Why is equipoise important in clinical trials

More recently, however, most RCTs have migrated toward directional hypotheses, intended to demonstrate the effectiveness of one intervention over another. One of the reasons for this change is publication bias, which is the tendency for journals to accept papers for publication based on the direction or strength of the study findings; studies have a higher likelihood of being published if they show a significant difference between groups.

This number depends largely on the estimated effect size. Despite, and perhaps, due to the challenges of meeting statistical significance with a directional hypothesis, the risks associated with experimenter and patient biases are compelling.

Within manual therapy, two types of interventions are generally compared. The first involves selected techniques such as manipulation, mobilization, selected neurodynamics, or any procedure that is specific to a particular manual therapy philosophy paired against one another, while the second involves comparison of particular systems such as McKenzie versus orthopaedic manipulative therapy.

This effect may be observed when the control treatment does not reflect an intervention in a way that it is typically used in clinical practice e. Nearly all manual therapy interventions, with the possible exception of thrust manipulation, have been used both as treatments and sham interventions.

An intervention that — through intention or training — would have a meaningful effect when applied by one clinician may be no more than a sham control when applied by another. There are a number of means for correcting for this potentially problematic element. A method called an expertise-based RCT 25 involves randomizing patients to practitioners who specialize in the dedicated intervention within a trial. For example, for a trial comparing manipulation versus soft tissue mobilization, four clinicians who specialize in manipulation of the cervical spine could serve as research participants as could four clinicians who specialize in soft tissue mobilization.

Each patient enrolled in the study could be randomized to a specific clinician, versus randomization to a particular treatment. Ideally, this would involve practitioners of similar levels of training, and include multiple therapists in each group. This would increase the likelihood that the variable examined is the technique or method, rather than the skill of a particular clinician. A similar method to expertise-based RCTs is an equipoise-stratified design. This design 26 involves full pre-randomization recognition of clinician biases toward a specific intervention and balancing of these biases during the study groupings through matching.

Equipoise-stratified designs are more appropriate for models, which involve numerous interventions or interventions that are multimodal. This also results in questionable randomization, which among other concerns will eliminate the ability to assess treatment modifiers. Additionally, this design introduces another variable, as the ability of the clinician to choose the correct treatment is confounded with the effect of the treatment.

Consequently the trials would need to involve a large number of subjects for the process to work. Clinician blinding is an important step in maintaining equipoise and should be a goal of clinical trials, yet achieving this goal is so difficult in manual therapy studies that some reviewers have excluded it as a factor in quality assessment. A systematic review by Kent et al. Clinicians trained in Mechanical Diagnosis and Therapy may interact differently with patients who received treatment matched to their classification versus movement in the opposite direction, which they expect will increase symptoms.

Long et al. This study shows the challenges to maintaining equipoise, as patients may not agree to the intended research design. Because of the intimate nature of manual therapy interventions, personal and clinical equipoise are two ingredients necessary for a truly unbiased manual therapy-based RCT. Further work is needed to define the full extent to which a lack of personal and clinical equipoise influences the findings of a manual therapy-based randomized clinical trial.

This will require careful evaluation of the presence of clinical and personal equipoise prior to the implementation of the study. Until clinical equipoise is clearly accounted for, studies at risk for violating equipoise should be interpreted with caution.

National Center for Biotechnology Information , U. J Man Manip Ther. Chad Cook 1 and Charles Sheets 2. Author information Copyright and License information Disclaimer. Email: ude. What should prospective patients or currently enrolled patients be told? But according to Freedman, research ethicists from the s and s clearly thought that this kind of information not only could have relevance for the conduct of trials but could theoretically jeopardize the entire research enterprise.

Freedman mentioned some solutions that ethicists had previously proposed to deal with this thorny problem. One of them is actually already part of clinical trial methodology: the blinding of the investigators. In the course of a trial, accrued outcomes are not analyzed by the physicians involved in the care of patients but by an independent data monitoring committee. That way, the clinicians are kept from being biased by the data as it accumulates.

But Freedman rightly pointed out that, from an ethical standpoint, blinding clinicians is like sticking their heads in the sand:. If interim results would disturb equipoise, the investigators are obliged to gather and use that information. Clearly, equipoise highlights the tension between the therapeutic aims of medicine and the scientific aims of research.

Other proposals have been suggested. Trial subjects, therefore, should not necessarily expect to get the best care possible. A third one—at the opposite end of the autonomy spectrum—was to simply conscript patients into participating in clinical trials. Ethics be damned! Not only are benefits tallied, but various side-effects as well. In such a situation, theoretical equipoise is impossible to maintain or even hold to begin with. Clearly, clinical equipoise as stipulated by Freedman is much less liable to be disturbed than the original concept.

So long as there is disagreement among a sufficiently large number of colleagues or clinicians, equipoise can be said to exist, and a clinical trial can be justified on ethical grounds:. At the same time, it would be emphasized that this preference is not shared by others. Medicine is a collegial enterprise. Rare is the physician who holds opinions in isolation, without the influence or agreement of others.

In my debate with Dr. Cifu I remarked that if the community of intensivists remains divided on the question of the benefit of early versus delayed intubation for severe COVID, then they may agree to conduct a clinical trial and would be justified in doing so.

The EBM takeover of medicine has changed the concept of equipoise in the opposite way to that which Freedman feared. After all, it is the central dogma of EBM that there is no firm knowledge about a treatment unless the evidence comes from a well-conducted, randomized, blinded clinical trial. If there is no randomized controlled trial, there is no substantive knowledge.

As long as EBM reigns, the demand for equipoise is self-fulfilling. But pandemics are not friendly to equipoise. Here, Yeh and colleagues stress the valid point that a pandemic is precisely not a time to send caution to the wind. Traditional pathways for evaluating new treatments through randomized trials hinge on establishing and maintaining equipoise at a broad public health level, but also at the bedside where wrenching decisions are made in real-time. Your contribution can help future generations lead healthier, potentially disease-free lives.

When you choose to participate in a clinical trial at Stamford Health, you become a partner in scientific discovery! We have many clinical trials that allow virtual visits that utilize digital health technologies so that you can participate from the convenience of the home rather than traveling to Stamford Health.

Each year, the Office of Research conducts between 80 and 90 clinical trials in several therapeutic areas such as: cardiology , electrophysiology , emergency medicine , endocrinology , gastroenterology , hematology , infectious disease , internal medicine, interventional cardiology , nephrology , oncology , pain management , and pulmonology.

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