The Clinical Trial Process For Psychedelics And Beyond, Explained

This article was originally published on Microdose Psychedelic Insights and appears here with permission.

Rarely has there been an investment community so focused on science. Normally concerned with market closings and earnings calls – suddenly we have investors around the world waiting for Phase 2A clinical trial results with bated breath. While many other biotech and pharmaceutical stocks are also heavily dependent on drug development, they’ll often have products already in the market, thus splitting investor’s attention between the lab and current sales.

Yet with psychedelic medicines, we have a buzzing new industry and investment community – Reddit groups and all – almost entirely focused on the drug development process.

But what’s an “IND”? What’s the difference between Phase 2A and 2B? And what are the odds of a drug actually making it through trials and into the market?

Here’s a little primer to help you with the lingo and better follow your favorite up-and-coming molecule.

Regulatory agencies are here to help

Getting a new drug to market is a long and rigorous process. Regulatory entities like the FDA and Health Canada have created a system of progressive stages, each designed to run candidate drugs through established scientific measures to ensure they are safe and effective.

Focusing on the FDA for now (as they are the agency the majority of public companies begin their drug applications with), firms seeking to get their drug approved by the FDA for commercial sales need to complete five steps: discovery & development, preclinical research, clinical research, review, and post-market safety monitoring.

The early stages (discovery & development) are a time of both innovative thinking and strict standards. Fresh insights into how a disease works, or novel ways of using a compound, can inspire ideas for new treatment methods. Companies theorize on new ways to treat conditions, using both new and existing molecules (think psychedelic medicine R&D).

Most of this is done in test tubes, confirming that it meets minimum standards for safety and potential efficacy. Once a promising compound is identified (and only a tiny percentage of candidates make it out of this development stage) it’s time to move onto the big leagues – submission for pre-clinical and clinical trials.

The clinical trial process: the ultimate road to FDA approval

Success in clinical trials is the number one factor in determining the long-term viability of a biotech stock. The psychedelic medicine space will be focused on trial results for the next several years, so here’s a breakdown of the approval process.

Preclinical

Before a drug can be tested on humans it must be proven safe and non-toxic. This work is done in the lab and with animal testing, with tests engineered to the specific compound in question and with the proposed future human trials in mind. Everything here is aimed at getting approval for human trials, so researchers often gather data from past trials, combine them with their new results, and prepare a submission called an IND.

The IND, or Investigational New Drug Application, gives details of the drug’s preclinical safety results, chemistry, dosage, manufacturing, and plans for human testing in trials. The FDA then reviews the IND to ensure clinical trials will be safe for humans. If approved, the candidate compound can then move onto actual clinical trials—the first real step to getting a product to market.

But beware, only one in 1000 compounds that enter laboratory testing ever make it to human trials.

Phase 1

This round of clinical trials is focused primarily on safety. The candidate drug is given to healthy patients, usually with gradual dose increases, with the goal of tracking possible side effects and gauging proper dosing levels.

These trials generally have a smaller number of participants, between 20 to 100. With basic efficacy results already gathered in preclinical, the main point here is to evaluate the overall safety and predict the safest dosage.

Here the odds are much better with approx 70% of drugs moving to the next phase.

Phase 2

After safety and appropriate dosing have been established, the clinical trial can graduate to Phase 2. The proposed compound is tested on a larger group of people (from a few dozen to a few hundred) and the group will have the condition the drug is attempting to treat.

Here the move is from safety to both efficacy and safety. The trial is randomized, with some receiving the drug and others a placebo. This stage can run for up to 2 years and there’s a 30% of successful completion.

Phase 3

This is the big one. The final major step before drug approval. Here the candidate works with the FDA to design a trial that assesses the drug’s efficacy and monitors for adverse effects. Here the focus is if it works on a larger population size, with groups ranging from hundreds to thousands of patients.

Since this is the final crack at human trials, the group is made as diverse as possible across age, gender and race, with monitoring for correct dosage and long-term side effects.

The length of this phase can be 1 to 3 years and the success rate is 25-30%.

And finally onto the market and (hopefully) to the moon

So these are the main steps of the drug approval process. After successful completion of Phase 3, there is an NDA submission (New Drug Application) that contains all trial results and that the FDA uses for final approval.

Once on the market and making millions, the drug can also go through a Phase 4 trial that looks at post-sale consumption in real-world settings, hoping to identify long-term effectiveness and safety issues.

For approval in other countries, there are international agencies like the ICH-GCP (The International Conference on Harmonization-Good Clinical Practice) that standardize clinical trial practices across nations, allowing results from trials to be used for submission to other regulators like Health Canada.