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Ask The Expert: How Do Clinical Studies Work?

Written by C. Fookes, BPharm on Aug 18, 2017.

What Is A Clinical Study?

You might have seen an advertisement in your news feed recruiting volunteers for a clinical study. Maybe somebody close to you has been asked to participate in a clinical trial that is testing a new treatment. Or perhaps you are really broke and have been thinking about putting yourself forward for clinical research to earn some extra cash.

The aim of most clinical studies is to assess how safe or effective a new medicine, device, or non-drug treatment is. Generally, people enroll in clinical studies for financial reasons or because they have the condition being studied and they want to help find a better treatment for it. But before you put your body on the line for science, there are a few things you need to know.

Clinical Studies Assess Safety And Efficacy In Humans

Clinical studies are a formalized, structured way to document how humans respond to a particular intervention and provide vital information that can be referred to time and time again. Typically, preliminary safety or efficacy research regarding the treatment in question would have already been carried out in animals. But because animals are quite different to humans in the way they absorb, metabolize and eliminate drugs, every drug or procedure needs to undergo some form of human testing before it is made available for widespread use.

The majority of clinical studies focus on one particular outcome or related outcomes, for example:

  • Natural history: the natural progression of a disease or health condition
  • Prevention: how to prevent a disease from occurring in people who have never had the disease or from recurring in those who have already had it
  • Screening: how best to detect a certain disease or health condition preferably before symptoms develop
  • Diagnosis: determining the best test or procedure for diagnosing a particular disease or condition
  • Treatment: evaluating which drug, combination of drugs, type of surgery or radiation therapy works the best in a particular disease or condition
  • Quality of life: deciding which intervention makes the most difference to a person's comfort and well-being.

First Things First: Informing The FDA

Before a new treatment even goes near a human, drug companies or sponsors must submit an Investigational New Drug (IND) application to the FDA. This IND must include:

  • Particulars about the side effects reported in animals, especially any that caused great harm
  • Specifics of the manufacturing process
  • Details about future studies to be conducted (clinical protocols)
  • Historical data from any prior human research
  • and information about the investigator.

All Clinical Research Needs A Plan And Funding

All clinical research is conducted according to a plan - this is known as a protocol. The protocol describes who can participate in the trial, the intervention involved, the duration of the study, and what outcomes will be measured. A protocol also states what steps the investigational team will take to safeguard the health of all participants.

The Institutional Review Board (IRB) is an independent committee of physicians, statisticians, and lay people that monitor the majority of clinical trials in the U.S. to ensure that the risks involved in participating in any trial are worth any potential benefits. They also make sure the trial is ethical and ensure the rights of participants are protected.

Clinical trials are notoriously expensive, with the average cost of bringing a new drug to market estimated to be over a billion dollars. Funding typically comes from pharmaceutical companies, medical institutions, voluntary groups, physicians, organizations or individuals. Sometimes federal agencies such as the National Institutes of Health or the Department of Veterans Affairs foot the bill. Whoever funds the research is called the sponsor.

Different Types Of Clinical Study: Observational Studies

Clinical studies can be broadly classified into observational studies and clinical trials.

Observational studies tend to be passive in their approach. They do not randomly assign a specific intervention to people in a predetermined way, rather they just observe how people respond to an intervention that has been determined by a doctor to be the most appropriate for them. The main problem with observational studies is bias. Both the patient and the investigator know what treatment has been assigned, which can influence the way they report subjective outcomes. For example, an observational study may record how older adults rate their pain levels after acupuncture for back pain.

Examples of observational studies include:

  • Case studies or case series: These follow the clinical course of one individual or a group of individuals with a particular condition
  • Cross-sectional studies: These may involve chart reviews or surveys which look for certain exposures and match them with certain outcomes
  • Case-control studies: These include people with a particular condition or outcome of interest with people who do not have the condition or outcome (these people are called the controls). These type of studies are always retrospective because they look back and assess exposure to a certain risk factor
  • Database studies: These review data from a patient registry and look at exposures and outcomes
  • Cohort studies: These are usually forward-looking studies that take a specific group of people or a section of the population and report events that occur from that point on.

Different Types Of Clinical Study: Clinical trials

Clinical trials are more proactive in their approach. These type of trials aim to determine the outcome of a specific predetermined intervention, which may be a drug, a device, a procedure, or a lifestyle change, such as diet or exercise.

Comparative clinical trials, also known as controlled clinical trials, compare a new intervention with one that is already available, or try to determine which of the currently available interventions is the most effective. Some comparative trials may be tasked with determining the most effective dosage for a particular condition, or assessing the risk of side effects associated with that particular intervention. Typically, one group of patients receives the intervention, while another receives the standard or current treatment or a placebo (a placebo is a substance or treatment with no therapeutic effect).

The best quality comparative studies are those that are double-blind (which means that neither the doctor nor the patient knows what intervention is assigned) and randomized (where the patients are assigned to a particular intervention by chance).

Phase I, II, and III Trials

Clinical trials may be designated as phase I, phase II, phase III, or phase IV (also called postmarket research).

Phase I studies aim to determine the optimum dosage range of a particular drug and what side effects are likely. Phase I trials usually last no longer than a couple of months and are conducted in 20-100 healthy volunteers or people with the disease/condition. Approximately 70% of drugs move from phase I studies to phase II testing.

Determining a treatment's effectiveness is the main purpose of phase II and III trials. Phase II trials are conducted in several hundred people with the disease/condition over several months to 2 years. Side effects are also recorded, and by the time a drug has reached the end of phase III testing, investigators will have a fairly good idea of what percentage of people will benefit from the treatment and how many are expected to develop side effects.

Only 7% of all treatments that enter phase I testing finish phase III. This is usually the time a treatment is taken to market, and research conducted after this time is usually called postmarketing research, or sometimes phase IV research. Trials that are done once a treatment is in widespread use ofter uncover previously unknown or rare adverse reactions because thousands of people who are taking the treatment are now being monitored.

Weighing Up The Risks Vs Benefits Of Participating In A Clinical Trial

If you are thinking about participating, or have been asked to participate, in a clinical trial, you need to weigh up the risks and benefits FOR YOU!

The lower the phase of the trial, the riskier it is. Phase I trials are concerned with determining dosage and discovering side effects, so chances are some treatments may have side effects or harms that the investigators don't know about. By the time a drug has reached phase III, the developers have a pretty good idea of how effective it actually is and the most common side effects to expect.

Although it is rare for somebody to be seriously injured or die of complications resulting from participation in a clinical trial, it can happen. Complications that require medical attention are not uncommon; however, the majority of people typically only experience minor, short-lasting side effects. Before participating in a trial you will be asked to sign an informed consent document which outlines all the known risks.

Informed Consent: Make Sure You Understand All The Risks And Benefits

Before you sign anything, make sure you have been provided with all the information you need to know about the study - such as its purpose, duration, risks, potential benefits, required investigations or procedures, and the contact details of the investigators.

If you are having difficulty understanding the information, ask somebody. Members of the research team can help break down certain aspects of the study to make it easier to understand and translation or interpretive assistance can be provided for participants with limited English proficiency.

Once you have been provided with all the information you need, you can sign the informed consent document if you are still happy to participate in the research. But even once you have signed, you are free to withdraw at any time because the informed consent document is not a contract.

Other Things To Consider Before You Sign: Being On A Placebo

Comparative trials either compare an active treatment or procedure with another active treatment or procedure, or they compare an active treatment to a placebo (an inactive treatment that resembles the intervention).

This means that if you are in a comparative trial with a placebo control, there is a 50:50 chance that you will get the placebo. While placebo studies tend not to be used if they would put the participant at risk, placebo studies remain the fastest and most reliable way to demonstrate a new product's effectiveness. If you are assigned the placebo, you are not being exposed to the active intervention and its benefits. On the flip side, you are not being exposed to any harms either. Interestingly enough, many people assigned to a placebo in a double-blind trial still report some benefits and side effects (this is known as the "placebo-effect").

Other Things To Consider: Time Involved and Reimbursement

Some trials may require you to remain in a medical care facility for the duration of the trial, while others may not be so disruptive to your everyday life.

Make sure you understand how much you will be reimbursed for your time or what charges you may incur - some studies may require you to pay for any tests or the investigational drug and there may be extra travel or childcare costs that you will need to consider. It is important to know what your health insurance is likely to cover and who your health insurance company can call if they have any questions.

Without volunteers, clinical research would cease to exist. Although there are some risks with taking part in a clinical trial, there can be many benefits particularly if you have a particular medical condition and you have run out of effective treatment options. Weigh up the pros and cons and decide for yourself if it is worthwhile for you to participate in the study. Who knows, you might become part of history!

Finished: Ask The Expert: How Do Clinical Studies Work?

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Sources

  • Step 3. Clinical research. U.S. Food and Drug Administration. May, 2017. https://www.fda.gov/forpatients/approvals/drugs/ucm405622.htm#The_Investigational_New_Drug_Process
  • The Basics. NIH: Clinical Research Trials and You. National Institutes of Health. US Deaprtment of Health and Human Services. https://www.nih.gov/health-information/nih-clinical-research-trials-you/basics
  • What types of trials are there? Accord Clinical Research. https://www.accordclinical.com/clinical-study/types-of-clinical-trials/
  • Thadhani R. Formal trials versus observational studies. In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry Disease: Perspectives from 5 Years of FOS. Oxford: Oxford PharmaGenesis; 2006. Chapter 14. Available from: https://www.ncbi.nlm.nih.gov/books/NBK11597/
  • Literature Reviews: Types of Clinical Study Designs. Georgia State University Library. http://research.library.gsu.edu/c.php?g=115595&p=755213
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