Awareness and Perception of Drug Trials among Patients with Mental Disorders

Mental disorders are generally characterized by abnormal thoughts, perceptions and emotions. These abnormalities may make an informed consent more difficult to obtain from psychiatric patients. The implementation of drug trials is being threatened by the decline in its overall frequency generally, especially in Psychiatry. This foretells a dearth of major breakthroughs in pharmacotherapy for psychiatric patients if they are unwilling to present themselves for drug trials. Insight into patient’s awareness and perception of drug trials will enhance the planning, design and implementation of drug trials among this vulnerable subpopulation. This was a cross-sectional study of one hundred patients attending the follow-up clinic of a tertiary psychiatric hospital. A proforma questionnaire to assess awareness and perception of drug trials was administered to participants. About half (51%) were aware of drug trials and 50% of the participants were not willing to participate in a drug trial. Sixty-five percent considered it highly risky to participate. Females were more likely to be unsure whether informed consent will be needed for drug trials. The married were more likely to be unaware of drug trials in clinical research. The unmarried were more likely to be informed about drug trials through the media. Findings are likely to have been influenced by the socio-cultural environment of this study setting. Drug trials among this population require an approach that will create an initial drug trial disorder—sensitive awareness and a design that will ensure that the consent process will take into cognizance the vulnerability of these patients; especially among females.

generally characterized by a combination of abnormal thoughts, perceptions, emotions, behaviours and relationship with others [1]. All these abnormalities may sometimes make working with someone with mental illness a difficult and an uneasy task. Furthermore, activities that will require an informed consent on the part of the mentally ill are even more difficult to engage in. Since clinical researches are studies in which people participate as either volunteers or as patient [2], finding people that are mentally ill to participate have always been difficult.
Clinical drug trials generate essential evidence for clinicians to make informed decisions for the care of their patient and discovery of novel drugs. As important as the process of drug trials may seem, its implementation is being threatened by the decline in the overall frequency of drug trials in general and in psychiatry in particular. Nierenberg noted that other fields of medicine are in the best of time as there had been a remarkable improvement in basic sciences like neuroimaging and genetics but psychiatry is in the worst of time due to the dearth of drug trials that assesses new drug interventions [3]. This foretells an unpalatable story for Psychiatry because there will be no major new breakthrough in patients' care if those that will need the care are unwilling to present themselves for clinical drug trials.
Little is known about the awareness and perception of drug trials among psychiatric patients. Successful implementation of drug trial among psychiatric patients will require an in-depth knowledge of the scope of awareness and perception of these patients. This is likely to be influenced by the socio-cultural environment of the study setting.

Definition of the Research Problem
Drug trial is one of the most potent method for evidence based medicine [4]. If science (medicine inclusive) is predicated on time tested evidences, then a decline in such evidence generating endeavours like drug trials can spell doom for the specific body of knowledge. It would not be an easy task to know the rate of drug trials in a sub-Saharan African country like Nigeria, but the best guess will be that a poor economy will affect the rate at which researches and by implication, drug trials are being done [5]. There are many factors that militate against people getting involved in drug trials in psychiatry among which are people awareness and perception of drug trials. Most patients suffering from mental illness are not receiving any form of treatment, albeit subjecting themselves for research endeavours that will improve their treatment and others' will help advance treatment modalities [6]. Knowing the level of awareness of the patients suffering from mental illness to drug trials and their attitude towards it will go a long way in helping the clinicians and researchers in making informed decisions about the best form of design and protocol to develop in a drug trial.

Definition
According to the world health organization (WHO), a clinical trial is any re-A. S. Adebisi, S. Sale search study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes [7]. While Clinical trial entails all types of medical interventions, drug trial is a subgroup of clinical trial that subsumes the use of drugs/medications as the form of intervention in the experimental study called clinical trial. It has been reported that less than 10% of Americans participates in research studies and less than 10% reported knowing "a lot" about drug trials [8]. Another study among Americans also revealed that 32% were willing to participate in cancer clinical trials [9]. In developing countries where lower number of such research activities are carried out, the level of awareness is expected to be much lower.

Goals
The two major goals of drug trials are to learn about the efficacy and effectiveness of a drug and to learn about how safe a drug is. These goals are further typified by what the researchers want to achieve with the trials. This may thus be in form of Prevention, treatment, diagnostic trials, screening and to assess patients Quality of life [10].

Phases
Most researchers go with the notion that there are four phases to a drug trial (Phase 1 -4), but a few others believe there are five stages to it (Phase 0 -4) [11] [12] [13].
Phase 0: These are usually optional. It is the first-in-human trials of drug. It is equivalent to the usual test dose given to patients on potentially dangerous drugs. Here, a sub-therapeutic dose of the drug to be tested is given to a small group of individuals (10 -15 subjects) and a preliminary data on the drug pharmacodynamics and pharmacokinetics are collected.
Phase 1: This is often the first in-human trials. It is a testing that takes between 20 -80 subjects. It is to evaluate safety of the drug and determine the safe dosage range. It is also the stage at which side effects of the trial drug is being identified.
Phase 2: This stage deals with larger number of subjects (100 -300). It also determines efficacy of drugs and evaluate some less common side effects. Since rarer adverse effects come to the fore with larger number of people, this stage helps in identifying uncommon side effects of the drugs being tested.
Phase 3: This entails testing with an even larger number of subjects (1000 -3000). This is to confirm efficacy, evaluate effectiveness, monitor side effects and then compare these to some commonly used treatment. This is to ensure that information that will allow it to be used safely is collected.
Phase 4: This is the post marketing phase where continuous monitoring of the marketed drug is done. Information about the drug is collected throughout the lifetime of the drug use.

Who Can Participate in Drug Trials?
Generally speaking, anyone can participate in drug trials once an informed con-Open Journal of Psychiatry sent can be gotten. However, some special groups have more stringent criteria than others. In the US, people that are above 55 years are often excluded from drug trials because of their greater health issues and their different physiology in drug metabolism when compared to young people. Also pregnant women (fear of teratogens), children and people with unrelated medical conditions are often excluded [14].

The Process of Drug Trial
Investigators usually recruit subjects that have a predetermined characteristic into the drug trial over a period of time. There is usually a study protocol that stipulates all the aims, objectives and other terms of reference of the study as the guide to each investigator. Consenting subjects will be administered the drug or placebo (as the case may be) and data about the subjects' health will be collected for statistical analysis [15] [16].

Safety Issues Why Protocol Eligible Subjects Refuse Participation
The responsibility of safety of subjects is shared among the sponsors of the drug trials, the local investigator who implements the study, the ethical committee of the institution on whose subjects the drug is to be tested, and the regulatory agency of the country where the study is being done.
Some studies have been done on why protocol eligible study subjects refuse to participate in drug trials and they came with different arrays of reasons. According to Julie et al in their 2011 study, among the commonest reason for refusal in drug trials are the research protocol issues like long duration of study, use of invasive procedures like setting IV line, collecting blood, taking other body tissues sample etc. Subjects are also often weary of the side effect of drugs and the risk of symptoms getting worse during the drug washout period [13].
Some study schedules are also inconvenient to a large number of subjects like studies held during work hours, studies in which patients will have to travel a long distance and lack of flexibility in the participants' schedule. improving the quality and effectiveness of randomized control trials in psychiatry and suggested that the study subject sampled should be as closely related to the target population as possible. They also suggested the use of a culturally acceptable intervention and elimination of bias through the use of controls as the solution to bad study quality being experienced in psychiatry [20].

Benefits
Drug trials participation is beneficial to the participants and the society at large.
It is the basis for generating essential evidence for clinicians to make informed decisions for the care of their patients [3].

Methodology
Setting: The Federal Neuropsychiatric Hospital Kware, Sokoto is a tertiary health care facility located in Kware local government area of Sokoto State, Nigeria.

Study Design
It was a cross-sectional study involving patients managed for psychiatric disorder and attending the follow-up clinic at the hospital from August 2017 to November 2018.

Ethical Consideration
Ethical committee of Federal Neuropsychiatric Hospital Kware, Sokoto was sought to ensure that the work meets ethical standards and approval was granted by this committee.

Questionnaire
A proforma was developed containing items on sociodemogrphic factors. Questions to assess awareness and perception of drug trials was also included. This was designed to elicit the following: 1) Socio-demographic data e.g. gender, marital status, age, sex, educational Open Journal of Psychiatry level, occupation and residence.
2) Awareness and perception of the processes involved in a drug trial. See Appendix A.

Procedure
Participants were recruited consecutively through personal contact as they came for follow-up care at the clinic. Potential participants (Those that satisfy the inclusion and exclusion criteria) were informed of the nature of the study, the anticipated amount of time required for participation. Patients were informed that their participation is voluntary and that there are no penalties for non-participation. Informed consent was obtained from all participants before the administration of the instruments.

Patient Selection
A sample size of one hundred patients that satisfied the International Classification of Diseases Version 10 (ICD-10) for research were recruited for this study.
This sample size was based on the findings of recent studies were most drug trials are carried out. It was reported among American adults that less than 10% knew "a lot" about drug trials [8]. In developing countries this is expected to be much lower.
The ICD-10 manual contains the diagnostic criteria for various mental disorders for research purposes. Participants, documented symptoms and signs in the medical files must satisfy these criteria to be recruited for the study. Patients with active psychotic symptoms and co-morbid medical conditions were excluded from the study.

Results
A total of 100 patients satisfied the ICD-10 Diagnostic criteria for research for various mental disorders. 56% were males while 44% were females. Most of them were married (67%) and unemployed (67%). They were mainly of the Hausa  Table 1.
When participants were asked if they were aware of drug trials, about half (51%) reported being aware and 49% were not aware. See Figure 1.
Also, 50% of the participants were not willing to participate in a drug trial.
65% percent considered it highly risky to participate. Females were more likely to be unsure whether informed consent will be needed for drug trials (χ 2 = 7.65, p = 0.02). The married were more likely to be unaware of drug trials in clinical research (χ 2 = 9.30, p = 0.002). The unmarried were more likely to be informed about drug trials through the media. Full details are as shown in Table 2. Full details are shown in Table 3.

Discussion
The main thrust of this study is on the assessment of awareness and perception of drug trial among patients with mental disorders. Majority of the participants Open Journal of Psychiatry were young adults which implies that the decision to participate in a drug trial will depend a lot on the individuals themselves. This is because participants in the extremes of life (children and elderly) require inputs from significant family relatives which are usually overriding. Inability to properly engage these young adults may actually hinder the implementation of the protocol despite the willingness of relatives.
Majority were also unemployed; this can make these individuals vulnerable to coercion or abuse in drug trials. About half of the participants were aware of drug trials. This finding probably reflects a general knowledge of drug trials but not a depth of knowledge sufficient for participation in such research activities.
This finding is lower than that reported by studies done in western countries like America were 74% and 80% were reported in two studies respectively [9] [21].
However, the unwillingness of half of the participants to participate in drug trials portends a not very good outlook among these subjects in drug trials research. There are mixed findings in other challenging disease conditions like cancer where about 69% have been reported to be willing to participate in drug trials [22] and over 80% unwilling to participates [23]. Furthermore, the greater percentage of participants' perception of drug trials as highly risky will likely also negatively affect participation. A study conducted in about 68 countries reported that 90% believed drug trials are generally safe [24], while another study among American adults reported that 43% considered it too risky [9].
The finding of the married being more likely to be unaware of drug trials may be due to majority of the participants being married which might have influenced the finding of the association of married participants with unawareness of drug trials. This may also require further investigation into other possible reasons for this finding. The unmarried were however more likely predictors of awareness through the television. This is in keeping with the increased use of media platforms and internet in the last decade especially among young adults in this country. It is possible that they have heard more about the litigations of drug companies due to failed drug trails and complications from the media and internet. One study found increased use of the internet as a predictor of drug trial awareness [21]. Little is known through the media about its importance and benefits. This might also have influenced the greater number of participants considering drug trials as highly risky. This impression is also seen among young adults in productive age group (24 -34 years) higher preference for the use of the elderly in drug trials. This may likely be due to the assumption that risky research activities should be done among people that a closer to death than among young people. Those below 24 years and above 34 years were more likely to recommend healthy individuals for drug trials than the young adults. It is possible that older people and the younger age group (below 24 years) consider the 24 -34 years age group as the healthy ones. The finding of females' association with being unsure of whether their consent will be needed may likely reflect an underlying social-cultural pattern as pre-Open Journal of Psychiatry viously described [25]. This socio-cultural pattern creates a need to be holistic during the consenting process in drug trials. This is because socio-cultural factors play pivotal role in influencing the decisions of participants. In typical Northern Nigeria the consent of married females is usually determined by their husbands' permission to participate in such research activities despite its necessity or urgency. Designs of drug trials in such socio-cultural setting will therefore require proper engagement with their husbands even before married female participants are approached for participation.
High socio-economic problems have been associated with these patients in previous studies [26] [27] this can be linked to the high rate of unemployment and lack of formal education of majority of the participants in this study. This makes participants more vulnerable to inducements and coercion in drug trials.
The participants of the minority tribe (non-Hausa) were more likely to be aware of drug trials from reading newspapers and to request for other forms compensation in instances of adverse drug reactions than the predominant tribe (Hausa) during drug trials. These findings may be due to the rather small number of the minority tribe rather than inherent attributes. However further examination of these findings in future studies may be necessary.

Conclusion
The level of awareness of drug trials among psychiatric patients appears to be poor and majority of them consider it a highly risky research to participate in. Socio-economic problems encountered by participants with psychiatric disorders need to be considered in the design of drug trials among them. The female patients are likely to be more vulnerable to coercion and abuse in such research activities.

Recommendations
There should be concerted effort to correct the wrong perception of drug trials through the use of media platforms and public enlightenment programmes.
The design of drug trials among psychiatric patients should adequately include a legal framework that takes into cognizance their vulnerability and how to ensure that the consent process is not compromised. This will require a multidisciplinary team of experts in the field of Mental Health who will provide guidance on the development of a protocol that shows an understanding of the disorder and its psychopathology.
Researchers should consider the addition of long-term benefits in the research design to participants that will be supportive, considering the continuous social challenges they face due to mental disorders. This will go a long way in sustaining the quality of life of participants beyond the research period and encourage participation.

Limitations
It was a cross-section study and may not be sensitive to changes in awareness