The Pharmaceutical Development Pipeline: Characteristics of Each Phase

Multiple Steps in Drug Development

Development of a pharmaceutical follows a relatively simple multi-phase pipeline process. Within each of these phases, particular topics are investigated. These include: (Phase I) determining drug safety and dosage in humans, (Phase II) determining if the drug actually treats the disease in humans, (Phase III) evaluates efficacy the drug in large population and is used to gather additional information about how the drug impacts human physiology. With these 3 basic phases, one must also recognize the step of applying for drug approval with regulating authorities and any post-approval research on the drug.

Phases of the Drug Development Pipeline

Phase I: Determine Safety and Dosage in Humans

In Phase I of the pipeline, the investigational ‘new drug’ is administered for the first time to humans. Because this is the first time it is administered to humans, Phase 1 clinical trials usually focus on safety and tolerability of the product and involves only a small number of participants. During this phase, low doses of the experimental medicine are administered and participants are monitored for reactions to the drug. The dose of the new drug is gradually increased during trials to allow the investigator to measure the participant’s response to the drug: whether the drug is sufficiently absorbed, how long it remains in the bloodstream, and which dosage levels are save and tolerated. Phase I investigations usually investigate the new drug with healthy participants although it is often the case that persons with the particular disease that the drug is designed to treat will also participant in the study.

Phase II: Determine if the Drug Treats the Disease

The purpose of Phase II of the pipeline is to evaluate the effectiveness of the experimental drug in treating the illness or medical condition. During this phase, information about the drug’s safety, potential risks, and side-effects are also collected. In this phase, researchers determine the most effective dosages and the most appropriate method of delivering it (e.g., tablets, injections, etc.). Phase 2 clinical trials typically involve more participants than Phase I. Generally Phase II involves between 60 to 300 participants. The participants in this phase are usually patients with a medical condition that the experimental medicine has been designed to treat. Patients are usually identified by physicians at research centers, clinics, and hospitals at multiple sites around the world.

Phase III: Evaluate in Large Population and Gather Additional Information

The purpose of a Phase 3 study is to validate the results of earlier phases against larger populations and gather additional information about the effectiveness and safety of an experimental drug. Studies in this phase generally provide the primary basis for the benefit-risk assessment for the new drug and much of the core information about the drug that is described in the labeling of the medicine. This phase usually involves several hundred to several thousand participants from multiple study sites with many physician investigators. These trials are often randomized and ‘double-blinded’. This means that during each trial, neither the investigator nor the participant know who in the trial are getting the experimental drug versus a placebo or a comparative drug.

Drug Registration

In the Registration stage, the company that wishes to bring a new drug to market files an application with the health regulatory authority of a country in order to obtain approval to market the new medicine in that country. In theU.S., this is filed with the Food and Drug Administration (FDA). In Europe, this if filed with the European Agency for the Evaluation of Medicinal Products (EMEA). If approval of the drug is granted, it can then be sold for use by patients.

Phase IV: Post Market Investigations

In Phase IV trials, researchers investigate the long-term risks, benefits, and optimal use of the drug. Such trials are conducted after the drug has been approved by a regulatory authority in the ‘Registration Stage’.

Drug Development and Evaluation: Examining Brain Function

One of our goals as an organization is to provide pharmaceutical developers with as much information about how their drug affects the human population as possible, as early as possible in the drug development cycle. We have identified Phase II as the most appropriate phase for investigating the effect of a new drug on brain function for multiple reasons. First, in Phase II, the number of participants is suitable for low-cost data acquisition while providing enough data to make statistically driven decisions. Phase II is also early enough in the pipeline that findings can be used to optimize costly Phase III studies, and provide feedback for the creation of new drugs in the molecular development stage.

The method of brain function analysis we use to evaluate the effect of a drug on brain function employs non-invasive electroencephalographic (EEG) data collection. To identify the details of brain function contained in the EEG, we employ our data mining and brain function analysis methodology called MOST-EEG (Multiple Origin Spatio-Temporal – EEG). This methodology allows us to construct detailed system-level models of both the activation of multiple areas of the brain and the coordination of these areas that occurred during the data collection paradigm. This allows us to compare system-level brain function while participants are not receiving the drug and compare it to system-level brain function while participants are receiving the drug.

A more in-depth discussion of the MOST-EEG analysis methodology and how it can be used in pharmaceutical development to understand how the drug impacts brain function and cognition is provided in an article titled, “Creating a Cognitive Model From MOST-EEG Results”. For a discussion of the 'mechanics' of how our organization can help with drug development, see our article titled, " MOST-EEG and Pharmaceutical (1) Development, (2) Re-Purposing, (3) Comparisons: How we help your company with your drug research".