Randomized Controlled Clinical Intervention Study (RCT)
A Randomized Controlled Clinical Intervention Study (RCT) is a controlled clinical intervention study (of a experimental medical intervention) that is a randomized controlled experiment where intervention subjects are randomly assigned to clinical therapy groups.
- AKA: Randomized CT.
- Context:
- It can (typically) be associated with a RCT Protocol Document, that specifies Clinical Research Endpoint.
- It can (typically) be composed of Randomized Clinical Trial Subtasks.
- It can range from being a Placebo-Controlled Randomized Clinical Trial to being an Active-Controlled Randomized Clinical Trial.
- It can range from being a Proposed RCT, to being an Active RCT, to being a Concluded RCT (such as a positive RCT).
- It can range from being a Centralized Randomized Clinical Trial/Centralized RCT to being a Decentralized Randomized Clinical Trial/Decentralized RCT.
- It can range from being a Prevention RCT to being a Screening RCT to being a Treatment RCTs.
- It can range from being a Pragmatic RCT to being an Explanatory RCT.
- It can range from being a Drug RCT, to being a Medical Device RCT, to being a Clinical Procedure RCT.
- It can range from being a Confirmatory Clinical Trial to being an Exploratory Clinical Trial.
- It can range from being an Superiority Clinical Trial, to being a Equivalence Clinical Trial, to being a Inferiority Clinical Trial, to being a Noninferiority Clinical Trial.
- It can range from being a Phase-II Clinical Trial to being a Phase-III Clinical Trial.
- It can range from being a Static Clinical Trial to being an Adaptive Clinical Trial.
- It can be managed by a Clinical Trial Management System.
- It can be monitored by a Clinical Trial Monitoring System.
- It can be designed by a Clinical Trial Design System.
- It can assign patients/clinical trial participants using a Clinical Trial Participant Allocation System.
- …
- Example(s):
- a Randomized Placebo-Controlled Clinical Trial,
- a Randomized Comparative-Effectiveness Clinical Trial,
- a Multi-Arm Randomized (MAR) Clinical Trial,
- one listed in ClinicalTrials.gov [1].
- a Pfizer-led Ramipril for the Treatment of COVID-19 / NCT04366050 [2]
- a NCT01720524: Sildenafil as Treatment for Newborn Pulmonary Hypertension.
- a Disease Prevention Clinical Trial, such as a Vaccination Trial, such as a Covid-19 Vaccine Clinical Trial.
- a Medical Treatment Clinical Trail, such as a Antiviral Trial, such as a Covid-19 Antiviral Clinical Trial.
- a Quality of Life Clinical Trial, such as an Oncology Clinical Trial.
- a Health Screening Clinical Trial,
- a Medical Diagnostic Clinical Trial,
- a Genetic Disorder Clinical Trial,
- an Epidemiological Clinical Trial,
- a Compassionate Use Clinical Trail.
- an RCT with Two Treatment Groups.
- a Systolic Blood Pressure Intervention Trial (SPRINT).
- …
- Counter-Example(s):
- an Uncontrolled Randomized Clinical Trial.
- a Uncontrolled Nonrandomized Clinical Study, such as: a Phase-0 Clinical Trial, a Phase-I Clinical Trial, a Phase-IV Clinical Trial.
- a Randomized Controlled Animal Study.
- an Observational Clinical Study.
- a Non-Randomized Clinical Trial, such as a Nonrandomized Trial with Historical Controls.
- a Pilot Clinical Study (a pilot study).
- a Before-After Clinical Research Study, when subjects are compared to themselves but not randomized.
- See: Subject-level Randomized Experiment, Control Group, Treatment Group, Clinical Study Phase, Clinical Study Design, Placebo Effect, Nocebo Effect, ClinicalTrials.gov, AIDS Clinical Trials Group, Contract Research Organization.
References
2021a
- (Wikipedia, 2021) ⇒ https://en.wikipedia.org/wiki/Clinical_trial Retrieved:2021-11-13.
- Clinical trials are experiments or observations done in clinical research. Such prospective biomedical or behavioral research studies on human participants are designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary in size and cost, and they can involve a single research center or multiple centers, in one country or in multiple countries. Clinical study design aims to ensure the scientific validity and reproducibility of the results. Costs for clinical trials can range into the billions of dollars per approved drug. The sponsor may be a governmental organization or a pharmaceutical, biotechnology or medical device company. Certain functions necessary to the trial, such as monitoring and lab work, may be managed by an outsourced partner, such as a contract research organization or a central laboratory. Only 10 percent of all drugs started in human clinical trials become approved drugs.
2021c
- (Wikipedia, 2021) ⇒ https://en.wikipedia.org/wiki/Clinical_trial#Types Retrieved:2021-12-28.
- Clinical trials are classified by the research objective created by the investigators.
- In an observational study, the investigators observe the subjects and measure their outcomes. The researchers do not actively manage the study.
- In an interventional study, the investigators give the research subjects an experimental drug, surgical procedure, use of a medical device, diagnostic or other intervention to compare the treated subjects with those receiving no treatment or the standard treatment. Then the researchers assess how the subjects' health changes.
- Trials are classified by their purpose. After approval for human research is granted to the trial sponsor, the U.S. Food and Drug Administration (FDA) organizes and monitors the results of trials according to type:
- Prevention'' trials look for ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include drugs, vitamins or other micronutrients, vaccines, or lifestyle changes.
- Screening trials test for ways to identify certain diseases or health conditions.
- Diagnostic trials are conducted to find better tests or procedures for diagnosing a particular disease or condition.
- Treatment trials test experimental drugs, new combinations of drugs, or new approaches to surgery or radiation therapy.
- Quality of life trials (supportive care trials) evaluate how to improve comfort and quality of care for people with a chronic illness.
- Genetic trials are conducted to assess the prediction accuracy of genetic disorders making a person more or less likely to develop a disease.
- Epidemiological trials have the goal of identifying the general causes, patterns or control of diseases in large numbers of people.
- Compassionate use trials or expanded access trials provide partially tested, unapproved therapeutics to a small number of patients who have no other realistic options. Usually, this involves a disease for which no effective therapy has been approved, or a patient who has already failed all standard treatments and whose health is too compromised to qualify for participation in randomized clinical trials. Usually, case-by-case approval must be granted by both the FDA and the pharmaceutical company for such exceptions. * Fixed trials consider existing data only during the trial's design, do not modify the trial after it begins, and do not assess the results until the study is completed. * Adaptive clinical trials use existing data to design the trial, and then use interim results to modify the trial as it proceeds. Modifications include dosage, sample size, drug undergoing trial, patient selection criteria and "cocktail" mix. Adaptive trials often employ a Bayesian experimental design to assess the trial's progress. In some cases, trials have become an ongoing process that regularly adds and drops therapies and patient groups as more information is gained. The aim is to more quickly identify drugs that have a therapeutic effect and to zero in on patient populations for whom the drug is appropriate.
- Clinical trials are conducted typically in four phases, with each phase using different numbers of subjects and having a different purpose to construct focus on identifying a specific effect.
- Clinical trials are classified by the research objective created by the investigators.
2021
- (Wikipedia, 2021) ⇒ https://en.wikipedia.org/wiki/Randomized_controlled_trial#Definition_and_examples Retrieved:2021-12-28.
- An RCT in clinical research typically compares a proposed new treatment against an existing standard of care; these are then termed the 'experimental' and 'control' treatments, respectively. When no such generally accepted treatment is available, a placebo may be used in the control group so that participants are blinded to their treatment allocations. This blinding principle is ideally also extended as much as possible to other parties including researchers, technicians, data analysts, and evaluators. Effective blinding experimentally isolates the physiological effects of treatments from various psychological sources of bias.
The randomness in the assignment of participants to treatments reduces selection bias and allocation bias, balancing both known and unknown prognostic factors, in the assignment of treatments. Blinding reduces other forms of experimenter and subject biases.
A well-blinded RCT is considered the gold standard for clinical trials. Blinded RCTs are commonly used to test the efficacy of medical interventions and may additionally provide information about adverse effects, such as drug reactions. A randomized controlled trial can provide compelling evidence that the study treatment causes an effect on human health.
The terms “RCT” and "randomized trial" are sometimes used synonymously, but the latter term omits mention of controls and can therefore describe studies that compare multiple treatment groups with each other in the absence of a control group. Similarly, the initialism is sometimes expanded as "randomized clinical trial" or "randomized comparative trial", leading to ambiguity in the scientific literature. Not all RCTs are randomized controlled trials (and some of them could never be, as in cases where controls would be impractical or unethical to use). The term randomized controlled clinical trial is an alternative term used in clinical research; however, RCTs are also employed in other research areas, including many of the social sciences.
- An RCT in clinical research typically compares a proposed new treatment against an existing standard of care; these are then termed the 'experimental' and 'control' treatments, respectively. When no such generally accepted treatment is available, a placebo may be used in the control group so that participants are blinded to their treatment allocations. This blinding principle is ideally also extended as much as possible to other parties including researchers, technicians, data analysts, and evaluators. Effective blinding experimentally isolates the physiological effects of treatments from various psychological sources of bias.
2018
- (Suvarnaamesh, 2018) ⇒ Viraj R. Suvarnaamesh. (2018). “Real World Evidence (RWE) - Are We (RWE) Ready?. ” Perspectives in Clinical Research, 9(2).
- QUOTE: ... What is real-world evidence? Obviously, evidence that is generated or exists in the real world. Why is it important? Typically, evidence generated within a randomized controlled clinical trial (RCT) is considered higher than that in the real world. Where hypotheses are generated double blinding and randomization (which ensures every patient has an equal chance of being allocated to treatment A or treatment B) are ways of ensuring that comparable cohorts are created, and bias is minimized to the extent possible. Naturally, a hypothesis can be tested within an RCT. However, there are limitations of an RCT. For example, in an RCT, there are inclusion and exclusion criteria. These eligibility criteria ensure that a homogeneous and representative sample is collected. However, in the real world, can any patient be excluded? Data from an RCT can only be extrapolated to the kind of patients who were eligible for the RCT. Hence, there are limitations of generalizability. Moreover, that is where real-world evidence comes in, to supplement data from RCTs, and hopefully bridge the gap between the controlled environment of an RCT and the harsh realities of the real world. (Nallamothu et al., 2008) ...
... In an ideal world, both the RCT and real-world evidence coexist and one can even do large simple studies, where the two elements are blended such that the results do mirror what happens in the real world. Such hybrid, efficacy-effectiveness studies can help in advancing a closer correlation to the real world within a clinical development program. However, real-world studies are fraught with their own limitations. Can one randomize in the real world? What about retrospective analyses of databases (electronic medical records) in the real world or comparative effectiveness research? They have their uses viz., in comparing the cost-effectiveness of two regimens in the real world, beyond the rigors of an RCT. ...
- QUOTE: ... What is real-world evidence? Obviously, evidence that is generated or exists in the real world. Why is it important? Typically, evidence generated within a randomized controlled clinical trial (RCT) is considered higher than that in the real world. Where hypotheses are generated double blinding and randomization (which ensures every patient has an equal chance of being allocated to treatment A or treatment B) are ways of ensuring that comparable cohorts are created, and bias is minimized to the extent possible. Naturally, a hypothesis can be tested within an RCT. However, there are limitations of an RCT. For example, in an RCT, there are inclusion and exclusion criteria. These eligibility criteria ensure that a homogeneous and representative sample is collected. However, in the real world, can any patient be excluded? Data from an RCT can only be extrapolated to the kind of patients who were eligible for the RCT. Hence, there are limitations of generalizability. Moreover, that is where real-world evidence comes in, to supplement data from RCTs, and hopefully bridge the gap between the controlled environment of an RCT and the harsh realities of the real world. (Nallamothu et al., 2008) ...
2008
- (Nallamothu et al., 2008) ⇒ Brahmajee K. Nallamothu, Rodney A. Hayward, and Eric R. Bates. (2008). “Beyond the Randomized Clinical Trial: The Role of Effectiveness Studies in Evaluating Cardiovascular Therapies.” Circulation 118, no. 12
- QUOTE: ... It would be desirable to rely solely on RCTs to guide clinical practice, but this is simply not feasible. At the root of the problem is the fact that RCTs are typically restricted to evaluating specific discrete interventions one at a time. This restriction limits their ability to (1) directly assess complex interactions within a study arm (ie, interactions between different blood pressure medicines used to obtain tight blood pressure control), (2) continuous relationships (such as what blood pressure or cholesterol levels are optimal), and (3) whether the benefits or harm of a treatment are drug-specific or mechanistic. As a result, traditional RCTs focus more on evaluating the efficacy of simple therapies like drugs and less on the delivery of care. ...
... Furthermore, even within these highly selected patients there can be heterogeneity in the extent of benefit found with a therapy. For example, scenarios may exist where an average treatment effect favors a therapy because of its benefit to a few high-risk patients, although most individuals in the study gain little from it. ...
... Finally, RCTs often require enormous resource investments and may be inherently limited in their ability to investigate certain issues for logistical or ethical reasons. The recently completed Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, which compared optimal medical therapy with and without percutaneous coronary intervention (PCI) in 2287 patients,4 resulted in nearly $60 million in total costs shared by both public and private sponsors (personal communication, William E. Boden, MD, 2008). ...
- QUOTE: ... It would be desirable to rely solely on RCTs to guide clinical practice, but this is simply not feasible. At the root of the problem is the fact that RCTs are typically restricted to evaluating specific discrete interventions one at a time. This restriction limits their ability to (1) directly assess complex interactions within a study arm (ie, interactions between different blood pressure medicines used to obtain tight blood pressure control), (2) continuous relationships (such as what blood pressure or cholesterol levels are optimal), and (3) whether the benefits or harm of a treatment are drug-specific or mechanistic. As a result, traditional RCTs focus more on evaluating the efficacy of simple therapies like drugs and less on the delivery of care. ...