From Phase 1 to Phase 3... How Do the Confusing Clinical Trials Differ? [BioNOW]

A researcher is focusing on COVID-19 treatment research at the Central Research Institute of Enzychem Lifesciences in Jecheon, Chungbuk. Photo by Jinhyung Kang aymsdream@

[Asia Economy Reporter Lee Chun-hee] The COVID-19 pandemic has sparked increased interest not only in COVID-19 vaccines and treatments but also in the development of various new drugs. However, developing new drugs requires going through a lengthy process.

Typically, the core of the new drug development process is the 'clinical trial.' Only after confirming efficacy and safety through clinical trials can a drug be used in actual patients. Efficacy simply means the drug's effectiveness. COVID-19 vaccines or treatments must prevent COVID-19 or improve the condition faster than natural recovery, and diabetes medications must demonstrate effects such as lowering blood sugar through clinical trials. Safety means the absence of fatal side effects. For example, if a prostate treatment drug causes hair growth, that might be acceptable, but if it induces heart attacks, it would be difficult for the drug to receive approval.

Recently, with COVID-19 vaccines and treatments being developed in less than two years, many people think clinical trials finish within 2 to 3 years. However, the usual clinical process takes about 10 years. Phase 1 takes 1 to 2 years, Phase 2 takes 2 to 3 years, and Phase 3 takes about 4 years.

Even if a new drug candidate is discovered, most fail to confirm efficacy and safety during clinical trials and are eliminated. Many companies disclose clinical trial information with cautionary notes such as "The probability of a clinical trial drug receiving final approval as a pharmaceutical product is statistically known to be about 10%," and "Results that do not meet expectations may occur during clinical trials and approval processes, and accordingly, the company may change or abandon commercialization plans." In reality, passing each clinical phase is a significant achievement for companies, but many cases end with development being halted due to failure to overcome clinical hurdles in the new drug development market.

Phase 1=Safety · Phase 2=Efficacy · Phase 3=Final Verification

Clinical Phase 1 trials for the development of a COVID-19 vaccine are being conducted in Seattle, USA. [Image source=Yonhap News]

So, what are the differences between each clinical phase? The biggest difference lies in the purpose of each phase. Accordingly, detailed methods and the number of participants also vary.

First, Phase 1 is the process of testing the safety of the drug. Although the drug is developed to treat a disease, it might cause other diseases when administered to the human body, so this is tested. It is conducted on a small group of healthy individuals, typically between 20 and fewer than 100 people. Only healthy adult volunteers who meet strict criteria such as age, body mass index, alcohol consumption status, and medical history can participate in Phase 1. The goal is to determine whether there are any major side effects when the drug is administered and to understand the degree of drug absorption.

However, as an exception, Phase 1 trials for anticancer drugs may be conducted on patients who are the intended recipients of the treatment. Since the disease may be life-threatening without immediate treatment, even if the drug causes other side effects, it may be administered to patients if it is judged acceptable.

If no toxicity is found when administered to healthy individuals in Phase 1, Phase 2 confirms whether the new drug actually has the efficacy to treat the targeted disease. It assesses whether the drug works properly in the body and how much improvement it brings. Often, different dosages are administered during this phase. Phase 2 also includes the process of finding the optimal dose that maximizes efficacy while minimizing or avoiding side effects.

Administration of the clinical trial phase 3 for SK Bioscience's COVID-19 vaccine candidate 'GBP510' is underway. (Photo by SK Bioscience)

For this purpose, from Phase 2 onwards, 100 to 300 patients suffering from the target indication are recruited for the trial. However, not all of them receive the new drug. To verify the drug's effectiveness, comparisons are made between the group receiving the new drug and a control group receiving a placebo (such as saline injections or vitamins).

In actual clinical trials, neither the participants nor the medical staff conducting the trial know whether the patient is receiving the new drug or the placebo. This is to prevent distortion of results caused by the 'placebo effect' or 'nocebo effect.' The placebo effect is well-known: patients experience symptom improvement because they believe the drug is effective, even though it has no actual effect. If the placebo effect occurs in the treatment group, the drug's efficacy may appear exaggerated or falsely positive. The nocebo effect is the opposite, where patients believe the drug causes side effects, which may cause side effects to appear or be exaggerated even if none exist. To avoid bias, both patients and doctors are blinded to the treatment allocation in a 'double-blind' trial.

Typically, product approval is based on Phase 3 results rather than Phase 2, but approval can be granted at this stage as well. Conditional approval or emergency use authorization applies in such cases, especially when urgency is recognized, as during the recent COVID-19 pandemic. However, since it is conditional, a large-scale Phase 3 trial is still required for formal approval.

The final Phase 3 is conducted on a large scale, usually involving about 1,000 to 5,000 participants. It verifies whether the dosage and administration confirmed in Phase 2 are truly meaningful and thoroughly examines the drug's effects in the body. Phase 3 trials often take place in multiple countries, not just one, because drug efficacy and side effects can vary by race, such as Asian, Caucasian, or African descent, as well as by age and gender. Due to the global scale, the costs are enormous. It is said that about 70% of the total new drug development cost is spent on Phase 3 trials.

This content was produced with the assistance of AI translation services.