There is widespread demand for access to medicinal cannabis products by patients. Yet very few Australian doctors currently prescribe cannabinoid-derived medications. Will emerging clinical trial evidence reduce the reluctance of GPs to prescribe these medications? In this blog, we’ll provide a basic overview of setting up a clinical research trial for medicinal cannabis. Reading time: 3 to 4 minutes.

Clinical Trials: Setting up Your Cannabis Research Study

The hesitancy surrounding doctor-prescribed cannabis products is intrinsically linked to:
- limited clinical evidence concerning the efficacy and safety of medicinal cannabis
- the lack of medical-sector acceptance of a drug that lacks sufficient efficacy and safety data
There’s also a lack of dosing knowledge.
Plus, many medical professionals are unclear about how genetic factors might change a person’s responses to cannabinoid medications.

Currently, many top Universities, Medical Schools and Teaching Hospitals are setting up their medicinal cannabis research studies. So what’s involved?

How to Set Up a Clinical Trial for Medicinal Cannabis Products

Clinical trials provide scientific evidence and safety data for prescription medications, including cannabis-derived medications or medicinal cannabis.

While the evidence base on cannabis-medications is currently pauce, Universities are ramping up their research studies with an influx of new research funding. It will take some time to attain and evaluate study results. However, as evidence grows, it is expected to reduce the number of Doctors currently failing to prescribe medicinal cannabis for intractable conditions.

The value of clinical trials and evidence-based data

This type of clinical investigation is the most effective approach to obtain statistically relevant data for the efficacy and safety of cannabinoid-based products. Clinical study data:

is necessary to scientifically assess pharmaceutical safety, product efficacy and patient/public health risks
- Including unapproved medicinal cannabis products and
- Various products, creams and beverages being touted on the market in certain countries

How do you set up Clinical Trial using medicinal cannabis product?

Clinical trials involve a great degree of administration and approvals. Tasks include setting up the trial, recruiting participants, attaining patient consents, attaining cannabis-derived medications, and conducting the study according to strict clinical trial protocols which also govern recruitment, reporting methods, data record-keeping and distribution of research findings.

Clinical Trial Notification (CTN) scheme

Once a decision has been made to conduct a study under Clinical Trial Notification (CTN) scheme, the sponsor (the academic, individual or organization that initiates and takes responsibility for the clinical trial), must first ensure that they understand the TGA requirements for clinical investigation under the Clinical Trial Notification (CTN) scheme.

In the Australian Clinical Trial handbook, there is a National Statement on Ethical Conduct in Human Research (The National Statement) that all researchers must understand and comply with. This statement highlights the importance of implementation of GCP in the clinical investigation, including the Sponsor’s responsibilities as per ICH Guidelines for Good Clinical Practice (GCP) annotated with TGA comments (TGA ICH E6 GCP).

It is possible for the sponsor to delegate some of their clinical research responsibilities to a contracted research organization (e.g., such as monitoring for GCP compliance, study data management, pharmacovigilance, manufacture/supply of the investigational product, and similar obligations).

However, the ultimate responsibility for GCP and regulatory compliance remains with the Sponsor of the study.

Why this GCP so important in a clinical trial?

Adherence to GCP and regulatory requirements is a necessity to:

ensure the protection of the study trial participants (study participants)
obtain quality data that can be used to appropriately assess the safety and efficacy of the medicinal cannabis product under investigation

The dangers of non-compliance in a research study

Non-compliance to these requirements will result in uncertainty in the reported safety and efficacy findings
It leads to questionable validity of the collected data and/or lead to
Safety risks to participants

Who will conduct the Clinical Study and where?

The Sponsor does not tend to conduct the Clinical Investigation. It is the Clinical Trial Principal Investigator that the Sponsor assigns to lead the study. The exception is in research studies where the Sponsor is also the Principal Investigator conducting the study.

The Principal Investigator must be professionally and legally responsible to conduct the trial in accordance with the HREC-approved protocol.
As such, the Sponsor must identify an Investigator that is qualified, by education and experience, to conduct the Clinical Investigation(s).

Principal Investigators for Cannabis Studies

The choice of an Investigator may also depend on the intended use of the tested medicinal cannabis product.

For example, if the intended use of the investigational product is treatment of cancer symptoms, the selected Investigator might be a Specialist Oncologist.
All clinical studies require certain expertise and clinical rigour as well as precision record-keeping and designated recruitment processes.
Thereby, a study also needs to be conducted at clinical sites where the personnel are suitably qualified and experienced to support the Investigator in the conduct of the Clinical Trial.

Multi-Site Studies

Depending on the size of the trial and to help ensure recruitment of the required number of study participants, the Sponsor may need to consider the inclusion of more than one clinical site to conduct the research. This is called a ‘multi-site’ clinical research trial and involves careful coordination, overseen and managed by specially trained clinical trial personnel and the Principal Investigator.

Design of the cannabis research trial

The trial should be designed to ensure:

the well-being of the participants is not compromised; and
the data collected will provide answers and information required to achieve the clinical trial objectives.

Considerations to be taken when designing the trial

Considerations for your medicinal cannabis trial include, but are not necessarily limited to, the following components.

What is the intended use of the tested medicinal cannabis product?
- Has this or similar formulation been used for any other indication(s)?
- If yes, what were the study findings?
What type of data needs to be collected to demonstrate the safety, tolerability and/or efficacy of the tested product?
- Are assessments of dependency of the medicinal cannabis product being considered?
- E.g., if the product has a high THC content and is intended to be delivered over an extended period of time, is dependency a recorded potential complication or potentially harmful effect?
Are there safety data available for the proposed formulation and the dosage regimen of the medicinal cannabis product planned to be administered?
What is the number of participants required to be included in the study to achieve sufficient data collections so as to adequately address the primary study objectives?
Are the participants healthy volunteers or are they patients already receiving therapy for the existing condition?
What are the clinical endpoints of the study?
What is the stability of the tested medicinal cannabis product?
- Does the product require specific storage and/or handling requirements?
- How is it to be administered?
- Does it require any handling/preparation or specific medical device for its administration?
What type of expertise would be required for an appropriate Safety oversight of the conducted study?
What are the HREC, TGA and/or ODC recording and reporting requirements?

Required Approvals to Conduct a Clinical Study

No cannabis research trial can begin without first attaining HREC approval.

The research protocol(s) and study proposal naming the Investigators, study Sponsor(s) and medication formulations, must first be submitted to the relevant HREC (Human Research Ethics Committee).

Documentation requirements for research study proposals are often extensive. Documents might require special TGA approvals for unapproved medications, participant consent forms, data collection, data analysis and reporting methods, and prior study data, if available, in relation to the medication’s efficacy and safety.

The application and study design must list key study factors.

These factors include the study population, inclusion and exclusion criteria, dosing, safety, adverse effects reporting (SAEs) criteria and reporting, data collection timeframes and parameters, and the commencement date and end-date of the study. Funding of the study must also be disclosed.

When a study is proposed, there may be frequent communication back and forth between the HREC and the Principal Investigator about the protocols and related consents. Often, clarification of the protocols and/or changes to the study design or participant inclusion and exclusion criteria may be requested by the HREC, prior to granting study approval.

The HREC has one primary goal in mind: protection of the study participants while attaining valid data about the drug’s efficacy and safety.

Once the investigator obtains the approval from the HREC, the sponsor notifies TGA for the planned clinical investigation (see Access to medicinal cannabis clinical trials under the CTN scheme blog for more details).

Any additional study considerations?

In accordance with the current legislation for obtaining, supplying and administering medicinal cannabis products, Commonwealth and state approvals must be granted to the investigator and the pharmacists for the purpose of conducting clinical research.

The clinical site must also ensure appropriate records on the medicinal cannabis product that is stored securely on the premises.
This includes all transactions of the medicinal cannabis products, for the length of the clinical study and then for as long as specified in the clinical study protocol.
Appropriate and approved procedures must also be in place for disposal and/or destruction of any unused medicinal cannabis product.

Quality System procedures should be implemented at both the Sponsor’s site and the Investigator’s site. A quality system ensure that all trial-related activities, including data collection and data management, have been conducted according to rigorous clinical trial standards and HREC-approved study protocols.

Data must also be collected and recorded in accordance with the approved protocols, and applicable regulatory and GCP requirements. This includes the specific GCP requirements related to medicinal cannabis products.

Will more doctors start prescribing medicinal cannabis once further research data is accumulated?

The answer, most likely, is yes. However, this will likely only occur after enough long-term study results have left Doctors feeling more confident about prescribing medical marijuana for certain conditions. This includes evidence-based guidance about the best treatment forms (medication delivery methods), doses and treatment durations for chronic illnesses, debilitating health conditions or diseases.

Valid safety and efficacy data accumulated in clinical trials would certainly assist in overcoming the current hesitancy in prescribing medicinal cannabis products to patients where traditional treatment methods have failed.

This is likely to help patients gain better access to the reported benefits of medicinal cannabis, which might improve their lives and/or their treatment tolerances and reduce their pain levels.

But until studies providing clinical evidence on recommended dosing, safety and efficacy for medical marijuana, many Doctors will remain on the fence about prescribing medicinal cannabis to their patients. While this is frustrating to individuals with conditions that are non-responsive to currently-available treatment options, many Doctors are simply cautious of making a mistake when so little valid data exists.

The result is that people with break-through cancer pain, arthritis, MS symptoms, or PTSD are increasingly frustrated at not yet being able to readily access medications they believe might be of help in reducing symptoms.

That noted, numerous anecdotal reports, preliminary research trials and patient-case studies, have indicated positive impacts for cannabidiol based medications.

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