eIND: exploratory IND versus emergency IND

eIND may be referred to as either exploratory Investigational New Drug (IND) or emergency Investigational New Drug (IND). An "Exploratory IND" and an "Emergency IND" are both regulatory mechanisms used in the United States by the Food and Drug Administration (FDA) to allow for the use of investigational drugs in certain circumstances. It's important to note that the exploratory IND and emergency IND represent distinct concepts.

Exploratory IND (eIND):

exploratory IND may be called 'Phase 0' clinical trial. Exploratory IND was described in FDA Guidance for Industry, Investigators, and Reviewers "Exploratory IND Studies". The guidance defined the exploratory IND as the following:

Purpose: Used for early-stage clinical trials to explore the preliminary pharmacokinetics and the pharmacodynamics features, not the safety and efficacy of a new drug or treatment. The dose is sub-therapeutic level or micro-dose.

Timing: Typically used in the early stages of drug development, before a drug has been extensively studied in humans and before the phase 1 study

Process: Requires submission of an IND application to the FDA, detailing the proposed clinical trial protocol, preclinical data, and any available safety information. However, less pre-clinical data or animal data is required for the eIND study than for the typical phase 1 study.

Review: The FDA reviews the eIND application and provides feedback before the trial can proceed.

Requirements: Investigators must adhere strictly to the protocol outlined in the IND application, and any deviations must be reported to the FDA.

Emergency IND (eIND):

Emergency Use Investigational New Drug (IND) applications are part of expanded access program (also referred to as compassionate use). expanded access program was described in 21 CRF Part 312 "Subpart I—Expanded Access to Investigational Drugs for Treatment Use". FDA has a designated page to describe the "Expanded Access" process. 

emergency INDs may also be called single-patient INDs, Individual Patient Expanded Access, or Single Patient Expanded Access. They are initiated in urgent scenarios where immediate access to an unapproved drug is necessary, and the clinical circumstances do not permit the time required for a standard IND submission. emergency INDs are primarily utilized in cases of life-threatening conditions where no established treatment options are available.

21 CRF Part 312.310 described the process for expanded access for individual patients, including for emergency use. 

Purpose: Used in emergency situations where there is no alternative treatment available, and the patient's condition is serious or life-threatening.

Timing: Typically used when there is an urgent need to provide access to an investigational drug outside of a clinical trial setting.

Conditions: Reserved for cases where standard treatments have failed, are unavailable, or are not suitable for the patient.

Review: The FDA still needs to review the emergency IND application, but needs to provide feedback / approval in a very short period (hours/days).

Phased Clinical Trials - Phases 0, 1, 2, 3, 4

Clinical development programs for drugs and biological products include phased clinical trials ranging from Phase 0, 1, 2, 3, and 4.  Phase 0 study is not typically needed. Phases 1, 2, and 3 studies are typical pre-market clinical trials and Phase 4 studies are post-market clinical trials. There are a lot of articles and books discussing the clinical trial phases. I borrowed some illustrations/slides from FDA's 'Clinical Research Phase Studies" and other web resources:

Phase 0 Clinical Trials:

• Phase 0 trials, also known as exploratory or pre-phase I trials, involve a small number of participants (usually fewer than 15) and are conducted very early in the drug development process.
• The primary goal of Phase 0 trials is to gather preliminary data on how the drug behaves in the human body, including its pharmacokinetics (how the drug is absorbed, distributed, metabolized, and excreted).
• These trials may involve administering subtherapeutic doses of the drug to minimize risks to participants while still providing valuable insight

Phase 1 Clinical Trials:

• Phase 1 trials are the first stage of testing in humans and typically involve a small number of healthy volunteers (or sometimes patients with the target condition).
• The main objectives of Phase 1 trials are to evaluate the safety and tolerability of the drug, determine its pharmacokinetics and pharmacodynamics, and establish an initial dose range for further testing.
• These trials are designed to identify any potential adverse effects and to determine the most appropriate dosage for subsequent studies.
  

Phase 2 Clinical Trials:

• Phase 2 trials involve a larger group of patients (typically several hundred) who have the condition or disease that the drug is intended to treat.
• The primary objectives of Phase 2 trials are to further assess the safety and efficacy of the drug, explore different dosages and dosing regimens, and gather preliminary data on the drug's effectiveness in treating the target condition.
• These trials help to provide more information about the drug's potential benefits and risks and inform the design of larger, more definitive Phase 3 trials

Phase 3 Clinical Trials:

• Phase 3 trials are large-scale studies that involve hundreds to thousands of patients and are designed to provide definitive evidence of the drug's safety and efficacy.
• The main goals of Phase 3 trials are to confirm the effectiveness of the drug in treating the target condition, further evaluate its safety profile, and compare it to existing treatments or placebo.
• Phase 3 trials are crucial for obtaining regulatory approval from health authorities such as the FDA (Food and Drug Administration) in the United States or the EMA (European Medicines Agency) in Europe.

Phase 4 Clinical Trials:

• Phase 4 trials, also known as post-marketing surveillance trials or post-approval studies, are conducted after a drug has been approved for marketing and made available to the general population.
• These trials continue to monitor the drug's safety and effectiveness in real-world settings, identify any rare or long-term adverse effects, and gather additional information about its optimal use.
• Phase 4 trials play a critical role in ensuring the ongoing safety and efficacy of medications after they have been approved for widespread use.

Overall, phased clinical trials are an essential part of the drug development process, providing valuable data at each stage to inform decision-making and ultimately bring safe and effective treatments to patients.