Clinical Trials

Foundations for the Strongest Studies

By Jerrilyn Cambron
[Somatic Research]

Clinical trials are a type of experimental research. They may also be described as randomized clinical trials or randomized controlled trials (RCTs), controlled clinical trials, and randomized controlled clinical trials.
Whatever name you give them, clinical trials are considered the most meaningful type of study because the investigators have so much control over what happens to the subjects. In other study designs, the subjects make the final decision as to what exposures or treatments they receive. In clinical trials, however, the subjects agree to being placed in a group and to follow the instructions of the researcher.
Control Over Treatment and Subjects
Clinical trials are designed with strict protocols in place. Researchers use specific recruitment processes in order to enroll a specific type of subject. For example, some studies have open recruitment in which researchers will recruit from the general public through newspaper and radio advertisements. Other researchers will recruit through local physicians’ offices, particularly ones that specialize in the condition being studied.
Once subjects are recruited, they go through a baseline examination to determine if they are eligible for the study. Predesigned inclusion and exclusion criteria are assessed by the clinician. These criteria help narrow the type of subject in the study. For example, perhaps a study will focus only on subjects whose low-back pain is chronic rather than acute. Or perhaps one of the criteria would be that people cannot have other comorbidities because the other conditions might affect the way the subject responds to the treatment.
The measures that will be used to determine the outcomes are set prior to the start of the study as well. Researchers tend toward using outcome measures that have already gone through testing to determine validity and reliability, so they are truly measuring what they think they are measuring, and doing it with accuracy. For example, the Visual Analog Scale (VAS) is known as a valid and reliable outcome measure and has been used by many researchers and clinicians. New measures can be developed, but if they are not tested prior to utilization, they might give spurious outcomes and affect the results. It is important that quality outcome measures are used. 
In clinical trials, treatment protocols are frequently developed as well. Protocols for a clinical trial on the benefits of massage might include the type of massage, the body areas treated, the duration of each session, the number of sessions, and the take-home instructions. There is usually quite a bit of rigor when it comes to treatment protocols and these sometimes take the longest to develop.
Aside from the strong dependence on structure within the clinical trial, the other main factor in this study design is randomization—making sure that subjects are assigned to their treatment group randomly, or “by chance.” Most researchers use a random number generator, in the form of a computer program or written table, to assign the treatment groups. Some still use the old-fashioned method of rolling dice, where even numbers mean one treatment group and odd numbers mean the other treatment group. The method of randomization doesn’t much matter, as long as the treatment assignment of each patient occurs by chance, meaning neither the subject nor the clinician has any control over which group is assigned.
The main benefit of randomization is that the groups become inherently even in terms of demographics and clinical characteristics. We expect that with random assignment, we would have an even number of males and females in each group, the average age would be approximately the same, and the clinical conditions would be similar between the groups. This is similar to flipping a coin. If flipped enough times, we will get approximately the same number of heads as we do tails.
Without randomization, subjects would choose their own group. This may lead to significant differences between the groups. For example, if a clinical trial was designed to compare a massage treatment with surgery, subjects with more severe pain might be more likely to choose surgery and subjects with less severe pain might be more likely to choose massage. However, in research, we would like to know if massage benefits people with all levels of pain, just as we would like to know if surgery benefits all people, too. We would want to have a balance of people with mild, moderate, and severe pain in both groups, and randomization helps make this happen.
Another benefit of randomization is that it decreases expectation bias. When people get to choose which treatment they will receive, they typically pick the one from which they expect the best results. This affects the study outcomes because if the subject expects to get better, they are more likely to report that they did get better. However, with randomization, subjects are much less likely to have expectations, hopefully leading to more accurate results. 
Placebo Group
Clinical trials are the only study design that can have a placebo group. A placebo (or sham) is like a sugar pill. It is a treatment provided to a subject in which no benefits are expected by the clinician. There are many ethical issues surrounding placebos. For example, is it ethical to pretend that a subject will benefit from something the researchers know to be fake? Is it ethical to withhold treatment from subjects in order to provide them with a placebo? Finally, is it ethical not to tell the subjects during the informed consent process that they might get a placebo, or should they be told up front so they can truly make an informed decision as to whether they want to participate in the study?
Placebo treatments began in pharmaceutical studies as a way to determine if subjects were getting better just because they were being cared for, or if the actual treatment was helping. There is an effect, called the placebo effect, in which the subject improves even though no actual treatment was rendered. In these cases, we do not know why the subject improved. It may be natural history, meaning they would have improved on their own anyway. However, many people think that the subjects get better because they believe they will get better, or because they feel cared for by health professionals. It is an interesting phenomenon that should not be dismissed. If a subject being treated with a placebo improves, was the placebo really a placebo, or was it a different form of treatment that we don’t fully understand or know how to measure?
Another important topic with placebo treatment is that in some studies the subjects find it easy to determine if they are in the placebo group or not. This is a problem because it will affect the overall results. If a person believes he is in the placebo group, he will not score as well on the outcome measures because he does not think he should be doing better. Vice versa, if the subjects in the active treatment group know they are getting the active treatment, they will be more likely to show an improvement on the outcome measures because they think they should be doing better. All studies that include a placebo group should ask their subjects which group they think they are in, so the amount of potential bias can be determined.
In some studies, a placebo treatment is not possible. For example, if we were going to do a study comparing massage with a placebo, what would our placebo look like? Would the therapist touch the subject at all? Would the therapist do massage but not on the areas that need treatment? A placebo for massage does not make sense; therefore, placebo is not usually utilized in massage clinical trials.
Double Blinding
The final major factor found in clinical trials is double blinding. This means that neither the subject nor the clinician who provides the treatment or measures the outcomes knows which treatment the subject received.
A positive aspect of double blinding is that if the clinician doesn’t know the subject’s group assignment, he or she will not be biased when measuring the outcomes. All clinicians come with inherent bias, meaning they believe one group will outperform the other. This bias can lead to subconscious decisions when measuring outcomes. However, double blinding can remove those biases because the clinician does not know to which group each subject belongs.
It is rare to have double blinding in massage clinical trials because both the subjects and the clinician are aware of the type of treatment being rendered. But these types of trials frequently have single blinding by including a research clinician who does not know the treatment allocation and who takes all measurements. This person does not know which group the patients are in, and measures all subjects in the same manner.
Downside to Clinical Trials
While all of this consistency and rigor allows researchers the ability to describe outcomes based on a specific treatment for a specific condition in a specific population, the results generated from clinical trials are not necessarily true to life. Most clinicians would not treat every patient the same, using the same treatment protocols over the same amount of time. But researchers need to start somewhere and will typically continue doing research with modified populations and treatments to determine what treatment is beneficial for what type of condition.
How Does This Affect You?
The bottom line is clinical trials are considered the strongest study design because of their rigor. They can include structured treatments and outcome measures, randomization to treatment groups, placebo control groups, and double blinding. All of this structure helps the reader better understand the specifics of what treatment led to what outcome, but they can also be seen as being too far from real clinical practice.
What does this mean to you? First, when you are searching in PubMed for articles, try to find clinical trials. They carry the most weight in terms of evidence, and they are considered the most important when discussing them with other health-care professionals. Second, when reading research articles, pay attention to the way the study was designed. Was there randomization, blinding, or a placebo group?
All research is important to the growth of the literature. However, clinical trials carry the most weight.

Jerrilyn Cambron, DC, PhD, MPH, LMT, is an educator at the National University of Health Sciences and president-elect of the Massage Therapy Foundation. Contact her at

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