Designing clinical trials in psychiatry is challenging compared to a regular clinical trial. Clinicians and instructors have to handle participants who are mentally ill. They have to assume numerous factors before the clinical trial, where the main issue is taking informed consent, populations, measuring end-points, etc. 

There are many ethical laws and criteria for designing a clinical trial for psychiatric topics. The main problem is participants may have cognitive impairment and less ability to judge reality. Rules and regulations give inadequate guidance to address all ethical matters. The world medical association and other associations are operating various studies to develop adequate strategies to conduct psychiatry clinical trials effectively.

What do you need to consider before designing a psychiatry clinical trial?

Let’s understand a few important considerations while designing clinical trials for Psychiatry treatments.

1. Ethical issues
   1. Informed consent
   2. Substitution of informed consent
   3. Criteria for protection
2. Considerations for researchers designing psychiatric clinical trials     
   1. Introduction
   2. Objectives
   3. Population – Inclusion and exclusion criteria
   4. Trial design
   5. Control groups
   6. Scales      

Ethical issues

Clinical trials involving human beings are often seen critically by society. Exposing a patient to interventions and risks is unethical from the caretaker viewpoint. From the point of law, it is unethical to bring a patient to trials where safety is uncertain.

There should be a symmetry between risks and benefits. In a controlled clinical trial, the active group faces scientifically standard interventions where they have more benefits than risks. For the index group, as they are facing experimenting interventions, they have more risks than benefits. So the uncertainty of the trial is a prerequisite for approval.

Informed consent

The legal base of most medical research is informed written consent with concern for the participating patient. It’s a valid matter in clinical trials because research interventions target the new knowledge we try to gain. It doesn’t have any advantage for the participating patient. The concern researchers face during psychiatric clinical trials is the competence and capacity of the participating patient for consent. In that case, it’s a must to pay special attention to taking informed consent before taking a mentally ill patient to a clinical trial. 

Importance of an informed consent

1. Participating patients understand the significance of giving accurate information.
2. The patient may take the process seriously as his purpose.
3. From the researcher’s side, they would be able to deliver the information in a way that participating patients can understand and can be sure that the given consent is valid.

---

Click here to know about electronic Informed Consent in clinical trials

---

How do we assess the validity of the consent?

There should be appropriate information in the consent

1. Information about what?
   • We should provide clear information to the patient that interventions are conducted not only for his benefit but also for the sake of treating patients in the future. If we hide any information from the participant, he may become a victim of a “therapeutic misconception” That can lead to an uncertain validity of his consent.
   • Inform the patient about the risks and benefits he will have to face.
   • It is compulsory to advise the patient about the significance of his participation until the end of the trial.
2.  How to inform the patient?
   • Provide the information to the patient in his language. 
   • Deliver the details to the participant personally.
   • Let the patient understand it and ask the questions depending on the capacity of the patient’s understanding ability. 

There should be proper well-written consent.

1.  How do we assess the competence to consent?
   1. We can assess the patient’s understanding of the trial by asking him a few questions.
   2. Questions to check his factual understanding of the trial
   3. What does the trial mean to the subject personally?
   4. Understanding yes/no questions.
2.  Why should you assess competence?
   1. Not to overload an incapacitated patient.
   2. Concerning the participating patient 
   3. To have an idea of patients’ adherence to the procedures in the future.
3. Not to discriminate against the subject in front of capacitated individuals.

Substitution of informed consent

If the patient is not competent to consent, we must have a substitution method to continue the clinical trial lawfully.

1. Advance directive – define the instructions for the patient if he develops incompetence to give consent in the future. 
2. A power of attorney – Obliges the authorized person to verify how the judgments needed with consideration of the specifics of the condition in question are consistent with the purpose of the incompetent patient.
3. The competence of a lawful caretaker – is more limited because he is obliged to act only on behalf of the patient. Adherence to this rule is doubtful if we expect a group-specific outcome from the trial.

Since critically mentally ill patients can develop future relapses, psychiatrists should consider taking such patients in trials.

Criteria for protection

• The consent model
  • Every clinical trial needs valid and competent content since many interventions are non-advantageous for the participating patient.
• The benefit model
  • Even when the participant is incompetent, he can participate in the trial if the trial is beneficial for him. The world medical association registered this model in 1964.
• Risk minimization model.
  • According to this model,
    • Minimal risk should not exclude.
    • An advance directive or a relative of the participating patient can substitute the consent.

We can continue the intervention under two conditions if the trial passes the minimal risk limit,

• If the participant gives a specific consent
• If there’s a relative to monitor the participant’s health status during the procedure.

Protection criteria model

Research with incompetent patients when there are no benefits for that patients is ethically unacceptable. Under certain conditions, we can ethically continue trials in an incompetent patient even if he doesn’t have any advantage.

• When we can’t perform the trial in competent patients
• Substitute the consent with a legal caregiver.
• When there’s approval from the law
• The patient doesn’t refuse.

Considerations for researchers designing psychiatric clinical trials

The introductory section of the research proposal 

• The introductory section should contain a review covering the indications, medicinal alternatives available, and the experimenting treatments.
• Mention the scientific explanation of the trial, purpose, goal, targets, and importance of conducting the research for future treatment purposes in psychiatric patients.

Objectives of the research proposal

Ensure the consistency of the explanation and objectives. Objectives should clearly explain the importance and benefits of carrying out the trial for participating patients and future treatment processes.

Patient recruitment in a psychiatry clinical trial

Patient recruitment in a psychiatry clinical trial is more advanced compared to an ordinary clinical trial. You must pay special attention to inclusion and exclusion criteria depending on the psychiatric research you conduct.

Inclusion criteria

• The age of the patient depends on the trial going to perform.
• Diagnosis of the disease according to ICD 10/ DSM-5 criteria.
• Competence to complete the necessary evaluations.
• Willing to have a pregnancy test before the trial if the participant is a female.
• Competence to informed consent.
• Patients with acute psychotic episodes need full-time hospitalization.

Exclusion criteria

1. History of substance abuse and dependence
2. Critical medical illnesses(cardiac, respiratory, renal, or hepatic) according to the beliefs of the investigators.
3. History of intolerance and side effects of the particular drugs( previous severe attacks to certain antipsychotics)
4. Pregnant or breastfeeding mothers.
5. History of antipsychotic treatments.

Psychiatry Clinical Trial design

Psychiatric clinical trials often fail to get the maximum outcome. To achieve a better clinical result, researchers should design the clinical trial to meet the needs of the clinicians who make decisions about patient care. Researchers have to face many challenges while developing a clinical trial.

• Challenges to target population
  • Most patients have transport issues, financial issues, and the impact of society leads them to reduce their participation in a trial.
• The research team faces many challenges
  • Lack of experience as psychiatrists and investigators and financial issues to conduct the trial are some of them.

Control groups in psychiatry clinical trial

The control group is supposed to receive the placebo drug. Concern in selecting a control group in psychiatry trials is that in some psychiatric cases, there’s a response to a placebo. For example, a placebo response to depression is 30% on average.

It suggests that inactive treatment can indicate a considerable reaction. So it gives doubt about the outcome of non-placebo studies. Since a placebo can worsen symptoms, we should only use new psychoactive drugs over an active comparator.

Properties and scales of measurement in psychiatry clinical trial

Measurement scales explain how to categorize the variables and which statistical test to perform. Psychologist Stanley Stevens introduced four properties and scales of measurement.

1. Nominal
   • Explains the identity of any data
   • We can add, subtract, multiply or divide this data.
2. Ordinal
   •  According to the ordinal scale, data organizes in a specific order.
   •  On the ordinal scale, zero has no value.
   •  We cannot add or subtract the data.
3. Interval
   • A quantitative measurement scale. 
   • Shows properties from nominal and ordinal scales. 
   • Zero has a valid value. 
   • Can add or subtract the data.
   • Cannot divide or multiply the data.
4. Ratio
   1. Contain all the above three scales. 
   2. Zero indicates no value.

Every scale consists of properties to determine how to analyze the data.

• Identity – Every value has a specific meaning
• Magnitude- values have a relationship with each other
• Equal intervals- data points in the scale should equal.
• The minimum value of zero- the scale should consist of a zero value.

Conclusion

Neuroscience studies are developing day by day. But effective pharmacological methods still have to be researched. Conducting a clinical trial with mentally ill patients is a challenge because of the complexity of the populations, requirements of clinicians, financial issues, issues in taking informed consent, etc. Unlike conventional trials, Psychiatry clinical trials need a strategy in designing and conducting trials in Psychiatric patients.

According to the World medical association, there are several rules and regulations you have to follow before designing a clinical trial on a psychiatric case.

---

Do you need support for conducting clinical trials in Psychiatry?

Credevo offers expertise in designing clinical trials and providing strategies in challenging therapeutics areas like Psychiatry. Provide the required details below to connect with us and explore our services.

---