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A brief history of the randomized controlled trial. From oranges and lemons to the gold standard
Abstract
This article discusses the history and development of randomized clinical trial methodology, the reasons for its status and authority as a method of therapeutic evaluation, and the continuing role of clinical judgement in designing, interpreting, and applying the findings of trials.
... J. Burns Amberson decyzję o przydzieleniu jednego z 24 pacjentów do konkretnej grupy podejmował po rzucie monetą. Badania te nie spełniały jednak wszystkich norm rzetelnie zaprojektowanych klinicznych badań randomizowanych (12). W 1937 roku Austin Bradford Hill opublikował serię artykułów poświęconych statystyce w medycynie, w których zachęcał do zastosowania w badaniach medycznych metody randomizacji, opisanej przez uprzednio przez Fishera. ...
... Badacze opisali zasady projektowania wiarygodnych testów klinicznych, wprowadzając przy tym elementy współczesnych badań randomizowanych z grupą kontrolną. Należały do nich: losowy dobór grupy, zaślepienie, a także procedury wprowadzające losowy sposób przydzielenia badanych jednostek do grupy (12). W 1946 roku Feldman wygłaszał wykłady w Wielkiej Brytanii, przedstawiając wyniki swoich badań nad streptomycyną na zwierzętach. ...
... O ile w badaniu obserwacyjnym trudno wyodrębnić taki czynnik, ponieważ towarzyszą mu różnorakie zmienne zakłócające, o tyle przy losowym przydziale do grup randomizowanych zmienne te rozłożone są podobnie w obu grupach, co pozwala na wyodrębnienie wartości zmiennej niezależnej -czynnika, który zamierzamy badać. Główną zasadą towarzyszącą modelowi, w oparciu o który projektuje się badania randomizowane, jest zestawienie w określonych i kontrolowanych warunkach co najmniej dwóch reżimów terapeutycznych (jednym z nich jest komparator -standardowa terapia, placebo bądź wykluczenie aktywnej terapii, drugim -badane zjawisko) (12). ...
Synopsis
1. Wprowadzenie. Zagadnienie sprawiedliwości w etyce badań biomedycznych
2. Złoty standard. Kliniczne badania randomizowane (RCT) w medycynie
3. Medycyna oparta na dowodach (EBM)
4. Poziomy wiarygodności wyników badań w biomedycynie
5. Praktyka medyczna a badanie naukowe. Problematyka powinności terapeutycznej
6. Między wiarygodnością a sprawiedliwością: zasada równowagi (equipoise)
7. Dyskusje wokół zasady równowagi
8. Adaptacyjne badania kliniczne (outcome-adaptive trials)
8.1. Badana randomizowane pozaustrojowego utlenowania krwi (ECMO)
8.2. Adaptacyjne badania kliniczne – sprawiedliwy podział ryzyka i korzyści a efektywność
9. Podsumowanie
10. Literatura
... In order to gauge the practicality of using the framework to aid researchers in examining telemedicine satisfaction evaluations, a pilot study was conducted. Pilot studies are considered an appropriate first step for testing the adequacy of research tools and analysis techniques [53]. ...
... For example, RCTs were more likely than other studies to include information about the quality of the instruments used. This could reflect the more stringent reporting requirements of these types of studies [53] and provide additional for researchers attempting to understand deficiencies in reporting on methodologies [15]. ...
Stakeholder satisfaction is often considered a key to the success of telemedicine systems. However, it can be difficult to understand and compare satisfaction evaluations because of variations in reporting and study designs. This research will contribute to the knowledge by developing a conceptual framework around key concepts that relate to understanding studies on telemedicine satisfaction. The framework is built based on a developmental review of the telemedicine and telehealth literature obtained from searches of PubMed and Google Scholar. Using a conceptual matrix, researchers have synthesized the results into a framework that includes: satisfaction dimensions, stakeholders, type of care, type of system, context and methodologies. This research expands these concepts by discussing attributes of each and tests the framework by conducting a pilot study that identifies the concepts in primary study sources. The results of the framework and the pilot study are reported.
... Randomised control trials are often held up as the "gold standard" for treatment effects, particularly in the health sciences [35]. While such experiments are possible in transport, as with the Metropolitan Transit Authority (MTA) experiments in Boston conducted in the early 1960s [36], they remain rare [37]. ...
... 35: BART boardings, observed vs. RegARIMA model ...
This research combines several large, continuously collected data sets to understand recent travel demand trends in San Francisco, and it develops a tool for measuring transport project impacts.
Because they are continuously collected, these data provide an opportunity to measure change in a way that is not available in traditional, cross-sectional travel surveys. The data used are from San Francisco and cover performance of the transit system and associated factors expected to drive transit demand.
This study employs a two stage methodology to derive insight from these data. First, a performance monitoring tool is developed to process the raw data and report meaningful performance indicators. This tool encapsulates the necessary data cleaning functionality, and manages a multi-stage data expansion process to ensure that data are representative of the system as a whole. Second, time series models of transit ridership are estimated from the outputs of the performance monitoring tool. These time series models provide a means of quantifying the portion of the ridership changes due to service changes versus background factors, such as employment growth.
The estimated models are applied to understand the drivers of recent ridership trends in the San Francisco, where ridership on the MUNI bus system remains flat in spite of population and employment growth, while ridership on the BART system grows faster than employment. In addition, the models are applied to several planning case studies, including both ex-post ridership evaluations and short-term forecasting applications.
The outcome of this research is to establish and test a tool to facilitate the use of passively collected data for retrospective travel demand analyses. It provides insight into the effects of transport projects, and lays the groundwork for a future studies that further our ability to observe and understand travel behaviour.
... Randomized Control Trials (RCTs) are considered a gold standard in determining whether a causal relationship exists between a specific intervention and observed outcome [41]. Traditional RCTs operate across groups with each group receiving a different experimental condition, and are unable to provide individual insights [42]. ...
... The productivity scores on Days 21, 25, 26, and 27 (days when the participant achieved the target sleep duration: 6.5 h) would be averaged and form the Stage 2 productivity score (i.e., productivity when sleep duration is 6.5 h) since during those days the participant was able to adjust their sleep behavior to the target goal of 6.5 h of sleep. Similarly, Days 39,41,42, and 44 would be averaged to form the Stage 3 productivity score (i.e., productivity when sleep duration is 8.5 h) and, if Stage 4 were completed, the days where the sleep duration was in the target range would be used to compute the average productivity for 7.5 h of sleep. These four scores (baseline and Stages 2-4) would then be compared to determine the highest productivity. ...
Smartphones and wearable sensors have enabled unprecedented data collection, with many products now providing feedback to users about recommended step counts or sleep durations. However, these recommendations do not provide personalized insights that have been shown to be best suited for a specific individual. A scientific way to find individualized recommendations and causal links is to conduct experiments using single-case experimental design; however, properly designed single-case experiments are not easy to conduct on oneself. We designed, developed, and evaluated a novel platform, QuantifyMe, for novice self-experimenters to conduct proper-methodology single-case self-experiments in an automated and scientific manner using their smartphones. We provide software for the platform that we used (available for free on GitHub), which provides the methodological elements to run many kinds of customized studies. In this work, we evaluate its use with four different kinds of personalized investigations, examining how variables such as sleep duration and regularity, activity, and leisure time affect personal happiness, stress, productivity, and sleep efficiency. We conducted a six-week pilot study (N = 13) to evaluate QuantifyMe. We describe the lessons learned developing the platform and recommendations for its improvement, as well as its potential for enabling personalized insights to be scientifically evaluated in many individuals, reducing the high administrative cost for advancing human health and wellbeing.
... The scientific community regards the randomised controlled trial (RCT) as the gold standard for establishing efficacy of a treatment or intervention [12]. Ideally a large, double-blind multicentre study, the RCT's strength lies in rigorously eliminating bias. ...
... Indeed, RCTs are touted as the gold standard of experimental research (Jadad and Enkin 2008;Meldrum 2000). A principal reason for this acclaim is because they employ a deductive methodology-a causal inference may be implied if the assumptions of the method are met (Cartwright 2007, p. 11). ...
Such is the grip of formal methods of statistical inference—that is, frequentist methods for generalizing from sample to population in enumerative studies—in the drawing of scientific inferences that the two are routinely deemed equivalent in the social, management, and biomedical sciences. This, despite the fact that legitimate employment of said methods is difficult to implement on practical grounds alone. But supposing the adoption of these procedures were simple does not get us far; crucially, methods of formal statistical inference are ill-suited to the analysis of much scientific data. Even findings from the claimed gold standard for examination by the latter, randomized controlled trials, can be problematic.
Scientific inference is a far broader concept than statistical inference. Its authority derives from the accumulation, over an extensive period of time, of both theoretical and empirical knowledge that has won the (provisional) acceptance of the scholarly community. A major focus of scientific inference can be viewed as the pursuit of significant sameness, meaning replicable and empirically generalizable results among phenomena. Regrettably, the obsession with users of statistical inference to report significant differences in data sets actively thwarts cumulative knowledge development.
The manifold problems surrounding the implementation and usefulness of formal methods of statistical inference in advancing science do not speak well of much teaching in methods/statistics classes. Serious reflection on statistics' role in producing viable knowledge is needed. Commendably, the American Statistical Association is committed to addressing this challenge, as further witnessed in this special online, open access issue of The American Statistician.
... Therefore, studies that can provide goodquality evidence are required by stakeholders for clinical decision making. For healthcare professionals and policy makers, the randomized controlled trial (RCT) among all forms of controlled studies is regarded as the "gold standard" to attest to the efficacy of a healthcare intervention (Meldrum, 2000;Moher et al., 2001;Silverman, 2009). ...
Guidelines for clinical trials of acupuncture are scarce, particularly in their guidance on choosing an adequate control in an acupuncture trial. This guideline was developed to address the research methodology for clinical research in acupuncture which contains the essential elements to be considered in the design, preparation and reporting of an acupuncture RCT. Particularly, investigators focused on the control design because of the unique feature of acupuncture. As one size does not fit all, one single design cannot answer all research questions. Therefore, we recommend that the clinical questions be answered in different stages of trials by choosing the appropriate control or comparator. This concept is adapted from classical drug trials developed by the Food and Drug Administration (FDA) of USA in which trials are staged in four phages in order to address different research questions. From the points listed above, this guideline offers the specific recommendations in an acupuncture RCT.
... Randomized clinical trials (RCT) are considered the gold standard (4) for generating data to prove the efficacy, safety, and tolerability of a new therapy (5,6). Developing new therapies and conducting high-quality RCT is expensive and resource-demanding (7). ...
Objective:
Advanced therapy medicinal products (ATMPs) constitute a class of innovative products that encompasses gene therapy, somatic cell therapy, and tissue-engineered products (TEP). There is an increased investment of commercial and non-commercial sponsors in this field and a growing number of ATMPs randomized clinical trials (RCT) and patients enrolled in such trials. RCT generate data to prove the efficacy of a new therapy, but the discontinuation of RCTs wastes scarce resources. Our objective is to identify the number and characteristics of discontinued ATMPs trials in order to evaluate the rate of discontinuation.
Methods:
We searched for ATMPs trials conducted between 1999 to June 2015 using three databases, which are Clinicaltrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the EU Drug Regulating Authorities Clinical Trials (EudraCT). We selected the ATMPs trials after elimination of the duplicates. We identified the disease areas and the sponsors as commercial or non-commercial organizations. We classified ATMPs by type and trial status, that is, ongoing, completed, terminated, discontinued, and prematurely ended. Then, we calculated the rate of discontinuation.
Results:
Between 1999 and June 2015, 143 withdrawn, terminated, or prematurely ended ATMPs clinical trials were identified. Between 1999 and June 2013, 474 ongoing and completed clinical trials were identified. Therefore, the rate of discontinuation of ATMPs trials is 23.18%, similar to that for non-ATMPs drugs in development. The probability of discontinuation is, respectively, 27.35, 16.28, and 16.34% for cell therapies, gene therapies, and TEP. The highest discontinuation rate is for oncology (43%), followed by cardiology (19.2%). It is almost the same for commercial and non-commercial sponsors; therefore, the discontinuation reason may not be financially driven.
Conclusion:
No failure risk rate per development phase is available for ATMPs. The discontinuation rate may prove helpful when assessing the expected net present value to support portfolio arbitration and may be considered by patients and potential investigators in their decisions to participate in ATMP trials. These results carry limitation because the rationale for discontinuation is unknown. Further research about the reasons of discontinuation and the risk of negative results is needed to inform stakeholders.
... Such trials are the gold standard in editing clinical trials whereby individuals are randomized to either intervention or control groups. 49 It is important to present results of cost-effectiveness analyses in a transparent way, while exploring the uncertainty in key parameters and pay attention to validating the model and the model outcomes. 50 In the current study, the uncertainty was addressed using one-way sensitivity analyses and probabilistic sensitivity analyses. ...
Objectives:
The aim was to examine the health and economic consequences of osteopathic care for low back pain and neck pain in addition to usual care compared to usual care alone.
Design:
A decision tree model considering a one-year time horizon was applied. The analysis occurred from a health insurance perspective only considering direct medical costs. The health effects were expressed as quality-adjusted life years (QALYs).
Main outcomes:
The main outcome was the incremental cost-effectiveness ratio (ICER). The uncertainty around key input parameters was addressed applying one-way and probabilistic sensitivity analyses (5000 simulations).
Results:
For low back pain, osteopathy resulted in cost savings (€385.1 vs €501.8/patient) at improved QALYs (0.666 vs. 0.614) compared to usual care. For neck pain, osteopathy resulted in additional costs (€577.3 vs. €521.0) and improved QALYs (0.639 vs. 0.609) resulting in an ICER of €1,870/QALY. The one-way sensitivity analysis identified the hospitalization cost (back) and osteopathy cost (neck) as major cost drivers. The probabilistic sensitivity analysis resulted in an average net saving of €163 (95%CI-€260, -€49.1) and a QALY gain of 0.06 (95%CI -0.06, 0.17) for low back pain and an average additional cost of €55.1 (95%CI €20.9, €129) and improved QALY gain of 0.03 (95%CI-0.06, 0.12) for neck pain.
Conclusions:
Osteopathy was found to be a 'dominant' (low back pain) and cost-effective strategy (neck pain) compared to usual care. Further health economic evaluation studies considering a broader range of cost items and longer time horizon are required.
... In contrast with the new conventional drugs, their constraining legislative measures framing market approvals are not built upon the same basis. The FDA requires conventional drugs to have proven both their efficacy and their safety before being released on the market, notably by implementing randomised control trials (RCTs) (Bothwell and Podolsky 2016;Meldrum 2000). 8 D/HS are governed by a hybrid regime sliding almost in between food and drugs (Chen 2009: 79-91). ...
In this chapter, we present a specific aspect of our socio-anthropological research focusing on the federal institutionalisation of CAM in the USA: the case of ‘dietary and herbal supplements’ (D/HS). We show how the case provides a good example of different and specific configurations of medical research on CAM since the 1990s through the creation of three federal entities. Based on an analysis of controversies and challenges around specific ‘D/HS’, we interrogate the manners in which a plurality of federal and non-federal agents involved in this mixed social space collaborates and competes on the medical evaluation of CAM—particularly around ideas of efficacy, safety, authenticity, and integration—shaping and re-shaping the places they assign to CAM within the broader American health system.
... While there have been previous meta-analysis of studies comparing CB with RF treatment, this analysis is the first to include only RCTs, which is still considered to be the 'gold standard' for clinical trials [25]. ...
Objective:
The aim of this study was to evaluate the clinical efficacy and safety outcomes of the treatment with cryoballoon (CB) compared to the treatment with traditional irrigated radiofrequency ablation (RF) for pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (pAF) and refractory to antiarrhythmic drug therapy (AAD).
Design:
We conducted a systemic review to find and include more than two randomized controlled trials (RCTs) with at least 20 patients in each of the CB and RF groups. Thereafter, we performed a meta-analysis to compare the treatment with CB and RF in primary outcomes including 1 year free from AF, complications and re-ablation procedures. Additionally, we evaluated procedure time and fluoroscopy duration in both groups. Risk of bias in the individual studies and across studies was assessed using Cochrane methods.
Data extraction and synthesis:
Two reviewers extracted study data and assessed risk of bias. Primary outcome data were extracted from the time point 1 year after the procedure. The random-effects model was used to calculate the odds ratio with 95% confidence interval.
Data sources:
Data sources utilized were PubMed and CENTRAL databases up to 16 June 2016.
Eligibility criteria for selecting studies:
Included studies were RCTs in adults with pAF and refractory to AAD in which CB therapy, including 1st and 2nd generation CB, was compared to the traditional irrigated RF therapy. Clinical outcomes assessed in each RCT were 1 year AF-free survival, complication rates, re-ablations, fluoroscopy time and procedure time.
Results:
The systematic review identified four randomized controlled trials that reported on comparative clinical outcomes involving 1284 patients. Our meta-analysis demonstrated that CB ablation had a non-significant higher success rate than RF therapy (OR 1.13; 95% CI 0.72-1.77). However, our study showed a relatively higher rate of complications in the CB group (OR 1.20; 95% CI 0.58-2.52). Furthermore, CB treatment was associated with a non-significant, shorter procedure time and marginally prolonged fluoroscopy time in comparison to RF treatment.
Conclusion:
Our systemic review and meta-analysis revealed further evidence that cryoballoon ablation is an equally effective alternative procedure to the standard radiofrequency treatment with a slightly, non-significant higher freedom from AF 1 year after the ablation and a shorter procedure time.
... Randomized controlled trial (RCT) is the best design available in biomedical research [1]. Randomization eliminates confounding variables and enables RCT to pinpoint the cause of a disease [2]. ...
Background:
The quality of randomized controlled trials from Saudi Arabia is unknown since most are observational studies.
Objective:
To determine (1) the quantity and quality of randomized controlled trials published from Saudi Arabia, and (2) whether significance of intervention effect varied by study quality.
Methods:
PubMed, SCOPUS, and Cochrane were searched with keywords for trials published from Saudi Arabia until February 2018. A total of 422 records were identified and screened, resulting in 61 eligible trials for analysis. Two researchers abstracted trial characteristics and assessed quality in seven domains (randomization, allocation concealment, blinding of assessors or participants, incomplete outcome data, selective reporting, and other sources of bias) using the Cochrane Collaboration Risk of Bias Tool.
Results:
A majority of the trials (57%) were published during 2010-2018. High risk of bias was present for blinding (outcome: 13%; participants and personnel: 28%). Biases could not be assessed due to lack of information (unclear risk) in the domains of randomization (54%), allocation concealment (44%), and blinding of outcome assessment (57%). When all seven domains were considered together (summary risk of bias), 0% of the trials had low risk, 39% had high risk, and 61% had unclear risk of biases. A greater proportion of high-risk trials had significant intervention effect than unclear-risk trials (79% vs. 67%).
Conclusion:
The volume and quality of trials in Saudi Arabia was low. More high-quality randomized controlled trials are warranted to address chronic diseases.
... This thesis has some specific strengths worth mentioning. First, all outcome studies were randomized controlled studies, considered the gold standard for clinical research (Meldrum, 2000). Another strength is the use of a diagnostic procedure in all studies, making sure that all included patients fulfilled the criteria for MDD. ...
Depression is a debilitating disorder that affects a large part of the adult population every year. Yet there is still a lack of access to effective care for people in need. Cognitive Behaviour therapy (CBT) is an evidence-based method for treating depression that together with the increased availability of Internet services provides an opportunity to increase access to effective treatment. Internet-based interventions can be effective in the treatment of depression, but there is a lack of knowledge concerning which formats of delivery that can be used and if therapeutic alliance is of equal importance when providing treatment over the Internet. The overall aim of this thesis was to examine the effects of different treatment formats (email therapy, guided self-help, and blended treatment) in internet-based CBT for depression and to further examine the role of alliance in these treatment modalities.
Findings from this thesis show that email therapy and internet-based treatment programs were effective methods for treating depression. Alliance ratings were high, showing that a positive therapeutic alliance can be achieved in internet-based treatments. Patient-rated alliance could not predict outcome in any of the different treatment formats. However, therapist-rated alliance predicted change in depression during blended treatment. This thesis includes the first randomized controlled study on CBT-based email therapy, and the first internet-based behavioral activation program with ACT-components, for adult depression.
... The randomized controlled trial (RCT) is critical to exploring the impact of interventions and is the ideal study design to establish causality [1]. Unique to the RCT design is the random assignment of participants to a treatment or intervention group, which reduces the potential for systematic biases that may compromise internal validity in observational epidemiologic studies [2]. RCTs have been critical to advancing public health and clinical research; many important medical treatments such as the wellknown HIV drug, Tenofovir, have only been approved for population-wide use after a long series of RCTs [3]. ...
Background
The conduct of randomized controlled trials (RCTs) in low-resource settings may present unique financial, logistic, and process-related challenges. Middle-income countries that have comparable disease burdens to low-income countries, but greater availability of resources, may be conducive settings for RCTs. Indeed, the country of Botswana is experiencing a rapid increase in the conduct of RCTs. Our objective was to explore the experiences of individuals conducting RCTs in Botswana to gain an understanding of the challenges and adaptive strategies to their work.
Methods
We conducted in-depth interviews with 14 national and international individuals working on RCTs in Botswana. Participants included principal investigators, research coordinators, lab technicians, research assistants, and other healthcare professionals. Interviews were audiotaped, transcribed verbatim, and coded for thematic analysis.
Results
Five primary themes were identified: ethics board relationships (including delays in the process); research staff management (including staff attrition and career development); study recruitment and retention (including the use of reimbursements); resource availability (including challenges accessing laboratory equipment); and capacity-building (including issues of exporting locally sourced samples). These themes were explored to discuss key challenges and adaptive strategies.
Conclusions
This study offers a first-hand account of individuals engaged in conducting RCTs in Botswana, a nation that is experiencing a rapid increase in research activities. Findings provide a foundational understanding for researchers in Botswana and trial managers in similar settings when planning RCTs so that the conduct of research does not outpace the ability to manage, support, and regulate it.
... In addition, the opportunity to use an adaptive trial design that is potentially able to reduce the number of patients to be included in drug trials should be considered, although not frequently used in neonatology until now. [14,15] Randomized controlled trials (RCT) remain the gold standard for drug evaluation [16,17] but they are challenging and even more is the use of a placebo, required in the absence of a reference validated drug to be used as comparator. ...
Background
Despite specific initiatives and identified needs, most neonatal drugs are still used off-label, with variable dosage administrations and schedules. In high risk preterm and term neonates, drug evaluation is challenging and randomized controlled trials (RCT) are difficult to conduct and even more is the use of a placebo, required in the absence of a reference validated drug to be used as comparator.
Methods
We analyzed the complete ClinicalTrials.gov registry 1) to describe neonatal RCT involving a placebo, 2) to report on the medical context and ethical aspects of placebo use.
Results
Placebo versus drug RCT (n = 146), either prevention trials (n = 57, 39%) or therapeutic interventions (n = 89, 61%), represent more than a third of neonatal trials registered in the National Institute of Health clinical trial database (USA) since 1999. They mainly concerned preterm infants, evaluating complications of prematurity. Most trials were conducted in the USA, were single centered, and funded by non-profit organizations. For the three top drug trials evaluating steroids (n = 13, 9.6%), erythropoietin (EPO, n = 10, 6.8%) and nitric oxide (NO, n = 9, 6.2%), the objectives of the trial and follow-up were analyzed in more details.
Conclusion
Although a matter of debate, the use of placebo should be promoted in neonates to evaluate a potential new treatment, in the absence of reference drug. Analysis of the trials evaluating steroids showed that long-term follow-up of exposed patients, although required by international guidelines, is frequently missing and should be planned to collect additional information and optimize drug evaluation in these high-risk patients.
... To assist IBS patients in determining their individualized food triggers, TummyTrials uses a single-case experimental design. This design contrasts group randomized controlled trials (RCTs), where participants are randomly assigned to a treatment or control condition [48]. RCTs are considered the highest level of clinical efficacy evaluation for an intervention, but the population-based estimates they produce do not inform how a specific individual and their symptoms will respond [60]. ...
Diagnostic self-tracking, the recording of personal information to diagnose or manage a health condition, is a common practice, especially for people with chronic conditions. Unfortunately, many who attempt diagnostic self-tracking have trouble accomplishing their goals. People often lack knowledge and skills needed to design and conduct scientifically rigorous experiments, and current tools provide little support. To address these shortcomings and explore opportunities for diagnostic self-tracking, we designed, developed, and evaluated a mobile app that applies a self-experimentation framework to support patients suffering from irritable bowel syndrome (IBS) in identifying their personal food triggers. TummyTrials aids a person in designing, executing, and analyzing self-experiments to evaluate whether a specific food triggers their symptoms. We examined the feasibility of this approach in a field study with 15 IBS patients, finding that participants could use the tool to reliably undergo a self-experiment. However, we also discovered an underlying tension between scientific validity and the lived experience of self-experimentation. We discuss challenges of applying clinical research methods in everyday life, motivating a need for the design of self-experimentation systems to balance rigor with the uncertainties of everyday life.
... RCTs are generally recognized as the gold standard for the efficacy of clinical interventions by excluding the non-specific effect via a placebo control 126 . However, one study reported that the effect of EA therapy was merely the non-specific effect 63 . ...
Sham electroacupuncture (EA) control is commonly used to evaluate the specific effects of EA in randomized-controlled trials (RCTs). However, establishing an inert and concealable sham EA control remains methodologically challenging. Here, we aimed to systematically investigate the sham EA methods. Eight electronic databases were searched from their inception to April 2015. Ten out of the 17 sham EA methods were identified from 94 RCTs involving 6134 participants according to three aspects: needle location, depth of needle insertion and electrical stimulation. The top three most frequently used types were sham EA type A, type L and type O ordinally. Only 24 out of the 94 trials reported credibility tests in six types of sham EA methods and the results were mainly as follows: sham EA type A (10/24), type B (5/24) and type Q (5/24). Compared with sham EA controls, EA therapy in about 56.2% (59/105 trials) trials reported the specific effects, of which, the highest positive rate was observed in type N (3/4), type F (5/7), type D (4/6) and type M (2/3). In conclusion, several sham EA types were identified as a promising candidate for further application in RCTs. Nonetheless, more evidence for inert and concealable sham EA control methods is needed.
... Είναι η έρευνα εκείνη που προωθεί την επιστήμη της Φυσικοθεραπείας πέρα από τα αποδεκτά καθημερινά όρια και προάγει την τεκμηριωμένη φυσικοθεραπευτική πρακτική. Η αρχή της επιστημονικής απόδειξης χρησιμοποιείται από παλιά (Meldrum, 2000). Γιατί όμως να χρειάζεται απόδειξη μία φυσικοθεραπευτική πράξη όταν παρατηρεί ο φυσικοθεραπευτής σαφή κλινική βελτίωση στους 1 World Confederation for Physical Therapy. ...
... An interventional study that uses the randomized controlled trial (RCT) design produces the most unbiased estimate on the efficacy of the intervention; and it does so through the control of confounding factors and minimization of bias. 17 Unfortunately, the current evidence points to inadequate research, both in terms of quantity and quality, from Arab Gulf States. Bibliometric indicators (e.g. ...
The leading chronic conditions in Arab Gulf States are modifiable by lifestyle change. Available evidence suggests a paucity of experimental studies on these conditions. We aimed to review the published randomized controlled trials on behavioral modification in the Arab Gulf States. Three databases (PubMed, Embase, and Cochrane) were searched for related keywords, and the records were screened for eligible studies; data were abstracted on trial characteristics (e.g. publication year, study population, primary outcome, intervention, control, follow-up, and outcome results), and a quality assessment of the trials was made. A total of 16 trials were eligible; 50% did not provide sample size calculation, and 31% did not designate a primary outcome. A majority of the trials did not explain randomization or allocation concealment (50%), did not blind outcome assessors (69%) or adopt an intention-to-treat analysis (56%); and 82% of trials found a significant intervention effect. More behavioral trials should be conducted overall and specifically for conditions for which there are no trials (e.g. respiratory tract infection and road injury).
... There are also methodological aspects which have to be taken into account. Despite some disadvantages randomized controlled trials (RCT) still are regarded as the "gold standard" for a clinical research (11,12). Treatment guidelines are usually based upon the results of RCTs or on systematic reviews/metaanalyses which in turn rest on the results acquired by RCTs and results of methodologically weak RCTs may alter their conclusions erroneously (13). ...
Object: Intracranial hemorrhage (ICH) is the second most common cause of stroke but still there is little consolidated knowledge about the optimal treatment strategies (e.g., the benefit of surgical evacuation). We evaluated the current randomized controlled trials (RCTs) on primary ICH (01.2013–03.2017) according to their fulfillment of the CONSORT statement's criteria (published in 2010) –as a marker of transparency and quality of study planning and realization. Methods: A Pubmed and a Cochrane database (including clinicaltrials.gov) search was carried out (01.2014–3.2017, respectively 01.2013–12.2013). Abstracts were screened for inclusion. Eligible full text manuscripts were assessed for the implementation of the CONSORT criteria. Citation frequencies and impact factors of the journals were related to ratio of CONSORT criteria fulfillment. Further, the risk of bias according to the Risk of bias tool 2 (RoB 2) was assessed. Results: Overall 3097 abstracts were screened for inclusion; 39 studies were suitable for final analysis. A mean fulfillment ratio of 51% (±28%) was found. A high correlation between impact factor and adherence to CONSORT criteria was shown (r = 0.7664; p < 0.0001). Citation frequency per year was related to ratio of CONSORT item fulfillment (r = 0.6747; p < 0.0001) and to the impact factor of the publishing journal (r = 0.7310; p < 0.0001). Of note, the items 10 (randomization: implementation) and 21 (generalizability) showed particularly high rates of non-fulfillment (87 and 85%). The majority of studies (95%) complied with item 2b (specific objectives or hypotheses), but strikingly objectives were mostly described vaguely. Other essential criteria such as sample size determination, definition of outcome parameters, and participant flow were only fulfilled weakly (51, 54, and 39%). Conclusions: Over 20 years after its inception there is still weak adherence to the CONSORT statement. As a consequence, conclusions are hampered by inadequate planning and/or reporting. Particularly with respect to pathologies as ICH lacking clear, evidence-based guidelines adherence to the CONSORT statement might improve research quality in order to define valuable treatment strategies.
... • Assess the generalizability (external validity) of the findings, e.g., determine whether descriptive normative information has the same effect for households in different geographic regions, climate zones and socio-cultural environments, for customers of other energy utilities, and/or at different points in time. Repeat the normative messaging intervention in other settings and with entirely different samples of residential energy consumers testing program efficacy and effectiveness, particularly in, but not limited to, the medical and healthcare domains [13,14,[37][38][39]. As Solomon and colleagues [12; p. 6] described it: ...
... According to de Craen et al. (1999) the first medical uses of the word 'placebo' dates from the late XVIII Century. But it is not until the second half of XX century that placebo started to be systematically used in control groups, as part of the randomized controlled trials (Meldrum 2000;Dehue 1997). In this period, placebo started to be considered as a useful tool to discriminate between the effects caused by the specific factors of the treatment, and those caused by confounding non-specific factors, such as the symbolic and social 'noises' attached to the relationship between the patient and practitioner. ...
The perspectives of medical anthropology on symbolic cure are crucial for understanding placebo mechanisms on the medical agenda. However, while classic biomedical conceptions of the placebo discredited cultural factors as legitimate therapeutic tools, the anthropological critical approach confronted this perspective in the opposite way, rejecting the role of neurobiological factors, and using culture as a self-contained phenomenon. This manuscript is a review of the symbolic healing, stressing the importance of an integrated and interdisciplinary study of the placebo response, and the need to go beyond both biological and cultural reductionisms. Various perspectives from medical anthropology will be described, ranging from classical to multilevel perspectives that enable consideration of the placebo in its neurobiological, psychological and cultural dimensions.
... In clinical trials, the randomized controlled trial (RCT) is recognized as important to establish validity of causal associations between the intervention and studied subjects. [27][28][29] RCTs are usually performed by randomly allocating study subjects into different treatment groups, 30 in which each subject is enrolled into a group with an equal probability. The advantage of using randomization is the possibility of relaxing the underlying assumption that the majority of subject characteristics are not biased between groups under study and provide a basis for inference. ...
Omics technologies are ubiquitous in biomedical research. However, improper sample selection is an often-overlooked complication with large omics studies, resulting in confounding effects that can disrupt the internal validity of a study and lead to false conclusions. Here, we present a method called BalanceIT, which uses a genetic algorithm to identify an optimal set of samples with balanced clinical factors for large-scale omics experiments. We apply our approach to two large RNA-Seq studies in autism (1) to find a post-hoc balanced sample set among an imbalanced study, and (2) to design an optimal study that allows for efficient batch correction. Our approach leads to near-perfect estimates of differential gene expression, superior performance of pathway-level enrichment analysis, and consistent network dysregulation patterns of autism symptom severity. These results provide empirical support for the importance of balanced experimental design, and BalanceIT will be invaluable for large-scale study design and batch effect correction.
... Public health interventions, in contrast, have features that often necessitate using evidence from other sources [13,21,22,32,34] . While there are known historical examples of trials of interventions to improve population health [30] , trials can be challenging in the public health context due to practical and ethical reasons. For example, PHIs generally have outcomes that are difficult to quantify in the shortterm and that spill over to sectors outside of healthcare (i.e. ...
Objectives: Health technology assessments (HTAs) have been suggested as a strategy to bridge the evidence-to-policy gap in public health. It is unclear to what extent HTAs have been prepared to assist decisions to implement public health interventions (PHIs). We aimed to describe the experience of HTA agencies by mapping, classifying, and analyzing the evidence content of HTAs of PHIs.
Methods: We systematically searched databases of 35 HTA agencies from 18 countries for evaluations of PHIs between 2008-2018. Interventions were classified using the International Classification of Health Interventions and the evidence content analysed with the INAHTA Product-Type-mark checklist.
Results: Only 1010 (9%) of HTAs were on PHIs. 500 (50%) publications targeted Body Systems and Functions, 302 (30%) Health-related Behaviours, 137 (14%) the Environment and 44 (4%) Activities and Participation Domains. Out of 734 publications perused, few met the criteria of full-HTAs (71;10%) or mini-HTAs (110;15%). Most were rapid reviews (420;57%). 72% of all reports came from only 6 countries.
Conclusion: HTAs on PHIs were uncommon relative to clinical interventions. HTAs on population-based PHIs were less comprehensive in quality and rigor of the evidence. Countries with more resources and mature HTA-systems had done the most evaluations. Exploring the experiences of forerunners could help overcome barriers to evaluations of PHIs and exploit the full potential of HTAs to promote evidence-based public health.
... Randomised experiments first appeared in psychology, where they were introduced by Charles Sanders Peirce in 1885 [152], and the first published RCT appeared in 1948 [130]. A brief history of the RCTs can be found in [131]. ...
Multimorbidity, i.e., the presence of multiple diseases within one person, is a significant health-care problem for western societies: diagnosis, prognosis and treatment in the presence of of multiple diseases can be complex due to the various interactions between diseases. To better understand the co-occurrence of diseases, we propose Bayesian network structure learning methods for deriving the interactions between risk factors. In particular, we propose novel measures for structural relationships in the co-occurrence of diseases and identify the critical factors in this interaction. We illustrate these measures in the oncological area for better understanding co-occurrences of malignant tumours.
... clinical trials, cohort studies, observational studies, case studies, and more (Concato et al., 2000). Of these study types, randomized controlled trials (RCTs) offer the highest quality of evidence (Meldrum, 2000). ...
To assess the effectiveness of any medical intervention, researchers must conduct a time-intensive and highly manual literature review. NLP systems can help to automate or assist in parts of this expensive process. In support of this goal, we release MS^2 (Multi-Document Summarization of Medical Studies), a dataset of over 470k documents and 20k summaries derived from the scientific literature. This dataset facilitates the development of systems that can assess and aggregate contradictory evidence across multiple studies, and is the first large-scale, publicly available multi-document summarization dataset in the biomedical domain. We experiment with a summarization system based on BART, with promising early results. We formulate our summarization inputs and targets in both free text and structured forms and modify a recently proposed metric to assess the quality of our system's generated summaries. Data and models are available at https://github.com/allenai/ms2
... 67 Moreover, these experiments at Birmingham took place fifteen to twenty years before the randomized control trial had been formally and robustly outlined in the literature, pointing to how and why such problematic patterns came into being. 68 These metabolic trials, then, fall into the period during which historian Martin Edwards has argued that the 'use of comparison controls increased'. 69 The results from Birmingham's initial experiments on patients diverged from the literature because, they reasoned, their rigorous method was so precise. ...
This article will reveal how local scientific determination and ambition, in the face of rejection by funders, navigated a path to success and to influence in national policy and international medicine. It will demonstrate that Birmingham, England's ‘second city’, was the key centre for cutting-edge biological psychiatry in Britain in the 1920s and 1930s. The ambitions of Frederick Mott – doyen of biochemistry, neuropathology and neuropsychiatry, until now celebrated as a London figure – to revolutionize psychiatric treatment through science, chimed with those of the City and University of Birmingham's Joint Board of Research for Mental Diseases. Under Mott's direction, shaped by place and inter-professional working, the board's collaborators included psychiatrist Thomas Chivers Graves and world-renowned physiologist J.S. Haldane. However, starved of external money and therefore fresh ideas, as well as oversight, the ‘groupthink’ that emerged created the classic UK focal sepsis theory which, it was widely believed, would yield a cure for mental illness – a cure that never materialized. By tracing the venture's growth, accomplishments and contemporary potential for biochemical, bacterial and therapeutic discoveries – as well as its links with scientist and key government adviser Solly Zuckerman – this article illustrates how ‘failure’ and its ahistorical assessment fundamentally obscure past importance, neglect the early promise offered by later unsuccessful science, and can even hide questionable research.
... In continued attempts to develop effective interventions to improve and promote health and well-being and eliminate health inequities, randomized controlled trials (RCTs) are an important design for conducting rigorous tests of interventions with high internal validity. Despite significant questions and concerns, RCTs remain a critical tool and the "gold standard" for measuring intervention effectiveness (Meldrum, 2000). There is growing recognition, however, that certain limitations should be addressed in any study that employs an RCT design, including examining external validity (Rothwell, 2005), incorporating methods for explicating mechanisms of change and understanding participants' intervention experiences (Hawe, Shiell, & Riley, 2004), and carefully exploring the feasibility and acceptability of an experimental design (Rychetnik, Frommer, Hawe, & Shiell, 2002). ...
Randomized controlled trials (RCTs) are a long-standing and important design for conducting rigorous tests of the effectiveness of health interventions. However, many questions have been raised about the external validity of RCTs, their utility in explicating mechanisms of intervention and participants’ intervention experiences, and their feasibility and acceptability. In the current mixed-methods study, academic and community partners developed and implemented an RCT to test the effectiveness of a collaboratively developed community-based advocacy, learning, and social support intervention. The goals of the intervention were to address social determinants of health and build trust and connections with other mental health services in order to reduce mental health disparities among Afghan, Great Lakes Region African, and Iraqi refugee adults and to engage and retain refugees in trauma-focused treatment, if needed. Two cohorts completed the intervention between 2013 and 2015. Ninety-three adult refugees were randomly assigned to intervention or control group and completed four research interviews (pre-, mid-, and postintervention, and follow-up). Several challenges to conducting a community-based RCT emerged, including issues related to interviewer intervention to assist participants in the control group, diffusion of intervention resources throughout the small refugee communities, and staff and community concerns about the RCT design and what evidence is meaningful to demonstrate intervention effectiveness. These findings highlight important epistemological, methodological, and ethical challenges that should be considered when conducting community-based RCTs and interpreting results from them. In addition, several innovations were developed to address these challenges, which may be useful for other community–academic partnerships engaged in RCTs.
... In the context of confirmatory clinical trials, the most common design is the randomized controlled clinical trial, where the measure of efficacy is the magnitude of benefit of the study treatment compared with controls. 168 In the engineering arena, a measurement instrument, such as a weighing scale, also produces estimates of some attribute of that which is being measured. Accurate and reliable output from a measurement instrument requires that each component of the instrument be calibrated. ...
The purpose of this article is to provide readers with a basis for understanding the emerging science of clinical trials and to provide a set of practical, evidence-based suggestions for designing and executing confirmatory clinical trials in a manner that minimizes measurement error. The most important step in creating a mindset of quality clinical research is to abandon the antiquated concept that clinical trials are a method for capturing data from clinical practice and shifting to a concept of the clinical trial as a measurement system, consisting of an interconnected set of processes, each of which must be in calibration for the trial to generate an accurate and reliable estimate of the efficacy (and safety) of a given treatment. The status quo of inaccurate, unreliable, and protracted clinical trials is unacceptable and unsustainable. This article gathers aspects of study design and conduct under a single broad umbrella of techniques available to improve the accuracy and reliability of confirmatory clinical trials across traditional domain boundaries.
... Although 2 meta-analyses focusing on CA and TSA have been conducted previously [6,12], ours is the first meta-analysis to include only RCTs-the 'gold standard' for clinical trials [48]. In the aforementioned meta-analyses, most of the involved studies had a retrospective design. ...
OBJECTIVES
There is an urgent need to understand the difference in the influence of thoracoscopic surgical ablation (TSA) and catheter ablation (CA) on clinical outcomes in patients with atrial fibrillation (AF). This meta-analysis of randomized controlled trials aimed to examine the efficacy and safety of TSA versus CA in patients with AF.
METHODS
Databases including EMBASE, Clinical Trials, PubMed and Cochrane Central Registered Control System were screened for the retrieval of articles. A direct meta-analysis of TSA versus CA was conducted. The I2 test analysis was performed to evaluate heterogeneity. The Begg–Mazumdar test and the Harbord–Egger test were used to detect publication bias. The primary efficacy outcome was freedom from atrial tachyarrhythmia, while the primary safety outcome was severe adverse event (SAE) occurrence.
RESULTS
Of the 860 identified articles, 6, comprising 466 participants, were finally included. The rate of freedom from AT was higher in the TSA group (75%) than in the CA group (57.1%) (odds ratio 0.41; 95% confidence interval 0.2–0.85; P = 0.02; I2 = 57%). A larger number of SAEs were observed in the TSA group than in the CA group (odds ratio 0.16; 95% confidence interval 0.006–0.46; P = 0.0006; I2 = 44%). The result of the subgroup analysis of 3 studies that enrolled AF patients without a history of ablation showed that the incidence of AT was comparable in both arms. The ablation procedure and hospitalization durations were longer in the TSA arm.
CONCLUSIONS
In our study, TSA was associated with better efficacy but a higher rate of SAEs compared to CA. In addition, TSA did not show better efficacy results as the first invasive procedure in the sub-analysis of patients with paroxysmal AF or early persistent AF. Therefore, doctors should recommend either TSA or CA to patients with AF after due consideration of the aforementioned findings.
... Although the origin of the clinical trial design dates back over 200 years to British naval surgeon James Lind's examination of causes of scurvy (Lind 1772, Meldrum 2000, the use of the RCT as the preferred evaluation design did not occur until the mid-twentieth century, starting first in the field of medicine (Med. Res. ...
In this article, we review the field of early childhood prevention and intervention science, describe noteworthy achievements over the past half-century by researchers in this area, and comment on current issues in need of ongoing attention. Although there have been many successes and noteworthy achievements in the field, in recent decades there has been little progress toward population-level impacts of early intervention. As such, novel empirical methods and revised standards of evidence are needed to complement (rather than replace) existing best practices for the development, implementation, evaluation, and scaling of effective programs.
... The contemporary RCT employed in medicine, is a slightly more refined version of forebearer factorial experimental designs, employed in education, psychology, and agriculture. Factorial designs were created by Sir Ronald Fisher [6] decades before the first published study that we today would label a randomized clinical trial, which was a test of streptomycin in treating tuberculosis, published in 1948 [7]. Fisher designed the experimental structure that evolved into the RCT for the purpose of studying crop yields on those famous plots of land at the Rothamsted Experimental Station in Hertfordshire, England. ...
During the recent era of evidence-based medicine, the randomized controlled trial (RCT) has been regarded as the most authoritative method of evaluating interventions. The methodology is utilized not only in medicine, but in other fields such as economics, education, and agriculture. In psychiatry and clinical psychology, RCTs have been utilized extensively in conjunction with the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM) [1]. This RCT/DSM combination has produced somewhat limited progress, both in identifying efficacious treatments and in facilitating progress in better understanding the scientific foundations of clinical intervention in these fields. This unhappy circumstance results not from limitations of the RCT as a tool of inductive logic, but rather its use with data that are neither theoretically grounded nor psychometrically sound, under background conditions in which publication bias and economic interest converge to distort the rational, impartial use of the RCT. Until the biases due to human interests are reduced and the fields of psychiatry and clinical psychology are more scientifically advanced, the RCT will be of limited use.
... Tusenvis av barn viste seg å vaere rammet. Talidomidskandalen førte til at dokumentasjonskravene for nye legemidler ble kraftig innskjerpet over hele verden (11). ...
p>Teorien om balansen mellom de fire kroppsvæskene – humoralpatologien – dominerte sykdomsforståelse og dermed også medisinsk behandling i 2000 år. Brekkmidler, årelating og avføringsmidler var hyppig brukte virkemidler for å rette opp i ”ubalanse” mellom kroppsvæskene, som var regnet som årsak til sykdom.
Det var ikke før på 1700-tallet at faktisk empirisk kunnskap ble etterspurt som begrunnelse for valg av behandlingsmetoder. Det å telle opp hvordan det gikk med pasienter som fikk en behandling, og sammenlikne med pasienter som ikke fikk behandlingen, var en ny måte å presentere behandlingseffekter på. Fra 1800-tallet av er det mange eksempler på at behandlingsmetoder ble prøvet ut ved å la annenhver pasient motta behandlingen.
Streptomycinstudien til UK Medical Research Council (1946) regnes for å være det første randomiserte kontrollerte forsøket innen medisinsk forskning, og for å ha satt standarden for hvordan kliniske utprøvninger bør utføres.
I boka ”Effectiveness and Efficiency. Random Reflections on Health Services” (1972) kritiserte Archie Cochrane mangelen på dokumentasjon for mange av tiltakene som utføres i helsetjenesten. Han ønsket seg langt flere randomiserte studier. Dessuten tok han til orde for at alle randomiserte studier burde samles, og at resultatene burde oppsummeres jevnlig. Iain Chalmers tok utfordringen og påbegynte et omfattende arbeid med å utarbeide en database over randomiserte kontrollerte forsøk. Med utgangspunkt i denne databasen ble det så utarbeidet systematiske oversikter over gjeldende kunnskap om effekt av tiltak i helsetjenesten. Dette ble starten på Cochrane-samarbeidet.
Fretheim A. Medical knowledge then and now: From theory to systematic reviews. Nor J Epidemiol 2013; 23 (2): 113-118.
ENGLISH SUMMARY
The humoral medicine-theory dominated the understanding of diseases and thus also medical treatments over 2,000 years. Purgatives, bloodletting and laxatives were frequently used to correct ”imbalances” between body fluids, which were seen as the cause of disease.
It was not until the 18th century that actual empirical knowledge was seen as important as a basis for making decisions about choice of treatment. At this time, the idea of counting the outcomes among patients receiving a treatment and compare with patients who did not, was a new approach for presenting treatment effects. As of the 19th century there are many examples of treatments being tested by the use of alternation, i.e. allocating every other patient to the treatment under evaluation.
The UK Medical Research Council’s streptomycin-trial (1946) is regarded as the first randomised controlled trial in medicine, and for having set the standard for clinical trials.
In his book, ”Effectiveness and Efficiency. Random Reflections on Health Services” (1972), Archie Cochrane criticised the lack of evidence for many of the interventions being performed in the health services. He called for far more randomised trials. He also proposed that findings from randomised trials should be collated, and that the results should be summarised on a regular basis. Iain Chalmers took the challenge and engaged in the huge task of developing a database of randomised controlled trials. With the database as a starting point, several systematic reviews of current evidence on the effects of interventions in the health services were produced. This was the start of the Cochrane Collaboration.</p
... In this case, especially ideals of evidence-based medicine 13,14 and randomized controlled trials as gold standard are crucial albeit debated. [15][16][17][18] Although negotiations on credibility take place in a number of contexts, publications in well-reputed peer review journals have been identified as crucial. The establishment of specialized journals is also considered as decisive, since journals and their editorial boards possess the capacity to control access to scientific communication (for example by determining relevant topics or which research designs are to be accepted). ...
Objectives
The aim of this article is to analyze the development of integrative oncology from a bibliometric point of view. The publication and citation patterns of publications are analyzed and their contents mapped.
Design
This study is based on bibliometric methods. The data sets consist of 7 025 respectively 4 990 publications over the time period 1966-2016, shown in PubMed and Web of Science.
Results
The expansion of the numbers of these publications took place in the late 1990s/early 2000s. Research is dominated by authors located in the USA, China and Germany who are working at well-established research universities and university hospitals. The clinical share of publications is relatively small, and few studies are classified according to clinical phase. Content analysis revealed that much of the clinical research is based on surveys, and that content reflects the intersection of complementary therapies and cancer research. The latter aspect is less obvious in pre-clinical research. The most frequent journals in the material show a focus on complementary and alternative therapies or on integrative oncology, although journals focused on oncology or general/internal medicine were well-represented in the material as a whole. The most-cited publications were review articles and surveys.
Conclusions
Integrative oncology has been established as a small, but distinct, research domain. There are several signs of specialization in integrative oncology, but also in its integration into general medical and oncological research.
... Currently NP-led cardiovascular (CV) care and the associated outcomes of care have not been broadly evaluated. Randomized controlled trials (RCT) are the gold standard to evaluate treatment efficacy (Meldrum, 2000). Therefore, the purpose of this study was to conduct a systematic review (SR) and meta-analysis of RCTs assessing NP-led CV care and associated outcomes of care. ...
Aim:
To assess randomized controlled trials evaluating the impact of nurse practitioner-led cardiovascular care.
Background:
Systematic review of nurse practitioner led-care in patients with cardiovascular disease has not been completed.
Design:
Systematic review and meta-analysis.
Data sources:
The Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL, Web of Science, Scopus, & ProQuest were systematically searched for studies published January 2007- June 2017.
Review methods:
Cochrane methodology was used for risk of bias, data extraction and meta-analysis. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation approach.
Results:
Out of 605 articles, five articles met inclusion criteria. There was no statistical difference between nurse practitioner-led care and usual care for 30-day readmissions, health related quality of life and length of stay. A 12% reduction in Framingham risk score was identified.
Conclusion:
There are few randomized control trials assessing nurse practitioner-led cardiovascular care.
Impact:
Low to moderate quality evidence was identified with no statistically significant associated outcomes of care. Nurse practitioner roles need to be supported to conduct and publish high quality research.
... when Daniel of Judah compared the health effects of vegetarian diet with a Babylonian diet over a 10day period (Jadad, 1998, Stolberg, Norman andTrop, 2004). More than 2,000 years later, after experimental philosophy and the idea of intentional comparison became popular after the scientific revolution of the 1400's, James Jurin compared the mortality rates of naturally occurring smallpox with that of cases occurring as a result of inoculation (Meldrum, 2000). Around the same time in the Chinese Qing Dynasty, a branch of scholarship known as Kao Zheng ushered a new epistemology valuing empirical measurement rather than theoretical interpretation of ancient Confucian texts (Boruch and Rui, 2009). ...
This paper covers the topic of randomized controlled trials in social, educational, criminological, health, and other human service sectors. It is studded with illustrations from developed and developing countries. We address the basic ideas that underlie trials in different ways, and cover contemporary definitions and vernacular, some history, and idea of cumulating evidence from such trials including recent work on replication and meta-analyses. Standards for evidence and reporting are considered. We attend to statistical matters and also recognize important non-statistical matters that must be taken into account in designing and executing such trials. Cluster randomized, place randomized, and other designs for such trials are covered on account of their increasing importance.
Randomized stepped-wedge (R-SW) designs are increasingly used to evaluate interventions targeting continuous longitudinal outcomes measured at T-fixed time points. Typically, all units start out untreated, and randomly chosen units switch to intervention at sequential time points until all receive intervention. As randomization is not always feasible, non-randomized stepped-wedge (NR-SW) designs (units switching to intervention are not randomly chosen) have attracted researchers. We develop an orthogonlized generalized least squares framework for both R-SW and NR-SW designs. The variance of the intervention effect estimate depends on the number of steps (S), length of step sizes (ts), and number of units (ns) switched at each step (s=1,…, S). If all other design parameters are equal, this variance is higher for the NR-SW than for the equivalent R-SW design (particularly if the intercepts of non-randomly stepped switching strata are analyzed as fixed effects). We focus on balanced stepped-wedge (BR-SW, BNR-SW) designs (where ts and ns remain constant across s) to obtain insights into optimality for variance of the estimated intervention effect. As previously observed for the BR-SW, the optimal choice for number of time points at each step is also [Formula] for the BNR-SW. In our examples, when compared to BR-SW designs, equivalent BNR-SW designs even with intercepts of non-randomly stepped switching strata analyzed using fixed effects sacrifice little efficiency given an intra-unit repeated measure correlation [Formula]. Compared to traditional difference-in-differences designs, optimal BNR-SW designs are more efficient with the ratio of variances of these designs converging to 0.75 when T > 10. We illustrate these findings using longitudinal outcomes in long-term care facilities.
http://deepblue.lib.umich.edu/bitstream/2027.42/107788/1/antuck.pdf
Janet G Bauer,1 Sue S Spackman,2 Robert Fritz,2 Amanjyot K Bains,3 Jeanette Jetton-Rangel3 1Advanced Education Services, 2Division of General Dentistry, 3Center of Dental Research, Loma Linda University School of Dentistry, Loma Linda, CA, USA Introduction: Best estimates of intervention outcomes are used when uncertainties in decision making are evidenced. Best estimates are often, out of necessity, from a context of less than quality evidence or needing more evidence to provide accuracy. Purpose: The purpose of this article is to understand the best estimate behavior, so that clinicians and patients may have confidence in its quantification and validation. Methods: To discover best estimates and quantify uncertainty, critical appraisals of the literature, gray literature and its resources, or both are accomplished. Best estimates of pairwise comparisons are calculated using meta-analytic methods; multiple comparisons use network meta-analysis. Manufacturers provide margins of performance of proprietary material(s). Lower margin performance thresholds or requirements (functional failure) of materials are determined by a distribution of tests to quantify performance or clinical competency. The same is done for the high margin performance thresholds (estimated true value of success) and clinician-derived critical values (material failure to function clinically). This quantification of margins and uncertainties assists clinicians in determining if reported best estimates are progressing toward true value as new knowledge is reported. Analysis: The best estimate of outcomes focuses on evidence-centered care. In stochastic environments, we are not able to observe all events in all situations to know without uncertainty the best estimates of predictable outcomes. Point-in-time analyses of best estimates using quantification of margins and uncertainties do this. Conclusion: While study design and methodology are variables known to validate the quality of evidence from which best estimates are acquired, missing are tolerance margins, or upper and lower performance requirements and clinician critical values, within which best estimates behave and are validated. Understanding the best estimate behavior toward true value may provide clinicians and patients confidence in decision making under uncertainty. Keywords: metric, outcomes, quantification of margins and uncertainties, true value, performance margins
We assemble studies within a set that we label randomized control trials (RCTs) in the US legal profession. These studies are field experiments conducted for the purpose of obtaining knowledge in which randomization replaces a decision that would otherwise have been made by a member of the US legal profession. We use our assembly of approximately 50 studies to begin addressing the question of why the US legal profession, in contrast to the US medical profession, has resisted the use of the RCT as a knowledge-generating device.
This article is concerned with the widely-established but pedagogically-neglected cognitive truism that anyone who sees, learns visually. Multimedia Learning (MML) scholarship, derived from the Cognitive Sciences, identifies a common cognitive architecture known as 'dual processing' shared by all sighted people. The literature predicts that people learn better from images and text than text alone, or predominantly. Subsequent peer-reviewed research establishes the veracity of this claim in a variety of institutions and disciplines. This requires a new conversation in HE about a generalizable multimedia pedagogy, a structure though which to establish principles and practice, and a mechanism to ascertain their effectiveness. It is all the more pertinent, since we may readily capitalize on the most visual era of human history to enable a transformed pedagogy. Yet we have failed largely to take proper stock of how this 'pictorial turn' in human evolution might support the generations we teach, for whom it is already a norm. The article discusses MML scholarship and predictions and how this can interject a potentially universal innovation into HE teaching and learning. It then discusses principles by which to reify such an innovation. Finally, it advances an innovative and shareable digital research tool to test such reification and discusses initial longitudinal data from a Randomized Control Trial. It concludes by identifying a further research agenda to compensate for present shortcomings in MML theory and data development.
A vile new mantra is on the lips of every public health official and politician in the global campaign to force universal masking on the general public: “there is a growing body of evidence”.
This propagandistic phrase is a vector designed to achieve five main goals:
- Give the false impression that a balance of evidence now proves that masks reduce the transmission of COVID-19
- Falsely assimilate commentary made in scientific venues with “evidence”
- Hide the fact that a decade’s worth of policy-grade evidence proves the opposite: that masks are ineffective with viral respiratory diseases
- Hide the fact that there is now direct observational proof that cloth masks do not prevent exhalation of clouds of suspended aerosol particles; above, below and through the masks
- Deter attention away from the considerable known harms and risks due to face masks, applied to entire populations
The said harms and risks include that a cloth mask becomes a culture medium for a large variety of bacterial pathogens, and a collector of viral pathogens; given the hot and humid environment and the constant source, where home fabrics are hydrophilic whereas medical masks are hydrophobic.
In short, I argue: op-eds are not “evidence”, irrelevance does not help, and more bias does not remove bias. Their mantra of “a growing body of evidence” is a self-serving contrivance that impedes good science and threatens public safety.
I prove that there is no policy-grade evidence to support forced masking on the general population, and that all the latest-decade’s policy-grade evidence points to the opposite: NOT recommending forced masking of the general population. Therefore, the politicians and health authorities are acting without legitimacy and recklessly.
The number of biomedical image analysis challenges organized per year is steadily increasing. These international competitions have the purpose of benchmarking algorithms on common data sets, typically to identify the best method for a given problem. Recent research, however, revealed that common practice related to challenge reporting does not allow for adequate interpretation and reproducibility of results. To address the discrepancy between the impact of challenges and the quality (control), the Biomedical Image Analysis ChallengeS (BIAS) initiative developed a set of recommendations for the reporting of challenges. The BIAS statement aims to improve the transparency of the reporting of a biomedical image analysis challenge regardless of field of application, image modality or task category assessed. This article describes how the BIAS statement was developed and presents a checklist which authors of biomedical image analysis challenges are encouraged to include in their submission when giving a paper on a challenge into review. The purpose of the checklist is to standardize and facilitate the review process and raise interpretability and reproducibility of challenge results by making relevant information explicit.
In recent years, with the rapid increase in the volume and accessibility of Real-World-Data (RWD) and Real-World-Evidence (RWE), we have seen the unprecedented opportunities for their use in drug clinical development and life-cycle management. RWD and RWE have demonstrated the significant potential to improve the design, planning, and execution of clinical development. Furthermore, they can feature in the designs as either a substitute or compliment to traditional clinical trials. However, to utilize RWD and RWE appropriately and wisely, it is critical to apply rigorous statistical methodologies that enable the robustness of results to be characterized and ascertained. Several statistical methodologies including exact matching, propensity score methods, matching-adjusted indirect comparisons and meta-analysis have been proposed for analyzing RWD. Among them, propensity score method is one of the most commonly used methods for non-randomized trials with indirect comparison. Although massive methodologies and examples have been published and discussed since propensity score methods were introduced, systematic review and discussion of how to rigorously use propensity score methods in the practical clinical development is still deficient. This paper introduces commonly used and emerging propensity score methods with detailed discussions of their pros and cons. Three different case studies are presented to illustrate the practical considerations of utilizing propensity score methods in the study design and evaluation utilizing real-world and historical data. Additional considerations including selection of patient populations, baseline covariates, propensity score methods, endpoints, sensitivity analysis and practical implementation flow in clinical development will be discussed.
Alleged "COVID-19 Pandemic" mandated government enforced lockdowns of citizens, leading to massive but ignored K -12 suicide deaths of our children is connectable to Dr. Anthony Fauci.
Introduction:
An expected future increase in older adults will demand changes in health care delivery, making development, implementation and evaluation of new health care models essential. The rationale for political decision-making concerning the implementation and application of interventions in health care should include cost estimations, specifically those involving clinical interventions. To provide such data knowledge of time spent on the intervention is imperative. Time and motion methodology is suitable to quantify health care personnel's time distribution.
Aim:
To investigate the time distribution for pharmacists conducting a randomized controlled trial (RCT) implementing a clinical intervention.
Materials and methods:
The setting was an RCT with a 5-step pharmacist-intervention in collaboration with the interdisciplinary team in a geriatric ward. Two pharmacists were involved in the trial during the observation period. Pharmacist activities, classified as RCT-tasks (intervention or administrative), non-RCT tasks and social/breaks, were recorded applying the Work Observation Method By Activity Timing methodology, enabling recording of predefined work tasks as well as interruptions and multitasking. One observer collected data over eight weeks.
Results:
In total, 109.1 hours were observed resulting in 110.2 hours total task time, including multitasking. RCT tasks comprised 85.4% of the total observed time, and nearly 60% of the RCT time was spent on intervention tasks. Medication reviews was the most time consuming task, accounting for 32% of the observed time. The clinical pharmacists spent 14% of the intervention time communicating verbally, mainly with patients and healthcare professionals.
Conclusion:
During the RCT, the clinical pharmacists spent about half their time performing the actual intervention. Consequently, costs for providing such a clinical pharmacist service should reflect actual time spent; otherwise, we may risk overestimating theoretical costs.
Background
Intervention effect on ongoing medical processes is estimated from clinical trials on units (i.e. persons or facilities) with fixed timing of repeated longitudinal measurements. All units start out untreated. A randomly chosen subset is switched to the intervention at the same time point. The pre-post switch change in the outcome between these units and unswitched controls is compared using Generalized Least Squares models. Power estimation for such studies is hindered by lack of available GLS based approaches and normative data.
Methods
We derive Generalized Least Squares variance of the intervention effect. For the commonly assumed compound symmetry correlation structure, this leads to simple power formulas with important optimality properties. To maximize power given a constrained number of total time points, we investigate on the optimal pre-post allocation with the local minimization of variance.
Results
In four examples from nursing home and HIV patients, the Toepltiz within-unit correlation of repeated measures differed from compound symmetry. We applied empirical Toeplitz based calculations for variance of the estimated intervention effect to these examples (each with up to seven longitudinal measures). Unlike what happened under compound symmetry, where power was often maximized with multiple observations being pre-intervention, for these examples, having one pre-intervention measure tended to maximize power. Attempts to approximate the Toeplitz variance structures with compound symmetry (to take advantage of the simpler formulas) resulted in overestimation of power for these examples.
Conclusions
While compound symmetry correlation among repeated within-unit measures leads to simple power estimation formulas, this structure often did not hold. There may be strong underestimation of variance of the intervention effect estimate from incorporating short-term within-unit correlation estimates as a common compound symmetry correlation to approximate an unknown Toeplitz correlation without adequately accounting for the correlation between repeated measures declining with time.
The polio vaccine field trials of 1954, sponsored by the National Foundation for Infantile Paralysis (March of Dimes), are among the largest and most publicised clinical trials ever undertaken. Across the United States, 623 972 schoolchildren were injected with vaccine or placebo, and more than a million others participated as “observed” controls. The results, announced in 1955, showed good statistical evidence that Jonas Salk’s killed virus preparation was 80-90% effective in preventing paralytic poliomyelitis.1
A review of the published literature on propoxyphene hydrochloride was undertaken to determine if the wide popularity of the drug is justified. Only double-blind studies were reviewed; 20 were identified in a bibliography of 243 articles. In the course of the review, deficiencies in the design, conduct, and reporting of the clinical studies were noted. The addiction liability of propoxyphene is low but several reports have demonstrated its abuse potential. The reviewed studies show that propoxyphene is not superior to codeine or aspirin in terms of analgesic effect. No definite statement as to relative incidence of side effects can be made. It appears that factors other than intrinsic therapeutic value are responsible for the commercial success of propoxyphene.
The fallibility of enthusiastic claims for new drugs makes it desirable to recognize those investigations which are likely to yield substantial data and to lead to interpretations that can be ascribed to pharmacodynamic effects rather than to wish, prejudice, coincidence, accident, or error. Some new drugs, despite statistical validations in reports of their efficacy and safety, do not survive the test of actual use or, even worse, have serious repercussions. The undesirable effects of such drugs employed therapeutically already have achieved alarming proportions, being observed in approximately 5% of 1,000 consecutive recent admissions to a major hospital in the city of New York.1 This situation may become even worse if the present rate of development of new drugs continues (about 550 new preparations each year or more than one every day2) and if the medical profession continues to be misled by poorly conducted or inadequate evaluations of new
In a double-blind crossover study of marketed drugs given by the oral route to relieve pain, aspirin (650 mg) was superior to all agents tested. Mefenamic acid (250 mg), pentazocine (50 mg), acetaminophen (650 mg), phenacetin (650 mg) and codeine (65 mg) also showed a significant advantage over a placebo. Propoxyphene (65 mg), ethoheptazine (75 mg) and promazine (25 mg) gave no significant evidence of therapeutic activity; and each of these agents was significantly inferior to aspirin in analgesic effect. Pentazocine (50 mg) produced sufficient gastrointestinal and Central-nervous-system side effects to make this agent of dubious value for ambulatory patients. All other drugs tested in this single dose study did not produce significantly greater side effects than a placebo.