While awareness of mental health conditions has increased and talking about them has become a lot easier, it remains an area of clinical investigation rife with challenges and controversies.
From the perennial problem of poor enrollment to the added issue of gaining consent from the mentally unwell, this post will explore the major challenges that beset mental health clinical trials. And, of course, the means to overcome them.
Failure rates are high in most clinical trials and the problem is no different for investigations into treatment for mental health issues.
Neurobiologist Kenneth L. Davis, president and CEO at Mount Sinai Health System in New York, blames it on new treatments producing “only small positive effects,” with placebos often as good or better than the treatment drug; and, as always, patient enrollment is “excruciatingly slow.”
The last point is particularly difficult with a persisting stigma associated with both the condition and seeking treatment for mental health as well as the ethical concerns of patients prone to suicide.
One of the issues, Davis says, is that the differences between mental health conditions are probably more stark than originally thought and greater focus should be on individual patients. Attached to the focus on the individual, however, is that inclusion criteria for clinical trials have changed to accommodate the nuances among mental illnesses.
However, a third reason why it’s difficult to enroll patients, is because of the existence of so many competing treatments, Davis argues. Most trials these days will likely only attract those who have not benefited from established treatments.
Having to send patients to trials for mental health is often regarded by the patient’s mental health clinician as a personal failure, Adwoa Hughes-Morley, National Institute of Health Research doctoral research fellow at the University of Manchester writes.
This presents a challenge as it could delay patients from enrolling in valuable research. Yet Hughes-Morley’s research shows both patients and healthcare professionals regard clinical trials as a valuable means of meeting mental health needs — especially in areas with limited resources. Patients enrolled in depression trials at least access healthcare they would not have ordinarily received.
When Prozac hit the market, the number of drugs for mental health, specifically depression, rose. The selective serotonin reuptake inhibitors (SSRIs, of which Prozac is an example) resulted in fewer side effects and were faster working.
Yet, as Mary O’Hara and Pamela Duncan write at The Guardian, 25 years later and the industry has yet to take “the next significant leap forward in psychiatric pharmacology.” However, a full one-quarter of the UK population and one-fifth of the US population will likely experience mental health struggles, making it necessary for pharma to act.
“In general, the larger companies have walked away from psychiatry… [and] many withdrew from neuroscience entirely,” NeuroPerspective founder Harry Tracy, Ph.D., tells O’Hara and Duncan.
Part of why this is so is because of the influx of cheaper and effective generic drugs. But, as Tracy says, it’s also because other areas of research are less controversial and expensive to pursue. Trial sponsors “decided it was easier to make money in oncology or diabetes and so they weren’t investing,” he explains.
Another challenge is cutting through the fog of uncertainty regarding new US policy about what constitutes a clinical trial for mental health. Confusion reigns over whether “basic research on humans should follow the same rules as studies testing drugs,” Jocelyn Kaiser at Science Magazine writes.
“Basic scientists who study human cognition — for example, using brain imaging with healthy volunteers — were alarmed to realize many of these studies fit the new clinical trial definition,” she adds.
A looming issue is that researchers will have to report their results in the ClinicalTrials.gov federal database even when not testing a treatment. The requirement has not been enforced as yet, and the National Institutes of Health is postponing a final decision until September 2019.
In the meantime, the NIH has stated that should researchers apply for the wrong funding opportunity due to this uncertainty of classification, they will receive “leniency.”
Patients participating in mental health trials are far fewer than those with physical disorders, according to research headed by Rashmi Patel, Ph.D., at King’s College London.
The assumption is that those with mental health issues are less willing to participate in studies. However, based on this study, it would appear that most patients with psychosis would participate but few were approached for consent. And the approached patients tended to be those that did not have such severe conditions.
The researchers suggest this could be due to study staff bias: They choose healthier patients for the sake of research. And this, in part, comes down to question of consent.
The researchers considered demographic and clinical factors associated with being approached for consent. They found through multivariable analyses that the decision to approach patients was made based mainly on mental health service-related factors rather than on the patients themselves. These factors included previous hospital admissions but fewer inpatients days.
The supposition is that these were patients that were less unwell but had previous experience in a health-related setting and therefore more inclined to be familiar with consent issues.
A team of researchers from India analyzed the major concerns or challenges when studying patients with mental health issues: the relationship between researcher and participant and its impact on informed consent.
There are two factors at play. The patients’ conditions can often impact their ability to make informed decisions, and the role and status of the researcher is usually one of authority.
The fear is that consent can become a matter clouded by this power dynamic. This might take the form of “providing wrong information, therapeutic misconception, unnecessary and prolonged investigations, exposure to harm related to investigations, pharmacological and nonpharmacological treatment, and malicious intimate relationship.”
However, when the relationship is founded on honesty, trust, and respect, this concern can be overcome. In order to achieve this, at least one researcher should be competent in the rights of patients with mental illness.
A quick recap is that informed consent is based on three important factors.
Providing information to patients about the research protocol, its likelihood of success or failure to treat their condition and the goal of researchers.
Competence refers to patients’ ability to understand the information told to them by researchers. When studying patients with mental illness, it is possible that their cognitive abilities could change during the study. Attention should be given to the ethics of this possibility occurring and whether or not to continue.
Autonomy refers to patients choosing and not being subjected to coercion or inducement. This important element shows a patient can decide on their own whether to participate rather than be influenced by the disease process or cultural or other extraneous factors. The researchers suggest there are solutions to these challenges.
As with all trials, information should be given in plain and easy-to-understand language. Patients should also be informed in their own language with attention given to cultural nuances that can affect meaning.
However, when it comes to consent, more needs to be done than simply completing consent forms. In the case of compromised competency of patients, trial researchers need to follow advanced directives and in their absence receive consent from the patient’s legally authorized representative or caregiver.
Consent should be ongoing rather than a one-off event. When the patient regains competence, their consent will need to be obtained once again.
While not quite in the realm of clinical trials just yet, virtual reality and other technological advancements could be used to help treat patients with mental disorders. The value is obvious when it comes to limited medical support resources.
Daniel Freeman, Ph.D., and psychology writer Jason Freeman conducted a study of “automated VR treatment for a psychological disorder” that replaces the real-life therapist with a computer-generated avatar.
The virtual therapist used a cognitive treatment programme to treat patients’ fear of heights. The randomized study sample of 100 patients either received VR treatment or no treatment. Even with some patients having lived for an average of 30 years with a fear of heights, just four or five half-hour VR treatments reduced patients’ fear by an average by two-thirds.
The writers say this is “at least as good” as treatment results from in-person therapy. Freeman and Freeman are not arguing to replace interpersonal connections between therapist and patient. Instead, they suggest VR can supplement therapy and cater to those without access to in-person therapy sessions.
Technological innovations aside, trial sponsors and managers will always need to put the patient first whatever the conditions. However extra care will always need to be bestowed upon the mentally unwell. Clearer governmental policies, more investment from pharma and stringent compliance with questions of consent will ensure trial staff operate effectively.
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