Overview of Clinical Trial Phases

TL:DR - human clinical trials have 4 phases, with the first three being prior to going to market, and the last being a post-release evaluation. Prior to this stage, testing must be conducted in animals and/or human cells and the drug admin must otherwise be satisfied that it’s likely to do what the drug company claims prior to starting phase 1.

This data is taken from an aggregator of clinical trials, CenterWatch. Clinical trials are designed to prove a drugs safety and effectiveness. Most drugs don’t make it, for various reasons - within our community, I can think of a few off the top of my head that never did make it:

  • Cardarine - abandoned due to cancer at high doses
  • RU58841 - abandoned at phase 2 due to the patent running out
  • YK11 - purchased by a competitor and then abandoned

Introduction

Before a drug goes to phase 1, the research must be sent to the FDA (in the US, or the local drug administration for that country) for approval to test in humans. The bar to commence phase 1 trials is understandably high, and generally requires testing on animals and human cells. Once human trials have begun, all side effects are recorded.

Why does that matter? Drugs are tested at a variety of doses to test safety and efficacy. Let’s say you have 100 people trialling Compound X which is effective at 10mg, and trials are testing doses at 1mg, 5mg, 10mg, and 50mg. 10 folks within the 50mg all experience nose bleeds, yet none at 1mg, 5mg, and 10mg experience this effect. This compound is likely to have nose bleeds listed as a side effect, even though it might never be intended to be used at that high of a dose.

Human Clinical Trial Phases

Phases are sequential, with drugs moving from one to the next in order, each stage being approved (or not) by the FDA.

Phase 0:

  • How safe is the drug, at very low doses?
  • Phase 0 trials involve only a small number of volunteers (<15).

Phase 1:

  • How safe is the drug?
  • How is it absorbed, metabolized and excreted?
  • Phase 1 trials involve only a small number of volunteers (20-100).
  • 70% of drugs make it past this phase.

Phase 2:

  • How safe is the drug?
  • How effective is it?
  • Larger sample size, with a control group.
  • 34% of drugs complete this phase.

Phase 3:

  • How safe is the drug? What significant or minor adverse events occur?
  • Lasts several years, involving often thousands of patients
  • Most drugs that make it to phase 3 complete this phase
  • Once complete, FDA can approve to go to market

Phase 4: Post Marketing Surveillance

  • How has it performed?
  • Is it effective long term?
  • Is it cost-effective?

Dive Deep Into Listed Side Effects

As I said in the introduction, I say ‘likely to be listed as a side effect’ because there is variability in how side effects are determined: side effects in clinical trials are frequently assessed in an unstructured fashion, using ascertainment strategies with unclear quality criteria. Therefore when assessing risk and identifying potential side effects of a new compound for a cycle, looking at significant and minor adverse effects as it relates to dose is incredibly important - don’t rely just on what is listed on the side of the bottle or the clinical trial abstract.

Conclusion

Phases of trials can take many years, and like in the case of RU58841 patents may run out before trials are completed. Most of the cost associated with trials is a product of the amount of time required to pass through each phase. Unlike in a lab setting, where an experiment can be easily commenced and finished on set dates, human trials rarely have this luxury. For our purposes, phase 3 trials results are by far the most valuable, though we often make do with phase 2 trials if we even have access to that. Some trial results are also suppressed, presumably due to the potential for folks like us to abuse the compound based on the findings - tren and RU58841 are in this both, neither clinical trials results are available. Certainly, these companies are under no obligation to help us leave humanity behind by making the data easily accessible. Therefore, I’ll take what I can get from them and am grateful for even the limited data that does get released.