A randomized controlled trial (or randomized control trial;RCT) is a type of scientific (often medical) experiment that aims to reduce certain sources of bias when testing the effectiveness of new treatments; this is accomplished by randomly allocating subjects to two or more groups, treating them differently, and then comparing them with respect to a measured response. One group—the experimental group—has the intervention being assessed, while the other—usually called the control group—has an alternative condition, such as a placebo or no intervention. The groups are followed under conditions of the trial design to see how effective the experimental intervention was. Treatment efficacy is assessed in comparison to the control. There may be more than one treatment group or more than one control group.
Random assignment or random placement is an experimental technique for assigning human participants or animal subjects to different groups in an experiment using randomization, such as by a chance procedure or a random number generator. This ensures that each participant or subject has an equal chance of being placed in any group. Random assignment of participants helps to ensure that any differences between and within the groups are not systematic at the outset of the experiment. Thus, any differences between groups recorded at the end of the experiment can be more confidently attributed to the experimental procedures or treatment.
A placebo is an inert substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets, inert injections, sham surgery, and other procedures.
The trial may be blinded, in which information which may influence the participants is withheld until after the experiment is complete. A blind can be imposed on any participant of an experiment, including subjects, researchers, technicians, data analysts, and evaluators. Good blinding may reduce or eliminate some sources of experimental bias.
In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from the placebo effect, the observer effect, confirmation bias, and other sources. A blind can be imposed on any participant of an experiment, including subjects, researchers, technicians, data analysts, and evaluators. In some cases, while blinding would be useful, it is impossible or unethical. For example, it is not possible to blind a patient to their treatment in a physical therapy intervention. A good clinical protocol ensures that blinding is as effective as possible within ethical and practical constrains.
Bias is disproportionate weight in favor of or against an idea or thing, usually in a way that is closed-minded, prejudicial, or unfair. Biases can be innate or learned. People may develop biases for or against an individual, a group, or a belief. In science and engineering, a bias is a systematic error. Statistical bias results from an unfair sampling of a population, or from an estimation process that does not give accurate results on average.
The randomness in the assignment of subjects to groups 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.
Selection bias is the bias introduced by the selection of individuals, groups or data for analysis in such a way that proper randomization is not achieved, thereby ensuring that the sample obtained is not representative of the population intended to be analyzed. It is sometimes referred to as the selection effect. The phrase "selection bias" most often refers to the distortion of a statistical analysis, resulting from the method of collecting samples. If the selection bias is not taken into account, then some conclusions of the study may be false.
The observer-expectancy effect is a form of reactivity in which a researcher's cognitive bias causes them to subconsciously influence the participants of an experiment. Confirmation bias can lead to the experimenter interpreting results incorrectly because of the tendency to look for information that conforms to their hypothesis, and overlook information that argues against it. It is a significant threat to a study's internal validity, and is therefore typically controlled using a double-blind experimental design.
A well-blinded RCT is often 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.
In medicine and statistics, a gold standard test is usually the diagnostic test or benchmark that is the best available under reasonable conditions. Other times, a gold standard is the most accurate test possible without restrictions.
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 and known interventions that warrant further study and comparison. Clinical trials generate data on 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 that the therapy is 'safe' or effective, only that the trial may be conducted.
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 randomized clinical trials are randomized controlled trials (and some of them could never be, as in cases where controls would be impractical or unethical to institute). 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.
Scientific literature comprises scholarly publications that report original empirical and theoretical work in the natural and social sciences, and within an academic field, often abbreviated as the literature. Academic publishing is the process of contributing the results of one's research into the literature, which often requires a peer-review process. Original scientific research published for the first time in scientific journals is called the primary literature. Patents and technical reports, for minor research results and engineering and design work, can also be considered primary literature. Secondary sources include review articles and books. Tertiary sources might include encyclopedias and similar works intended for broad public consumption.
Clinical research is a branch of healthcare science that determines the safety and effectiveness (efficacy) of medications, devices, diagnostic products and treatment regimens intended for human use. These may be used for prevention, treatment, diagnosis or for relieving symptoms of a disease. Clinical research is different from clinical practice. In clinical practice established treatments are used, while in clinical research evidence is collected to establish a treatment.
The first reported clinical trial was conducted by James Lind in 1747 to identify treatment for scurvy.Randomized experiments appeared in psychology, where they were introduced by Charles Sanders Peirce and Joseph Jastrow in the 1880s, and in education. Later, in the early 20th century, randomized experiments appeared in agriculture, due to Jerzy Neyman and Ronald A. Fisher. Fisher's experimental research and his writings popularized randomized experiments.
James Lind was a Scottish doctor. He was a pioneer of naval hygiene in the Royal Navy. By conducting one of the first ever clinical trials, he developed the theory that citrus fruits cured scurvy. He argued for the health benefits of better ventilation aboard naval ships, the improved cleanliness of sailors' bodies, clothing and bedding, and below-deck fumigation with sulphur and arsenic. He also proposed that fresh water could be obtained by distilling sea water. His work advanced the practice of preventive medicine and improved nutrition.
Scurvy is a disease resulting from a lack of vitamin C. Early symptoms of deficiency include weakness, feeling tired, and sore arms and legs. Without treatment, decreased red blood cells, gum disease, changes to hair, and bleeding from the skin may occur. As scurvy worsens there can be poor wound healing, personality changes, and finally death from infection or bleeding.
In science, randomized experiments are the experiments that allow the greatest reliability and validity of statistical estimates of treatment effects. Randomization-based inference is especially important in experimental design and in survey sampling.
The first published RCT in medicine appeared in the 1948 paper entitled "Streptomycin treatment of pulmonary tuberculosis", which described a Medical Research Council investigation.One of the authors of that paper was Austin Bradford Hill, who is credited as having conceived the modern RCT.
By the late 20th century, RCTs were recognized as the standard method for "rational therapeutics" in medicine.As of 2004, more than 150,000 RCTs were in the Cochrane Library. To improve the reporting of RCTs in the medical literature, an international group of scientists and editors published Consolidated Standards of Reporting Trials (CONSORT) Statements in 1996, 2001 and 2010, and these have become widely accepted. Randomization is the process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce the bias.
Although the principle of clinical equipoise ("genuine uncertainty within the expert medical community... about the preferred treatment") common to clinical trialshas been applied to RCTs, the ethics of RCTs have special considerations. For one, it has been argued that equipoise itself is insufficient to justify RCTs. For another, "collective equipoise" can conflict with a lack of personal equipoise (e.g., a personal belief that an intervention is effective). Finally, Zelen's design, which has been used for some RCTs, randomizes subjects before they provide informed consent, which may be ethical for RCTs of screening and selected therapies, but is likely unethical "for most therapeutic trials."
Although subjects almost always provide informed consent for their participation in an RCT, studies since 1982 have documented that RCT subjects may believe that they are certain to receive treatment that is best for them personally; that is, they do not understand the difference between research and treatment.Further research is necessary to determine the prevalence of and ways to address this "therapeutic misconception".
The RCT method variations may also create cultural effects that have not been well understood.For example, patients with terminal illness may join trials in the hope of being cured, even when treatments are unlikely to be successful.
In 2004, the International Committee of Medical Journal Editors (ICMJE) announced that all trials starting enrolment after July 1, 2005 must be registered prior to consideration for publication in one of the 12 member journals of the committee.However, trial registration may still occur late or not at all. Medical journals have been slow in adapting policies requiring mandatory clinical trial registration as a prerequisite for publication.
One way to classify RCTs is by study design. From most to least common in the healthcare literature, the major categories of RCT study designs are:
An analysis of the 616 RCTs indexed in PubMed during December 2006 found that 78% were parallel-group trials, 16% were crossover, 2% were split-body, 2% were cluster, and 2% were factorial.
RCTs can be classified as "explanatory" or "pragmatic."Explanatory RCTs test efficacy in a research setting with highly selected participants and under highly controlled conditions. In contrast, pragmatic RCTs (pRCTs) test effectiveness in everyday practice with relatively unselected participants and under flexible conditions; in this way, pragmatic RCTs can "inform decisions about practice."
Another classification of RCTs categorizes them as "superiority trials", "noninferiority trials", and "equivalence trials", which differ in methodology and reporting.Most RCTs are superiority trials, in which one intervention is hypothesized to be superior to another in a statistically significant way. Some RCTs are noninferiority trials "to determine whether a new treatment is no worse than a reference treatment." Other RCTs are equivalence trials in which the hypothesis is that two interventions are indistinguishable from each other.
The advantages of proper randomization in RCTs include:
There are two processes involved in randomizing patients to different interventions. First is choosing a randomization procedure to generate an unpredictable sequence of allocations; this may be a simple random assignment of patients to any of the groups at equal probabilities, may be "restricted", or may be "adaptive." A second and more practical issue is allocation concealment, which refers to the stringent precautions taken to ensure that the group assignment of patients are not revealed prior to definitively allocating them to their respective groups. Non-random "systematic" methods of group assignment, such as alternating subjects between one group and the other, can cause "limitless contamination possibilities" and can cause a breach of allocation concealment.
However empirical evidence that adequate randomization changes outcomes relative to inadequate randomization has been difficult to detect.
The treatment allocation is the desired proportion of patients in each treatment arm.
An ideal randomization procedure would achieve the following goals:
However, no single randomization procedure meets those goals in every circumstance, so researchers must select a procedure for a given study based on its advantages and disadvantages.
This is a commonly used and intuitive procedure, similar to "repeated fair coin-tossing."Also known as "complete" or "unrestricted" randomization, it is robust against both selection and accidental biases. However, its main drawback is the possibility of imbalanced group sizes in small RCTs. It is therefore recommended only for RCTs with over 200 subjects.
To balance group sizes in smaller RCTs, some form of "restricted" randomization is recommended.The major types of restricted randomization used in RCTs are:
At least two types of "adaptive" randomization procedures have been used in RCTs, but much less frequently than simple or restricted randomization:
"Allocation concealment" (defined as "the procedure for protecting the randomization process so that the treatment to be allocated is not known before the patient is entered into the study") is important in RCTs.In practice, clinical investigators in RCTs often find it difficult to maintain impartiality. Stories abound of investigators holding up sealed envelopes to lights or ransacking offices to determine group assignments in order to dictate the assignment of their next patient. Such practices introduce selection bias and confounders (both of which should be minimized by randomization), possibly distorting the results of the study. Adequate allocation concealment should defeat patients and investigators from discovering treatment allocation once a study is underway and after the study has concluded. Treatment related side-effects or adverse events may be specific enough to reveal allocation to investigators or patients thereby introducing bias or influencing any subjective parameters collected by investigators or requested from subjects.
Some standard methods of ensuring allocation concealment include sequentially numbered, opaque, sealed envelopes (SNOSE); sequentially numbered containers; pharmacy controlled randomization; and central randomization.It is recommended that allocation concealment methods be included in an RCT's protocol, and that the allocation concealment methods should be reported in detail in a publication of an RCT's results; however, a 2005 study determined that most RCTs have unclear allocation concealment in their protocols, in their publications, or both. On the other hand, a 2008 study of 146 meta-analyses concluded that the results of RCTs with inadequate or unclear allocation concealment tended to be biased toward beneficial effects only if the RCTs' outcomes were subjective as opposed to objective.
The number of treatment units (subjects or groups of subjects) assigned to control and treatment groups, affects an RCT's reliability. If the effect of the treatment is small, the number of treatment units in either group may be insufficient for rejecting the null hypothesis in the respective statistical test. The failure to reject the null hypothesis would imply that the treatment shows no statistically significant effect on the treated in a given test. But as the sample size increases, the same RCT may be able to demonstrate a significant effect of the treatment, even if this effect is small.
An RCT may be blinded, (also called "masked") by "procedures that prevent study participants, caregivers, or outcome assessors from knowing which intervention was received."Unlike allocation concealment, blinding is sometimes inappropriate or impossible to perform in an RCT; for example, if an RCT involves a treatment in which active participation of the patient is necessary (e.g., physical therapy), participants cannot be blinded to the intervention.
Traditionally, blinded RCTs have been classified as "single-blind", "double-blind", or "triple-blind"; however, in 2001 and 2006 two studies showed that these terms have different meanings for different people.The 2010 CONSORT Statement specifies that authors and editors should not use the terms "single-blind", "double-blind", and "triple-blind"; instead, reports of blinded RCT should discuss "If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how."
RCTs without blinding are referred to as "unblinded","open", or (if the intervention is a medication) "open-label". In 2008 a study concluded that the results of unblinded RCTs tended to be biased toward beneficial effects only if the RCTs' outcomes were subjective as opposed to objective; for example, in an RCT of treatments for multiple sclerosis, unblinded neurologists (but not the blinded neurologists) felt that the treatments were beneficial. In pragmatic RCTs, although the participants and providers are often unblinded, it is "still desirable and often possible to blind the assessor or obtain an objective source of data for evaluation of outcomes."
The types of statistical methods used in RCTs depend on the characteristics of the data and include:
Regardless of the statistical methods used, important considerations in the analysis of RCT data include:
The CONSORT 2010 Statement is "an evidence-based, minimum set of recommendations for reporting RCTs."The CONSORT 2010 checklist contains 25 items (many with sub-items) focusing on "individually randomised, two group, parallel trials" which are the most common type of RCT.
For other RCT study designs, "CONSORT extensions" have been published, some examples are:
Two studies published in The New England Journal of Medicine in 2000 found that observational studies and RCTs overall produced similar results.The authors of the 2000 findings questioned the belief that "observational studies should not be used for defining evidence-based medical care" and that RCTs' results are "evidence of the highest grade." However, a 2001 study published in Journal of the American Medical Association concluded that "discrepancies beyond chance do occur and differences in estimated magnitude of treatment effect are very common" between observational studies and RCTs.
Two other lines of reasoning question RCTs' contribution to scientific knowledge beyond other types of studies:
Like all statistical methods, RCTs are subject to both type I ("false positive") and type II ("false negative") statistical errors. Regarding Type I errors, a typical RCT will use 0.05 (i.e., 1 in 20) as the probability that the RCT will falsely find two equally effective treatments significantly different.Regarding Type II errors, despite the publication of a 1978 paper noting that the sample sizes of many "negative" RCTs were too small to make definitive conclusions about the negative results, by 2005-2006 a sizeable proportion of RCTs still had inaccurate or incompletely reported sample size calculations.
Peer review of results is an important part of the scientific method. Reviewers examine the study results for potential problems with design that could lead to unreliable results (for example by creating a systematic bias), evaluate the study in the context of related studies and other evidence, and evaluate whether the study can be reasonably considered to have proven its conclusions. To underscore the need for peer review and the danger of over-generalizing conclusions, two Boston-area medical researchers performed a randomized controlled trial in which they randomly assigned either a parachute or an empty backpack to 23 volunteers who jumped from either a biplane or a helicopter. The study was able to accurately report that parachutes fail to reduce injury compared to empty backpacks. The key context that limited the general applicability of this conclusion was that the aircraft were parked on the ground, and participants had only jumped about two feet.
RCTs are considered to be the most reliable form of scientific evidence in the hierarchy of evidence that influences healthcare policy and practice because RCTs reduce spurious causality and bias. Results of RCTs may be combined in systematic reviews which are increasingly being used in the conduct of evidence-based practice. Some examples of scientific organizations' considering RCTs or systematic reviews of RCTs to be the highest-quality evidence available are:
Notable RCTs with unexpected results that contributed to changes in clinical practice include:
Many papers discuss the disadvantages of RCTs.Among the most frequently cited drawbacks are:
RCTs can be expensive;one study found 28 Phase III RCTs funded by the National Institute of Neurological Disorders and Stroke prior to 2000 with a total cost of US$335 million, for a mean cost of US$12 million per RCT. Nevertheless, the return on investment of RCTs may be high, in that the same study projected that the 28 RCTs produced a "net benefit to society at 10-years" of 46 times the cost of the trials program, based on evaluating a quality-adjusted life year as equal to the prevailing mean per capita gross domestic product.
The conduct of an RCT takes several years until being published, thus data is restricted from the medical community for long years and may be of less relevance at time of publication.
It is costly to maintain RCTs for the years or decades that would be ideal for evaluating some interventions.
Interventions to prevent events that occur only infrequently (e.g., sudden infant death syndrome) and uncommon adverse outcomes (e.g., a rare side effect of a drug) would require RCTs with extremely large sample sizes and may therefore best be assessed by observational studies.
Due to the costs of running RCTs, these usually only inspect one variable or very few variables, rarely reflecting the full picture of a complicated medical situation; whereas the case report, for example, can detail many aspects of the patient's medical situation (e.g. patient history, physical examination, diagnosis, psychosocial aspects, follow up).
A 2011 study done to disclose possible conflicts of interests in underlying research studies used for medical meta-analyses reviewed 29 meta-analyses and found that conflicts of interests in the studies underlying the meta-analyses were rarely disclosed. The 29 meta-analyses included 11 from general medicine journals; 15 from specialty medicine journals, and 3 from the Cochrane Database of Systematic Reviews. The 29 meta-analyses reviewed an aggregate of 509 randomized controlled trials (RCTs). Of these, 318 RCTs reported funding sources with 219 (69%) industry funded. 132 of the 509 RCTs reported author conflict of interest disclosures, with 91 studies (69%) disclosing industry financial ties with one or more authors. The information was, however, seldom reflected in the meta-analyses. Only two (7%) reported RCT funding sources and none reported RCT author-industry ties. The authors concluded "without acknowledgment of COI due to industry funding or author industry financial ties from RCTs included in meta-analyses, readers' understanding and appraisal of the evidence from the meta-analysis may be compromised."
Some RCTs are fully or partly funded by the health care industry (e.g., the pharmaceutical industry) as opposed to government, nonprofit, or other sources. A systematic review published in 2003 found four 1986–2002 articles comparing industry-sponsored and nonindustry-sponsored RCTs, and in all the articles there was a correlation of industry sponsorship and positive study outcome.A 2004 study of 1999–2001 RCTs published in leading medical and surgical journals determined that industry-funded RCTs "are more likely to be associated with statistically significant pro-industry findings." These results have been mirrored in trials in surgery, where although industry funding did not affect the rate of trial discontinuation it was however associated with a lower odds of publication for completed trials. One possible reason for the pro-industry results in industry-funded published RCTs is publication bias. Other authors have cited the differing goals of academic and industry sponsored research as contributing to the difference. Commercial sponsors may be more focused on performing trials of drugs that have already shown promise in early stage trials, and on replicating previous positive results to fulfill regulatory requirements for drug approval.
If a disruptive innovation in medical technology is developed, it may be difficult to test this ethically in an RCT if it becomes "obvious" that the control subjects have poorer outcomes—either due to other foregoing testing, or within the initial phase of the RCT itself. Ethically it may be necessary to abort the RCT prematurely, and getting ethics approval (and patient agreement) to withhold the innovation from the control group in future RCT's may not be feasible.
Historical control trials (HCT) exploit the data of previous RCTs to reduce the sample size; however, these approaches are controversial in the scientific community and must be handled with care.
Due to the recent emergence of RCTs in social science, the use of RCTs in social sciences is a contested issue. Some writers from a medical or health background have argued that existing research in a range of social science disciplines lacks rigour, and should be improved by greater use of randomized control trials.
Researchers in transport science argue that public spending on programmes such as school travel plans could not be justified unless their efficacy is demonstrated by randomized controlled trials.Graham-Rowe and colleagues reviewed 77 evaluations of transport interventions found in the literature, categorising them into 5 "quality levels". They concluded that most of the studies were of low quality and advocated the use of randomized controlled trials wherever possible in future transport research.
Dr. Steve Meliatook issue with these conclusions, arguing that claims about the advantages of RCTs, in establishing causality and avoiding bias, have been exaggerated. He proposed the following eight criteria for the use of RCTs in contexts where interventions must change human behaviour to be effective:
And the causal mechanisms:
RCTs are currently being used by a number of international development experts to measure the impact of development interventions worldwide. Development economists at research organizations including Abdul Latif Jameel Poverty Action Lab (J-PAL)and Innovations for Poverty Action have used RCTs to measure the effectiveness of poverty, health, and education programs in the developing world. While RCTs can be useful in policy evaluation, it is necessary to exercise care in interpreting the results in social science settings. For example, interventions can inadvertently induce socioeconomic and behavioral changes that can confound the relationships (Bhargava, 2008).
For some development economists, the main benefit to using RCTs compared to other research methods is that randomization guards against selection bias, a problem present in many current studies of development policy. In one notable example of a cluster RCT in the field of development economics, Olken (2007) randomized 608 villages in Indonesia in which roads were about to be built into six groups (no audit vs. audit, and no invitations to accountability meetings vs. invitations to accountability meetings vs. invitations to accountability meetings along with anonymous comment forms).After estimating "missing expenditures" (a measure of corruption), Olken concluded that government audits were more effective than "increasing grassroots participation in monitoring" in reducing corruption. Overall, it is important in social sciences to account for the intended as well as the unintended consequences of interventions for policy evaluations.
A 2005 review found 83 randomized experiments in criminology published in 1982-2004, compared with only 35 published in 1957-1981.The authors classified the studies they found into five categories: "policing", "prevention", "corrections", "court", and "community". Focusing only on offending behavior programs, Hollin (2008) argued that RCTs may be difficult to implement (e.g., if an RCT required "passing sentences that would randomly assign offenders to programmes") and therefore that experiments with quasi-experimental design are still necessary.
RCTs have been used in evaluating a number of educational interventions. Between 1980 and 2016, over 1,000 reports of RCTs have been published.For example, a 2009 study randomized 260 elementary school teachers' classrooms to receive or not receive a program of behavioral screening, classroom intervention, and parent training, and then measured the behavioral and academic performance of their students. Another 2009 study randomized classrooms for 678 first-grade children to receive a classroom-centered intervention, a parent-centered intervention, or no intervention, and then followed their academic outcomes through age 19.
Mock randomised controlled trials, or simulations using confectionery, can conducted in the classroom to teach students and health professionals the principles of RCT design and critical appraisal.
A 2017 review of the 10 most cited randomised controlled trials noted poor distribution of background traits, difficulties with blinding, and discussed other assumptions and biases inherent in randomised controlled trials. These include the "unique time period assessment bias", the "background traits remain constant assumption", the "average treatment effects limitation", the "simple treatment at the individual level limitation", the "all preconditions are fully met assumption", the "quantitative variable limitation" and the "placebo only or conventional treatment only limitation".
Evidence-based medicine (EBM) is an approach to medical practice intended to optimize decision-making by emphasizing the use of evidence from well-designed and well-conducted research. Although all medicine based on science has some degree of empirical support, EBM goes further, classifying evidence by its epistemologic strength and requiring that only the strongest types can yield strong recommendations; weaker types can yield only weak recommendations. The term was originally used to describe an approach to teaching the practice of medicine and improving decisions by individual physicians about individual patients. Use of the term rapidly expanded to include a previously described approach that emphasized the use of evidence in the design of guidelines and policies that apply to groups of patients and populations. It has subsequently spread to describe an approach to decision-making that is used at virtually every level of health care as well as other fields.
Cochrane is a British charity formed to organise medical research findings so as to facilitate evidence-based choices about health interventions faced by health professionals, patients, and policy makers. Cochrane includes 53 review groups that are based at research institutions worldwide. Cochrane has approximately 30,000 volunteer experts from around the world.
A cohort study is a particular form of longitudinal study that samples a cohort, performing a cross-section at intervals through time. While a cohort study is a panel study, a panel study is not always a cohort study as individuals in a panel study do not always share a common characteristic.
Publication bias is a type of bias that occurs in published academic research. It occurs when the outcome of an experiment or research study influences the decision whether to publish or otherwise distribute it. Publishing only results that show a significant finding disturbs the balance of findings, and inserts bias in favor of positive results. The study of publication bias is an important topic in metascience.
A hierarchy of evidence is a heuristic used to rank the relative strength of results obtained from scientific research. There is broad agreement on the relative strength of the principal types of epidemiological studies but no single, universally-accepted hierarchy of evidence. More than 80 different hierarchies have been proposed for assessing medical evidence. The design of the study and the endpoints measured affect the strength of the evidence. Typically, systematic reviews and meta-analysies rank most highly, randomized controlled trials (RCTs) rank above observational studies, while expert opinion and anecdotal experience are ranked at the bottom. Evidence hierarchies are often applied in evidence-based practices and are integral to evidence-based medicine (EBM).
An intention-to-treat (ITT) analysis of the results of an experiment is based on the initial treatment assignment and not on the treatment eventually received. ITT analysis is intended to avoid various misleading artifacts that can arise in intervention research such as non-random attrition of participants from the study or crossover. ITT is also simpler than other forms of study design and analysis because it does not require observation of compliance status for units assigned to different treatments or incorporation of compliance into the analysis. Although ITT analysis is widely employed in published clinical trials, it can be incorrectly described and there are some issues with its application. Furthermore, there is no consensus on how to carry out an ITT analysis in the presence of missing outcome data.
In a randomized experiment, an allocation concealment strategy hides the method of sorting trial participants into treatment groups so that this knowledge cannot be exploited. Adequate allocation concealment serves to prevent study participants from choosing treatment allocations for subjects. Studies with poor allocation concealment are prone to selection bias.
In epidemiology, reporting bias is defined as "selective revealing or suppression of information" by subjects. In artificial intelligence research, the term reporting bias is used to refer to people's tendency to under-report all the information available.
CONSORT encompasses various initiatives developed by the CONSORT Group to alleviate the problems arising from inadequate reporting of randomized controlled trials. It is part of the larger EQUATOR Network initiative to enhance the transparency and accuracy of reporting in research.
Treatment of chronic fatigue syndrome (CFS) is variable and uncertain, and the condition is primarily managed rather than cured.
Open peer review is a process in which names of peer reviewers of papers submitted to academic journals are disclosed to the authors of the papers in question. In some cases, as with the BMJ and BioMed Central, the process also involves posting the entire pre-publication history of the article online, including not only signed reviews of the article, but also its previous versions and author responses to the reviewers.
The Jadad scale, sometimes known as Jadad scoring or the Oxford quality scoring system, is a procedure to independently assess the methodological quality of a clinical trial. It is named after Colombian physician Alex Jadad who in 1996 described a system for allocating such trials a score of between zero and five (rigorous). It is the most widely used such assessment in the world, and as of 2019, its seminal paper has been cited in over 15,000 scientific works.
Sham surgery is a faked surgical intervention that omits the step thought to be therapeutically necessary.
Critical appraisal is the use of explicit, transparent methods to assess the data in published research, applying the rules of evidence to factors such as internal validity, adherence to reporting standards, conclusions and generalizability. Critical appraisal methods form a central part of the systematic review process. They are used in evidence-based healthcare training to assist clinical decision-making, and are increasingly used in evidence-based social care and education provision.
A cluster randomised controlled trial is a type of randomised controlled trial in which groups of subjects are randomised. Cluster randomised controlled trials are also known as cluster randomised trials, group-randomised trials, and place-randomized trials.
George Lewith was a professor at the University of Southampton researching alternative medicine and a practitioner of complementary medicine. He was a prominent and sometimes controversial advocate of complementary medicine in the UK.
Renal sympathetic denervation (RSDN), is a minimally invasive, endovascular catheter based procedure using radiofrequency ablation or ultrasound ablation aimed at treating resistant hypertension. Nerves in the wall of the renal artery are ablated by applying radiofrequency pulses or ultrasound to the renal arteries. This causes reduction of sympathetic afferent and efferent activity to the kidney and blood pressure can be decreased. Early data from international clinical trials without sham controls was promising - demonstrating large blood pressure reductions in patients with treatment-resistant hypertension. However, in 2014 a prospective, single-blind, randomized, sham-controlled clinical trial failed to confirm a beneficial effect on blood pressure. A 2014 consensus statement from The Joint UK Societies did not recommend the use of renal denervation for treatment of resistant hypertension on current evidence.
A stepped-wedge trial is a type of randomised controlled trial, a scientific experiment which is structured to reduce bias when testing new medical treatments, social interventions, or other testable hypotheses. In a traditional RCT, a part of the participants in the experiment are simultaneously and randomly assigned to a group that receives the treatment and another part to a group that does not. In an SWT, typically a logistical constraint prevents the simultaneous treatment of some participants, and instead, all or most participants receive the treatment in waves or "steps".
Allegiance bias in behavioral sciences is a bias resulted from the investigator's or researcher's allegiance to a specific school of thought.
Ronald A. Fisher was "interested in application and in the popularization of statistical methods and his early book Statistical Methods for Research Workers , published in 1925, went through many editions and motivated and influenced the practical use of statistics in many fields of study. His Design of Experiments (1935) [promoted] statistical technique and application. In that book he emphasized examples and how to design experiments systematically from a statistical point of view. The mathematical justification of the methods described was not stressed and, indeed, proofs were often barely sketched or omitted altogether ..., a fact which led H. B. Mann to fill the gaps with a rigorous mathematical treatment in his well known treatise, Mann (1949)."Page 87: Conniffe, Denis (1990–1991). "R. A. Fisher and the development of statistics—a view in his centenary year". Journal of the Statistical and Social Inquiry Society of Ireland. XXVI (3). Dublin: Statistical and Social Inquiry Society of Ireland. pp. 55–108. ISSN 0081-4776.