What Are Clinical Trials?

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Contents

Introduction

Biologic Development

Clinical Trial Phases

Ethics

Government Requirements

Why Volunteer?

Risks

Every household medicine, surgery, cancer therapy, diabetes drug, vaccine, intervention, or treatment, that can be prescribed has to be tested and approved before the government legalizes its use in medical practice.

A clinical trial is a long-term experiment to develop a new medical treatment that could save or change lives. Every step is a measurement of safety and effectiveness to see if the treatment is worth the massive investment it takes to create.

This is how almost every medical procedure and medicine you’ve ever heard of has been tested. Clinical research and the people who practice it contribute to the world in saving lives, and in the reduction of disease and illness in the world.

Human volunteers receive the treatment under close medical supervision and strict rules from the government. Due to the history and nature of performing research on humans, clinical trials are led with intentionally high levels of ethical decision making. Scientists must respect the rights of the volunteers and practice compassion at all times to avoid causing harm while conducting research.

Typically, a drug development company will hire a medical center to test the drug with trials. To increase the speed of testing a large number of people, the developer may include many medical centers. All of the trial findings are reported and analyzed by the developer, and if enough testing shows that the drug can help people safely, the developer will submit an application to the government department for approval.

It is a long process. From the initial idea for a treatment, to its eventual approval for prescription and use, development can take up to a decade or more. Drug companies have to fund extensive and expensive research, just for the chance that their treatment will have a massive impact and pay the investment back.

Scientists uncover how illness begins and develops. They devise a molecular approach to preventing or controlling it; and they collect data that improves our future understanding of medical science and diseases.

Phases of Clinical Trials

The process for receiving regulatory approval is centred around administering the treatment under strict scientific guidelines and then collecting and analyzing data related to the outcomes of administering the treatment.

There are 5, and sometimes 6 phases of clinical trials.

The advantage of breaking down every step into phases is to provide better control over things like the quality of lab work, the quality of patient care, leading with ethics, and receiving informed consent. Each of these critical tasks for trial coordinators risks serious harm if they are not performed to high standards.

Preclinical Testing

During all phases of testing the focus remains on evaluating the safety, and effectiveness, of the treatment.

Before testing on humans, scientists perform lab experiments using simulations and artificial intelligence (A.I.) to examine molecular data for insights. Only the best molecular composition is chosen and animal testing begins.

Animal testing is the first real use of the new biologic, and can reveal information about how a living organism handles and responds to receiving it. There is a possibility the biologic is toxic. Scientists examine the pharmacokinetics, and gain deep knowledge of how it works within the body.

Scientists want to discover that the drug causes no or little side effects, and that it does have the intended effect on the body. Once enough data has been collected showing that the biologic doesn’t appear likely to hurt people, testing can move to phase one.  

When researchers are ready to move into phase 1 of clinical trials, they must submit an Investigational New Drug (IND) application. This declares their plan for investigation, including: the study protocols, chemistry information, manufacturing planning and data, and regulations, pharmacology data, as well as any human experience data and other relevant information.

The use of A.I. in preclinical planning is rapidly evolving and allows for some prediction into the effectiveness and safety of a given molecule so new treatments have better biological tuning out of the gate. That’s time, money, and hardship, all being avoided.

Phase I

In Phase I it is expected that there will be less side-effects because of extensive pre-testing, but humans are biologically quite different from animals. Phase I involves gathering tolerance data primarily, and treatment strength data second.

Roughly 20-100 compensated volunteers participate in Phase I, helping doctors determine the maximum dose before any significant side-effects.

Volunteers experience frequent blood draws to assess pharmacology, and are monitored by clinical trial doctors.

70% of biologics progress beyond this.

We do not do Phase I trials. Most of our trials are Phase II and III.

Phase I

Similar to phase I the primary focus is dosage, safety, and effectiveness. The focus is determining the best dosing, and seeing how well it can actively reduce symptoms.

Most phase 2 trials are randomized and placebo controlled. Neither doctor or patient know who receives the placebos. This is needed, because people can “feel better” because they believe in the medicine. This can cause patients to report optimistic or unrealistic results which ruins the scientific integrity of the study.  

In this phase, around 100-500 participants help doctors search for rare side effects and explore how it performs in diverse groups of people. Knowing about how the drug interacts with a larger population helps develop confidence in its safety.

Phase III

It can take four to five years to reach phase 3. If a treatment reaches phase III it is typically doing very well in clinical trials. Trial rules are strictly monitored by professionals, and any testing that fails to uphold standards of safety or integrity; or that does not produce a significant reduction of symptoms may be cancelled.

This part of the study aims to expand testing to a large and diverse pool of participants. Treatments work differently for people depending on gender, age, race, sex, ethnicity, and so on; and so phase 3 is often conducted across multiple research sites.

Between 500-2000 participants volunteer to develop certainty that drug is safe to prescribe for patients. If everything goes well in this phase the developer will apply for regulatory approval.

Phase IV

After the drug is approved by government regulators such as Health Canada, or the Food and Drug Administration (F.D.A), doctors can begin prescribing it to patients. However, research doesn’t stop here.

Previous to approval, doctors administer the drug. Now the patient can go and see a pharmacist to pick it up for themselves.

As the drug is more freely distributed, Phase IV research begins.

Usage is closely monitored for safety and continues for many years to verify real world safety information.

Much of the knowledge we gain on new drugs is acquired after approval, and many approved drugs become targets to treat diseases that were not originally their intent.

Ethics In Clinical Trials

Clinical trials can’t happen without brave volunteers who believe in our vision.

Because volunteers are placed in a vulnerable position as trial participants and the potential for side-effects, trial coordinators must have respect for and be trained in a long code of ethics. Upholding ethical rules and codes means being transparent about safety, committed to honesty, and protecting volunteers from all preventable harm.

The United States National Institute of Health references several important guideline documents on ethics in clinical research:

Nuremberg Code (1947)
Declaration of Helsinki (2000)
Belmont Report (1979)
CIOMS (2002)
U.S. Common Rule (1991)

These codes lay out rules such as informed consent, and limiting the harm that can be caused to volunteers in trials. Much of their content is a response to past violations, in particular by the Nazis during World War two. In the interest of historic fairness the United States has also been guilty of highly unethical clinical trial practice, though not quite as horrific.   The general idea is that patients should be protected, reasonably safe from harm, and capable of withdrawing at their wishes.

Patients should also be fully informed of what risks the trial entails. Trials must be run with adequate preparation and with carefully considered intent so that the research answers a question which is expected to benefit society. Government regulations have become tighter since the first rules for clinical research were published, providing a safer and more stringent clinical trial process.

Regulatory Oversight

In Canada clinical research is overseen by Health Canada. Health Canada conducts inspections to ensure that clinical trials are following all ethical and legal standards in recruitment, and trial practices. Before a clinical trial can begin, it must apply to receive Health Canada’s Approval   There are also many internal review boards (IRBs) that examine the administration of clinical trials. All of our patient facing material must first be approved by the sponsor of the drug, and secondly by an IRB to ensure adherence to legal requirements.  In the United States clinical research oversight is provided by the Food and Drug Administration (FDA).

Why do people participate in clinical trials?

Helping researchers develop better treatments for everyone.

Contributing to medical understanding of diseases for future generations.

Potential to gain access to treatments that could relieve symptoms.

Are there risks associated with clinical trials?

Yes. This is why researchers pursue high ethical and scientific standards in every step of the clinical trial process to avoid wasting time or money, or much worse, such as lying to, or hurting people. Clinical administrators should have strong moral awareness and be willing to fight for what’s right for volunteers.

Any medication or intervention that’s in a clinical trial is being tested for its safety first and foremost. Pre-clinical and Phase I testing is on exceptionally high alert for side-effects. Usually by the start of phase 2, it’s been tested on 20-100 people, and has been determined to have a “low” likelihood of being dangerous.

The medication may cause uncomfortable side effects, and in some cases they may be serious. The investigational drug may simply not work for you, or might not work that well. Also, you could be selected to be a part of the placebo group and no one would know; then you might consider the trial a waste of time.

The benefits of clinical research must be weighed against the risks. With the help of brave volunteers who believe in clinical trials we can provide drugs for far more diseases that work either more safely, more powerfully, more conveniently, or even sometimes all at once. And when we can change lives by selectively researching and treating diseases that is an incredible achievement for everyone.

SimcoDerm is a full service, comprehensive dermatology clinic located in Barrie. We provide our services to all the patients in Simcoe County and beyond.

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