Clinical Trials

Patients can be identified for clinical trials either through a physician's referral or by choosing to refer themselves. To determine if someone is a potential candidate for a trial, a high-level review is conducted, looking at the patient's medical history, disease characteristics, any ongoing health conditions, and their willingness to participate. However, this initial identification does not guarantee eligibility or participation in the trial. If a patient expresses interest in learning more or possibly participating, a healthcare professional knowledgeable about the trial will provide a detailed explanation of the trial and discuss the next steps.

It is important to remember that participating in a clinical trial is completely voluntary. All patients should receive compassionate medical care whether they choose to participate in a clinical trial or not.

After a patient is identified and confirms they are ready to move forward, they will begin the screening process. The purpose of the screening process is to make sure that it is safe and medically appropriate for the patient to receive treatment in the clinical trial.

Informed consent

The screening process for clinical trials should always begin with the informed consent process. Informed consent is a crucial step in ensuring patients understand the trial's scope and implications before they agree to participate. Informed consent involves providing detailed information about the clinical trial to the patient, and this process continues throughout the duration of the trial.

Consent forms for clinical trials are often lengthy and it's important to read the entire document. Before signing the consent form, patients must be given the opportunity to thoroughly read the document, have all questions answered by study staff, and have time to discuss the trial fully with family and healthcare providers if desired. The consent form will give information on the following:

• Name of the investigational drug and how it works
• Phase of the trial
• How many patients are planned to be enrolled
• Length of the trial, trial schedule and procedures
• Patient responsibilities
• Potential side effects
• Financial process
• Contact information for the Principal Investigator
• Optional elements of the trial
• Confidentiality aspects

Screening procedures

After signing consent, the next step is to complete screening procedures. Each trial will require different tests at screening. These tests are essential to determine if the trial is suitable for the patient and if the patient is suitable for the trial. Both conditions must be met to proceed, ensuring the trial is appropriate for every participant.

Common screening procedures for MDS trials include the following:

• Bone marrow biopsy and/or aspiration
• Safety labs (routine blood tests)
• Testing for targetable mutations
• Physical exam with a study-associated provider
• Cardiac testing (electrocardiogram/echocardiogram)
• Review of current medications and medical history
• Collection of optional samples (typically for future research)
• Questionnaires about quality of life
• Scans (often if iron overload is suspected)

After the screening tests are completed, study personnel compile an eligibility packet that details the criteria patients must meet to participate in the trial. This packet is then completed by the clinical trial site and submitted to the trial's sponsor or the drug company for final approval and sign-off. This process ensures that all potential participants meet the requirements to maintain the safety and integrity of the clinical trial.

Once a patient qualifies for participation, they will be scheduled to start treatment in the clinical trial. Some investigational medications are administered in the hospital, while others are given in a clinic. The location for administering the medication is determined by factors such as the medication's safety profile, the level of monitoring needed, and the number of study procedures required. Some treatments can be in pill or tablet form, allowing patients to take them at home on designated days.

Study personnel will explain all aspects of the treatment, including how and when the medication should be administered (called the administration schedule) and how to properly store it prior to the patient receiving the first dose. Patients should also receive contact information for any concerns that may arise after hours or over the weekend. All necessary paperwork, such as pill diaries, questionnaires, and forms for financial reimbursement, will be discussed and provided to the patient. Additionally, insurance approvals will be secured before treatment begins.

Every clinical trial has a different schedule of assessments. Often the first couple months on a trial are the busiest. During this period, patients usually have more frequent visits with their healthcare provider and more study samples will need to be collected.

Since the investigational drug is undergoing evaluation and hasn't received FDA approval for the specific condition being studied, it is crucial to closely monitor its levels in the body. This monitoring typically involves conducting blood tests to measure the concentration of the drug at set timepoints. These blood tests help researchers understand how much of the drug is absorbed, how the body processes it, and how long it remains within the body. To achieve this, pharmacokinetic and pharmacodynamic tests are conducted. Pharmacokinetic tests track the drug's movement through the body - specifically, its absorption, distribution, metabolism, and excretion. Pharmacodynamic tests focus on the drug's effects on the body, as well as how the body's biological responses affect the drug's performance.

Other necessary procedures like checking vital signs, lab tests, and electrocardiograms are performed on a strict schedule during clinical trials. Maintaining consistency in these procedures is crucial for obtaining reliable data, which is essential for the FDA approval process.

While participating in a clinical trial, patients are closely monitored for any potential side effects and their response to the therapy. It is very important for patients to be open and honest with the healthcare providers about how they are feeling and how they believe they are tolerating the investigational drug.

It is important to note that patients can withdraw from (choose to leave) a clinical trial at any point, without giving a reason. This decision will not impact their ongoing care or treatment.

Treatment on a clinical trial will continue until one of the following occurs:

• The patient completes the trial period as defined by the protocol
• The patient experiences a side effect that cannot be managed
• It is determined that the patient is not responding to the trial therapy
• The trial is ended by the sponsor for safety reasons
• The patient chooses to end participation in the trial for any reason
• The patient demonstrates a pattern of non-compliance which could impact data and safety
• A new therapy becomes available which is a better option for the patient

After a patient concludes their participation in a clinical trial, an end-of-treatment visit is scheduled. The purpose of this visit is to identify any ongoing side effects and to develop an appropriate follow-up schedule. Most trials require patients to return for a safety evaluation about 30-90 days after their last dose of the study drug. Should any side effects continue beyond this period, further follow-up appointments may be required to address and resolve these ongoing issues.

Clinical trial follow-up also encompasses a long-term follow-up period. During the long-term follow-up, patients are periodically contacted to review the current treatments they are receiving and to assess their disease status. Patients can opt out of the follow-up phase; however, the long-term data that is collected really helps to develop a comprehensive side effect profile of the trial medication.

Typically, it takes several years for a clinical trial to conclude fully. All published data from the trial is made available on www.clinicaltrials.gov.