Clinical trial

Clinical Trials: An Overview

What is a Clinical Trial?

A clinical trial is a systematic investigation in human subjects to evaluate the safety and efficacy of a new drug. It is an essential step in medical research to generate data on health interventions before they become publicly available.

Key points:

• A structured process to test new drugs or treatments in human subjects.
• Ensures that new treatments are safe and effective before market approval.
• Supports the development and introduction of new drugs to the market.

---

What is a New Drug?

A new drug refers to a pharmaceutical product that:

• Has not been extensively used within the country.
• Has not received safety and efficacy approval from the Central Licensing Authority (CLA), such as the Drug Controller General of India (DCGI).
• Includes active pharmaceutical ingredients, phytopharmaceutical substances, and modified versions of existing drugs (e.g., changes in dosage, administration route, or formulation).
• Covers modified or sustained-release formulations, novel drug delivery systems, vaccines, monoclonal antibodies, gene therapies, and stem cell-derived products.

---

Drug Review Steps for Clinical Trials

The drug review and approval process is regulated by agencies such as the USFDA, EMA, and CDSCO and includes the following key steps:

1. Preclinical Testing – Animal testing to assess toxicity and pharmacological effects.
2. Investigational New Drug (IND) Application – A formal request to regulatory authorities for human testing.
3. Clinical Trials (Phases 1-3) – Progressive testing in human subjects.
4. New Drug Application (NDA) Submission – A formal request for drug approval and market release.
5. Regulatory Review – The FDA reviews and determines whether the drug is approved, approvable, or not approvable.
6. Phase 4 (Post-Market Studies) – Ongoing surveillance after the drug is marketed.

---

Phases of Clinical Trials

Phase	Purpose	Key Characteristics
Phase 0	Exploratory	Very small-scale study with limited human exposure; evaluates pharmacokinetics and pharmacodynamics.
Phase I	Safety & Dosage	Small group (20-100 participants); assesses safety and dosage range.
Phase II	Efficacy & Side Effects	Medium-sized group (100-300 participants); evaluates drug effectiveness and monitors side effects.
Phase III	Confirmatory	Large group (1,000-3,000 participants); compares the new treatment with standard treatments.
Phase IV	Post-Market Surveillance	Conducted after approval to monitor long-term safety and real-world effectiveness.

---

What is a Bioavailability and Bioequivalence (BA/BE) Study?

• Bioavailability Study: Assesses the rate and extent to which a drug is absorbed and reaches systemic circulation or the target site.
• Bioequivalence Study: Determines whether a generic drug has the same rate and extent of absorption as the reference drug when administered in the same molar dose under similar conditions.

---

What is DSUR (Development Safety Update Report)?

A DSUR is a periodic report submitted to regulatory authorities, such as the FDA or EMA, to ensure drug safety during clinical development.

Key functions:

• Summarizes safety findings from clinical trials and post-marketing surveillance.
• Assesses the benefit-risk profile based on adverse events and safety data.
• Ensures patient safety and makes recommendations for necessary regulatory changes.

---

What is an Interventional Study?

An interventional study is a clinical research study in which participants are assigned to different treatment groups to evaluate the effects of interventions on biomedical or health-related outcomes.

Key points:

• Assignments are determined by the study protocol.
• Participants receive diagnostic, therapeutic, or other medical interventions.

---

Procedure for Conducting a Clinical Trial

Conducting a clinical trial is a complex and highly regulated process, involving multiple steps:

1. Study Design & Protocol Development – Defining objectives, methodology, and endpoints.
2. Regulatory Approvals – Obtaining necessary permissions from agencies like CDSCO, USFDA, or EMA.
3. Ethical Review – Review by an Institutional Ethics Committee (IEC) to ensure participant safety.
4. Recruitment & Informed Consent – Selecting participants and obtaining their consent.
5. Randomization & Blinding – Randomly assigning participants to treatment/control groups to reduce bias.
6. Intervention & Data Collection – Administering the drug and collecting safety and efficacy data.
7. Data Management & Analysis – Organizing, analyzing, and interpreting study data.
8. Safety Monitoring – Monitoring adverse effects throughout the trial.
9. Trial Completion & Reporting – Concluding the study and submitting results to regulatory authorities.