What are Clinical Trials?

In this Article (Index)

• Scientific Method
• Observational Studies
• Clinical Trials
• Randomized trials
• Control Group
• Placebo
• Blind trials
• Placebo Effect

Scientific Method

Medical science is also based on the scientific method, a way of acquiring knowledge that has developed over the past four hundred years.

Its goal is to establish facts through a rigorous and objective process that can be summarized as follows:

1. Make an observation
2. Formulate a hypothesis to explain what has bee observed
3. Carry out an experiment to test the hypothesis
4. Analyze the outcome and validate the hypothesis or start over again

Clinical research is focused on studying human beings themselves to imporve the wellbeing of humanity, it often involves ethical issues and carefully planned trials and experiments to validate hypothesis.

It involves different types of "experiments", from clinical judgement, case reports, and observational studies to clinical trials, all of them involving human beings. We will describe each of them in the following sections.

Observational Studies

In an observational study, a group of people living their lives normally, in their regular settings are monitored on a regular basis by researchers. They don't test medical devices or drugs, they observe a people and record information about them and measure data, but there is no attempt to modify the outcome. These studies may help identify fields to be studied in detailed clinical trials (1).

Observational studies merely observe a situation and report it. There are different types of observational studies.

Types of Observational Studies

Case reports and case series

A case report is an atypical case that appears in clinical practice, something unusual, out of the norm. This unique case is described as a case report and presented tho the medical community.

Case series is when a group of patients present the same unusual condition, each of them a case report, indicating that there may be some new medical condition that should be explored.

Ecologic study

It is a study that describes some features in a population group. For instance measuring the incidence of a type of cancer and the intake of fat per capita. This could show there is a positive link (correlation) between a high dietary fat intake and an increase in that type of cancer. Another example could study if hospital admissions for lung-related ailments in a given city increase on days when air pollution levels are higher. But that is all it can do, find a correlation.

Case-control study

These studies compare two groups one of them (cases) could be subjects with a disease or condition, the other subects don't have the disease (controls).
The researcher then looks at all the historical factors reported by the subjects trying to find out if some kind of exposure is more common among cases than in controls. If it it is, the study may conclude that the exposure is linked to the condition being studied. It may be biased by the selective recall of the subjects if it is based on lifestyle reporting.

An example is the link between HIV and Kaposi's sarcoma, a rare type of cancer. Comparing a control group without the cancer and a group with the cancer the researcher would notice that those with Kaposi's sarcoma are more likely to have HIV and then conclude that HIV is a risk factor for developing that illness.

Cohort study

These studies compare two groups just like Case-control studies, but cohort studies are more expensive and time-consuming. There are two types of cohort studies:

• Prospective cohort studies where it follows studies over a period of time (often years) from the first exposure till the outcome. This is cosly and takes time. Example: female nurses who smoke and those who don't and follow them over the years to study the prevalence of lung cancer.
• Retrospective cohort studies where a certain population (cohort) with and without the exposure to a certain condition (smoking) is assessed on the outcome (developing lung cancer) based on past records.

Examples of observational studies:

• Does a vegetarian diet improve health?
• Does walking improve health?
• Fat consumption and heart health
• Cancer prevalence and exposure to certain chemicals

The participants enroll and provide regular data through questionnaires, reporting eating habits, lifestyle information, weight, blood pressure, etc.

Clinical Trials

Also called therapeutic trials, it compares two or more groups of subjects with a condition or disease that are placed in different groups that receive different treatments. And the outcome is recorded.

One of the first studies of this type was conducted by James Lind in 1747 on a group of sailors to study the impact of diet on scurvy. They were divided into six different groups, each one eating the same food but adding a different supplement to it. The group receiving 2 oranges and one lemon showed the best outcome compared to the others (who received, cider, vinegar, barley water, etc.) This proved a casual relationship between a successful treatment for scurvy and citrics.

They are used to validate if a surgical or medical therapy, a drug, diet, medical device is safe and effective in treating a condition. It also answers questions like: Is it better than an existing therapy? Is it less harmful? Does it improve life quality? Does it diagnose a disease earlier, before symptoms appear?

There are different types of trials, as the idea is to provide unbiased and objective data.

Randomized trials

As its name indicates, people taking part in a study are assigned into one of the subject groups at random. A process known as "randomization". This is done using a computer program to ensure it is unbiased and really random.

It avoids the unconscious bias by which a doctor may place patients who are more ill than others in one of the groups, causing it to respond badly to the treatment and appear as ineffective, but actually the poor outcome is due to its subjects being in worse conditions than those of the other groups.

Randomization ensures that if there are differences in the outcomes of different groups it is caused by the treatment and not by differences in the participants (2).

Control Group

This is the group that receives the standard treatment, just as they would if they were not part of the trial.

Placebo

It is possible that there is no standard treatment for those in the control group or that they have already had all the currently available treatments. In this case they will be assigned a "dummy" treatment or placebo

Placebos look, feel, taste and smell exactly like the genuine treatment. They make take the form of pills, injections, or drinks. The idea behind a placebo is that a real treatment should be more effective than a dummy drug (saline solution, starch).

For ethical reasons, researchers only use a placebo if no standard treatment is available. It wouldn't be acceptable to give a placebo to patients who really need treatment for their condition.

Blind trials

To add even more certainty and eliminate bias, blind trials are employed, the idea is that the participants and or the researchers don't know who is receiving the standard treatment or placebo and who is receiving the alternate ones under trial.

• Blind trial. Single blind trials are those where the subjects or patients don't know what treatment they are getting. Their medicines look identical so they can't say what they are having.
• Double blind trial. Neither the patients or the researchers know who is getting what. Each patient is given a code number and randomly assigned to a group. The treatment is sent to the doctor to administer it to the patients with their code number printed on it; it could be placebo, standard treatment or the new one. The doctor does not know what he is giving the patient, who does not know in which group he or she is.
  At the end of the trial they learn which group they were in. In an emergency the researcher could learn (via code number) which group the patient is in and check if it wasn't caused by the trial.

Placebo Effect

The placebo effect is an intriguing phenomenon by which the dummy treatment or placebo causes an improvement in the patient's conditions.

Due to the inert nature of the sham medicine in the placebo, this improvement can only be caused by the patient's positive perception about the treatment and its expected outcome.

The brain somehow works together with the body reducing the perception of pain, making the subject feel better, improving moods, and self awareness. Somehow the brain is telling the body to get better.

Placebo effects also appear with the regular treatments, the baseline one that is used normally and is being compared to the novel therapy.

As can be expected, improved conditions due to a placebo effect influence the outcome of clinical trials.

The placebo effect doesn't cure the disease it only makes the subject feel better.