a trial is a particular barrier for patient enrolment. Furthermore, patients’ poor attention to detail could compromise the reliability of results in clinical trials which contain elements participants are not used to, like placebos.

The impact of low enrolment and high dropout rates in psychopharmacological trials leads to poorer outcomes and can disproportionately affect the patient population in the long-term. In addition, it raises the questions of whether the selected study population are fully representative of the patient cohort.

Mental disorders: Anxiety and depression

According to a study investigating recruitment rates for paediatric depression, one of the main reasons for poor enrolment was due to comprehensive inclusion/exclusion criteria. 

For most clinical trials investigating one disorder, the exclusion criteria will prevent individuals who are co-morbid with other disorders from participating. In the case of major depression, it is very common for patients to also be diagnosed with other psychiatric disorders. As a result, the number of patients who achieve selected criteria of only having major depression is often very low. This raises the question of whether the screening of psychiatric disorders needs to take into account the high probability of co-morbidity and whether expanding the inclusion criteria outweighs low enrolment.

Failure to understand the pathology of psychiatric disorders could be a major flaw in patient retention. Patients diagnosed with GAD, for example, experience unfocused anxiety which can result in the individual seeking things to become anxious about. Recurrent clinical visits during a trial may elevate anxiety levels, which not only compromises the integrity of the results, but may cause them to drop out. Understanding the background of mental disorders could enable clinical staff to better anticipate potential factors that cause subjects to drop out and alter protocols accordingly.  

Psychiatric disorders: Schizophrenia

Observational studies are used by researchers to observe the efficacy and safety of treatment in a cohort without manipulation or intervention. These types of studies often highlight problems with patient retention in clinical trials. An observational study of schizophrenic patients on clozapine, an antipsychotic, found that approximately 50% of the 151 subjects discontinued treatment within the first six months. Two of the main reasons for patient drop out were noted as the patients’ own decision (40%) and non-compliance with treatment (36%). Almost half of the patients who dropped out made the decision themselves, which raises the question as to what it was that resulted in their discontinuation. 

One of the main limitations of the study highlighted the retrospective research design, which could be improved by introducing interviews to understand patients’ motives for dropping out. This further emphasises the need to better understand the pathology of the disease in order to view the clinical trial process from the perspective of the individual. Additionally, it was suggested that “extra support, education and encouragement” could be effective to support patients through the initial side effects of the drug.

Future recruitment and retention strategies

Failing to reach recruitment targets often reduces the impact of the trial and can result in the study being unable to answer important clinical questions. However, clinical research over the last five years has begun to investigate why these problems occur and how to resolve them.

In the case of schizophrenia, a 2018 study suggested that conducting further investigations into patients’ clinical history could determine the chance of consent. One suggestion from the study inferred that “An increase in the number of previous hospital admissions was associated with an increased likelihood of being approached for consent. This might reflect the fact that patients who have multiple hospital admissions have greater opportunity to be approached for consent simply by virtue of more frequent contact with mental healthcare services with repeated opportunities to be approached for consent across multiple admissions.”

The stigmatism of psychiatric conditions is a particular problem for enrolment in clinical trials, as patients conceal their condition to avoid judgement from others. This could lead to them avoiding research opportunities. Awareness of these conditions is one way in which organisations are attempting to boost recruitment for clinical trials. 

Public advertising, newsletters, and presentations to appropriate groups are some of the strategies that have been implemented to improve patient enrolment. In addition, resource manuals are often given to recruiters showing the scientific and psychological backgrounds of mental disorders to aid understanding in order to recruit the appropriate cohort. Furthermore, better patient support could substantially improve retention in mental disorder trials.  Periodic phone calls are another method used allow patients to communicate issues or fears that could be alleviated.

To discuss these topics further with sector experts, and to ensure you remain up-to-date on the latest in clinical development, sign up for Proventa International’s Clinical Operations & Oncology Strategy Meetings set for 27 May 2021.

Charlotte Di Salvo, Junior Medical Writer
Proventa International