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How to select a patient population for your Phase 0 trial

Milou Noltes, MD, PhD

For reliable Phase 0 study data, it is key to select the right patients to participate in your study. This mainly depends on your research question and desired outcomes in terms of pharmacokinetics, biodistribution and on- and off-target binding. There are a few steps you can follow to make the process less complex.

Four key things to consider when selecting your patient population.

Overall, during the patient population selection process, you should keep the following four steps in mind:

Target expression.

When designing your Phase 0 clinical trial, only select patients that express your target of interest. This process is also referred to as patient stratification. If you do not include patients that express your target, there is a considerable risk of a false negative trial outcome. Namely, your patients lack presence of the target instead the lack of the drug’s efficacy itself.

During the initial phase of target evaluation, you do not want to include patients that don’t express the target in your phase 0 study (such as healthy volunteers). This data will not be representative of your study population who do express the target of interest.

Target validation.

In your selected patient cohort, you should validate the target expression. For example, by histopathology or diagnostic imaging, such as PET/CT imaging. This means selected patients either have to undergo a biopsy or surgery to obtain histopathology or diagnostic imaging data. The retrieved data is used to correlate uptake of your drug to the target expression.

Set realistic recruitment timelines.

When selecting your patient population, you need to consider the feasibility of patient recruitment in numbers and recruitment time. It is important to make sure that you can include the set number of patients within the required timeframe.

Furthermore, you should consider the burden of the clinical trial and the reward for included patients to ensure the drop-out rate is as low as possible. One way to achieve this is to provide patients with realistic information and support. In the end, realistic patient recruitment rates will result in less financial, clinical, and ethical costs of trial extensions or failures.

To do so, you should consider a uni- or multicenter study or even expansion to an international study. Also, awareness of the population in the region from which you will recruit patients (e.g., population demographics, overall disease epidemiology of the region) is of great importance.

Your ethical obligations when selecting a patient population.

Medical Ethical Committee (either regional or (inter-)national) approval is mandatory before you can initiate a clinical study. Furthermore, individual patient informed consent is obligatory and vital to the safe and informed conduct of your clinical trials. This measure assures all precautions have been taken to inform patients of the risks and procedures before they participate in your study.

Furthermore, you need to consider the patient’s current therapy – and possible standard-of-care – before inclusion in your trial. For example, it may be difficult to include patients with a good treatment for a chronic disease who would be required to interrupt an already effective treatment. The (clinical) staff members responsible for the trial should provide inclusion and exclusion criteria that are specific for and sensitive to the population under study. All these considerations should be included in your research protocol that you submit to the research ethics board and approved prior to initiation of the clinical study.

In summary, when you select your patient population you need to consider your target expression, target validation, recruitment timelines and ethical obligations. Only then the outcome of your study can accurately reflect the potential of your tested drug.

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