Randomised controlled trials (RCTs) are often seen as the 'gold standard' of evaluative research. However, whilst randomisation will ensure comparable groups, trials are still vulnerable to a range of biases that can undermine their internal validity. In this paper we describe a number of common threats to the internal validity of RCTs and methods of countering them. We highlight a number of examples from randomised trials in education and health care where problems of execution and analysis (...) of the RCT has undermined their internal validity. However, awareness of these potential biases can lead to careful planning to avoid or reduce their occurrence. If good quality randomised trials are to inform policy and practice in education then rigorous trials need to be designed that are the least susceptible to threats to their validity. (shrink)

This paper argues for more randomised controlled trials in educational research. Educational researchers have largely abandoned the methodology they helped to pioneer. This gold-standard methodology should be more widely used as it is an appropriate and robust research technique. Without subjecting curriculum innovations to a RCT then potentially harmful educational initiatives could be visited upon the nation's children.

This article brings a historical perspective to explain the recent dissemination of randomized controlled trials (RCTs) as the new “gold standard” method to assess international development projects. Although the buzz around RCT evaluations dates from the 2000s, we show that what we are witnessing now is a second wave of RCTs, while a first wave began in the 1960s and ended by the early 1980s. Drawing on content analysis of 123 RCTs, participant observation, and secondary sources, we (...) compare the two waves in terms of the participants in the network of expertise required to carry out field experiments and the characteristics of the projects evaluated. The comparison demonstrates that researchers in the second wave were better positioned to navigate the political difficulties caused by randomization. We explain the differences in the expertise network and in the type of projects as the result of concurrent transformations in the fields of development aid and the economics profession. We draw on Andrew Abbott’s concept of “hinges,” as well as on Bourdieu’s concept of “homology” between fields, to argue that the similar positions and parallel struggles conducted by two groups of actors in the two fields served as the basis for a cross-field alliance, in which RCTs could function as a “hinge” linking together the two fields. (shrink)

This article brings a historical perspective to explain the recent dissemination of randomized controlled trials (RCTs) as the new “gold standard” method to assess international development projects. Although the buzz around RCT evaluations dates from the 2000s, we show that what we are witnessing now is a second wave of RCTs, while a first wave began in the 1960s and ended by the early 1980s. Drawing on content analysis of 123 RCTs, participant observation, and secondary sources, we (...) compare the two waves in terms of the participants in the network of expertise required to carry out field experiments and the characteristics of the projects evaluated. The comparison demonstrates that researchers in the second wave were better positioned to navigate the political difficulties caused by randomization. We explain the differences in the expertise network and in the type of projects as the result of concurrent transformations in the fields of development aid and the economics profession. We draw on Andrew Abbott’s concept of “hinges,” as well as on Bourdieu’s concept of “homology” between fields, to argue that the similar positions and parallel struggles conducted by two groups of actors in the two fields served as the basis for a cross-field alliance, in which RCTs could function as a “hinge” linking together the two fields. (shrink)

Objective: To assess whether continuous consent, a process in which information is given to research participants at different stages in a trial, and clinician training in that process were effective when used by clinicians while gaining consent to the Total Body Hypothermia (TOBY) trial. The TOBY trial is a randomised controlled trial (RCT) investigating the use of whole-body cooling for neonates with evidence of perinatal asphyxia. Obtaining valid informed consent for the TOBY trial is difficult, but is a good (...) test of the effectiveness of continuous consent. Methods: Semistructured interviews were conducted with 30 sets of parents who consented to the TOBY trial and with 10 clinicians who sought it by the continuous consent process. Analysis was focused on the validity of parental consent based on the consent components of competence, information, understanding and voluntariness. Results: No marked problems with consent validity at the point of signature were observed in 19 of 27 (70%) couples. Problems were found mainly to lie with the competence and understanding of the parents: mothers, particularly, had problems with competence in the early stages of consent. Problems in understanding were primarily to do with side effects. Problems in both competence and understanding were observed to reduce markedly, particularly for mothers, in the post-signature phase, when further discussion took place. Randomisation was generally understood but unpopular. Information was not always given by clinicians in stages during the short period available before parents gave consent. Most clinicians, however, were able to give follow-up information. Discussion: Consent validity was found to compare favourably with similar trials examined in the Euricon study. Conclusion: Adopting the elements of the continuous consent process and clinician training in RCTs should be considered by researchers, particularly when they have concerns about the quality of consent they are likely to obtain by using a conventional process. (shrink)

Randomised controlled trials (RCTs) sometimes recruit participants who are desperate to receive the experimental treatment. This paper defends the practice against three arguements that suggest it is unethical first, desperate volunteers are not in equipoise. Second clinicians, entering patients onto trials are disavowing their therapeutic obligation to deliver the best treatment; they are following trial protocols rather than delivering individualised care. Research is not treatment; its ethical justification is different. Consent is crucial. Third, desperate volunteers do not (...) give proper consent: effectively, they are coerced. This paper responds by advocating a notion of equipoise based on expert knowledge and widely shared values. Where such collective, expert equipoise exists there is a prima facie case for an RCT. Next the paper argues that trial entry does not involve clinicians disavowing their therapeutic obligation; individualised care based on insufficient evidence is not in patients best interest. Finally, it argues that where equipoise exists it is acceptable to limit access to experimental agents; desperate volunteers are not coerced because their desperation does not translate into a right to receive what they desire. (shrink)

The standardised randomised clinical trial (RCT) has been exceedingly popular in medical research, economics, and practical policy making. Recently, RCTs have faced criticism. First, it has been argued by John Worrall that we cannot be certain that our sample is not atypical with regard to possible confounding factors. I will argue that at least in the case of medical research, we know enough about the relevant causal mechanisms to be justified to ignore a number of factors we have good reason (...) not to expect to be disruptive. I will also argue against an argument provided by Nancy Cartwright and Eileen Munro that RCTs should not be taken to deductively infer probabilistic causal claims, but ampliatively. The paper will end on a discussion of evidence hierarchies and a defence of the stance of evidence-based medicine that RCTs are the best available method to assess a treatment’s efficacy. (shrink)

The aim of unpaid volunteer classroom assistants is to give extra support to children learning to read. The impact of using volunteers to improve children's acquisition of reading skills is unknown. To assess whether volunteers are effective in improving children's reading, we undertook a systematic review of all relevant randomised controlled trials (RCTs). An exhaustive search of all the main electronic databases was carried out (i.e. BEI, PsycInfo, ASSIA, PAIS, SSCI, ERIC, SPECTR, SIGLE). We identified eight experimental studies, (...) of which seven were RCTs. One of the RCTs was excluded because it did not meet the inclusion criteria. One RCT randomised intact classes and the other six studies randomised individual children and could therefore be included in a meta-analysis. All of the trials were fairly small, with the largest including 99 pupils. Four of the trials showed a positive outcome, while three showed a negative effect and the remaining study was equivocal. We pooled the four most homogeneous trials. The pooled data indicated an effect size of 0.19, which was not statistically significant ( p = 0.54, 95% confidence interval = -0.31 to 0.68). Overall, volunteering appeared to have a small effect on reading outcomes. However, the confidence intervals were wide, which could conceal a potentially large benefit or a harmful effect. Thus, more good quality RCTs are required in order to provide more conclusive evidence. (shrink)

This article focuses on maternal-fetal surgery (MFS) and on the concept of clinical equipoise that is a widely accepted requirement for conducting randomized controlled trials (RCT). There are at least three reasons why equipoise is unsuitable for MFS. First, the concept is based on a misconception about the nature of clinical research and the status of research subjects. Second, given that it is not clear who the research subject/s in MFS is/are, if clinical equipoise is to be (...) used as a criterion to test the ethical appropriateness of RCT, its meaning should be unambiguous. Third, because of the multidisciplinary character of MFS, it is not clear who should be in equipoise. As a result, we lack an adequate criterion for the ethical review of MFS protocols. In our account, which is based on Chervenak and McCullough's seminal work in the field of obstetric ethics, equipoise is abandoned. and RCT involving MFS can be ethically initiated when a multidisciplinary ethics review board (ERB), having an evidence-based assessment of the risks involved, is convinced that the value of answering the research hypothesis, for the sake of the health interests of future pregnant women carrying fetuses with certain congenital birth defects, justifies the actual risks research participants might suffer within a set limit of low/manageable. (shrink)

The transferability problem—whether the results of an experiment will transfer to a treatment population—affects not only Randomized Controlled Trials but any type of study. The problem for any given type of study can also, potentially, be addressed to some degree through many different types of study. The transferability problem for a given RCT can be investigated further through another RCT, but the variables to use in the further experiment must be discovered. This suggests we could do better (...) on the epistemological problem of transferability by promoting, in the repeated process of formulating public health guidelines, feedback loops of information from the implementation setting back to researchers who are defining new studies. (shrink)

The purpose of this study is to examine the importance that real patients attach to their right to withdraw from an on-going feasibility randomised trial (RCT) evaluating types and timings of breast reconstruction (two parallel trials) following mastectomy for breast cancer. Our results show that, while some respondents appreciated that exercising the right to withdraw would defeat the scientific objective of the trial, some patients with a surgical preference consented only given the knowledge they could withdraw if they were (...) not allocated to their preferred treatment. (shrink)

Various publications claim that medical AI systems perform as well, or better, than clinical experts. However, there have been very few controlled trials and the quality of existing studies has been called into question. There is growing concern that existing studies overestimate the clinical benefits of AI systems. This has led to calls for more, and higher-quality, randomized controlled trials of medical AI systems. While this a welcome development, AI RCTs raise novel methodological challenges that (...) have seen little discussion. We discuss some of the challenges arising in the context of AI RCTs and make some suggestions for how to meet them. (shrink)

Randomized controlled trials (RCTs) are a major success story, promising to improve science and policy. Despite some controversy, RCTs have spread toward Northern and Southern countries since the early 2000s. How so? Synthesizing previous research on this question, this article argues that favorable institutional conditions turned RCTs into “hinges” between the fields of science, politics, and business. Shifts toward behavioral economics, New Public Management, and evidence-based philanthropic giving led to a cross-fertilization among efforts in rich and poor (...) countries, involving states, international organizations, NGOs, researchers, and philanthropic foundations. This confluence of favorable institutional conditions and savvy social actors established a “global interstitial field” inside which support for RCTs has developed an unprecedented scope, influence, operational capacity, and professional payoff. However, the article further argues that the hinges holding together this global interstitial field are “squeaky” at best. Because actors inherit the illusio of their respective fields of origin—their central incentives and stakes—the interstitial field produces constant goal conflicts. Cooperation between academics and practitioners turns out to be plagued by tensions and contradictions. Based on this analysis, the article concludes that the global field of RCT support will probably differentiate into its constituent parts. As a result, RCTs may lose the special status they have gained among social science and policy evaluation methods, turning into one good technique among others. (shrink)

Social anxiety disorders (SAD) are among the most prevalent mental disorders (lifetime prevalence: 7–12%), with high impact on the life of an affected social system and its individual social system members. We developed a manualized disorder-specific integrative systemic and family therapy (ISFT) for SAD, and evaluated its feasibility in a pilot randomized controlled trial (RCT). The ISFT is inspired by Helm Stierlin’s concept of related individuation developed during the early 1980s, which has since continued to be refined. It (...) integrates solution-focused language, social network diagnostics, and genogram work, as well as resource- and problem orientation for both case conceptualization and therapy planning. Post-Milan symptom prescription to fluidize the presented symptoms is one of the core interventions in the ISFT. Theoretically, the IFST is grounded in radical constructivism and “Cybern-Ethics,” multi-directional partiality, and a both/and attitude toward a disorder-specific vs. non-disorder-specific therapy approach. SAD is understood from the viewpoint of social systems theory, especially in adaptation to a socio-psycho-biological explanatory model of social anxiety. In a prospective multicenter, assessor-blind pilot RCT, we included 38 clients with SAD (ICD F40.1; Liebowitz Social Anxiety Scale, LSAS-SR > 30): 18 patients participated in the ISFT, and 20 patients in Cognitive Behavioral Therapy (CBT; age:M = 36 years,SD = 14). Within-group, simple-effect intention-to-treat analyses showed significant reduction in social anxiety (LSAS-SR; ISFT:d = 1.67; CBT:d = 1.04), while intention-to-treat mixed-design ANOVA demonstrated the advantage of ISFT (d = 0.81). Per-protocol analyses supported these results. The remission rate based on blind diagnosticians’ ratings was good to satisfactory (Structured Clinical Interview, SCID; 78% in ST, 45% in CBT,p = 0.083); this has yet to be verified in a subsequent confirmatory RCT. The article will present the ISFT rationale and manual, including a special focus on multi-person settings, and the central findings from our pilot RCT. (shrink)

Clinicians are required to act in the best interest of neonates.However, it is not obvious that entry into a randomised controlled trial (RCT) is in a neonate’s best interest because such trials often involve additional onerous procedures (such as intramuscular injections) in return for which the neonate receives unproven treatment or a placebo.On the other hand, neonatology needs to develop its evidence base, and RCTs are central to this task. The solution posited here is based on two points. (...) First, “best interest” is not equivalent to “the best possible interest” only to “best interest within a certain realm”. The realm of deliberation when asking the title question is the neonate’s health. Deliberating in this realm may involve the exclusion from consideration of some factors that might be thought relevant (such as parental wealth). Furthermore, circumstances may dictate the need to deliberate on other factors that might be thought irrelevant (such as health care resources). Second, deciding on a neonate’s best interest does not involve “putting oneself in its shoes”. Rather, it involves asking in what it has an interest, or stake. These will include some things in which we all, as human beings, have a stake, such as medical progress. Putting these two points together, in the realm of health the answer to whether RCT entry is in a neonate’s best interest is usually very finely balanced. Where this is the case, it is reasonable to invoke a broader notion of best interest and include a broader range of elements in which the neonate has a stake, including medical progress. In this way RCT entry can, usually, be said to be in a neonate’s best interest. (Journal of Medical Ethics 2001;27:110–113) Keywords: Neonates; randomised controlled trials; best interest; ethics. (shrink)

Randomized controlled trials (RCTs) are widely taken as the gold standard for establishing causal conclusions. Ideally conducted they ensure that the treatment ‘causes’ the outcome—in the experiment. But where else? This is the venerable question of external validity. I point out that the question comes in two importantly different forms: Is the specific causal conclusion warranted by the experiment true in a target situation? What will be the result of implementing the treatment there? This paper explains how (...) the probabilistic theory of causality implies that RCTs can establish causal conclusions and thereby provides an account of what exactly that causal conclusion is. Clarifying the exact form of the conclusion shows just what is necessary for it to hold in a new setting and also how much more is needed to see what the actual outcome would be there were the treatment implemented. (shrink)

The application of evidence-based medicine helps clinicians avoid unnecessary procedures and decreases unnecessary harm for future patients while sparing economic burdens. Randomised controlled trials (RCTs) most accurately produce best research evidence. In arthroscopic surgery, however, many procedures have been extensively used without supportive evidence verified with RCTs. In this paper, we introduce two procedures (arthroscopic partial menisectomy for degenerative knees and arthroscopic subacromial decompression for subacromial pain syndrome), where over 30 years of procedure usage has continued prior to (...) garnering evidence for the inefficacy of the procedures. The situations are attributed to the fact that clinical trials in arthroscopic surgeries are challenging given the use of placebo controls. A placebo-control RCT can accurately answer research questions about efficacy and safety of surgical procedures; however, the majority of arthroscopic surgeries in practice have not been rigorously tested against placebo surgeries. This is because preparing surgical placebo controls, known as sham surgeries, are ethically controversial. Also considering that high-quality study results often do not change clinical practice due to insufficient knowledge translation, the benefits of such trials may be uncertain to society at large. Additionally, there are a lack of clear guidelines for conducting arthroscopic placebo surgeries in RCTs. We hope that this article helps drive discussion about appropriate use of placebo surgeries in RCTs to produce the best quality evidence in arthroscopic surgery. (shrink)

The primary purpose of this randomized controlled trial (RCT) was to evaluate the efficacy of an unguided, two-week internet-based training program to overcome procrastination, called ON.TOP. Because adherence is a typical problem among individuals who tend to procrastinate, especially with internet-based interventions, the secondary purpose of the present study was to investigate whether adding SMS support increases subjects’ frequency of engagement in training. In a three-armed RCT (N = 161), the effects of the intervention alone and intervention with (...) daily SMS-support were compared to a waiting list control condition in a sample of students. The primary outcome of interest was procrastination. The secondary outcome of interest was the extent of training behavior. Baseline (T0), immediate post-treatment (T1) and 8-week post-treatment (T2) assessments were conducted. Results indicated that procrastination decreased significantly only with intervention group with daily SMS support, relative to control. Moreover, incorporating SMS support also may enhance extent of training behavior. (shrink)

Madole & Harden argue that just as the results of randomized controlled trials (RCTs) represent gains in causal knowledge and are useful, despite their limitations, so too are the findings of human behavior genetics. We argue that this analogy is misleading. Unlike RCTs, the results of human behavior genetics research cannot suggest efficacious interventions, nor point toward future research.

BackgroundTrial registration helps minimize publication and reporting bias. In leading medical journals, 96% of published trials are registered. The aim of this study was to determine the proportion of randomized controlled trials published in key nursing journals that met criteria for timely registration.MethodsWe reviewed all RCTs published in three (two general, one mental health) nursing journals between August 2011 and September 2016. We classified the included trials as: 1. Not registered, 2. Registered but not reported (...) in manuscript, 3. Registered retrospectively, 4. Registered prospectively (before the recruitment of the first subject into the trial). 5. Timely registration (as 4 but the trial identification number is reported in abstract).ResultsWe identified 135 trials published in the three included journals. The majority (n = 78, 58%) were not registered. Thirty-three (24%) were retrospectively registered. Of the 24 (18%) trials that were prospectively registered, 11 (8%) met the criteria for timely registration.ConclusionsThere is an unacceptable difference in rates of trial registration between leading medical and nursing journals. Concerted effort is required by nurse researchers, reviewers and journal editors to ensure that all trials are registered in a timely way. (shrink)

Objective: This meta-analysis evaluated the efficacy of acupuncture in improving cognitive impairment of post-stroke patients.Design: Randomized controlled trials investigating the effects of acupuncture compared with no treatment or sham acupuncture on post-stroke cognitive impairment before December 2019 were identified from databases. The literature searching and data extracting were independently performed by two investigators. Study quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analyses were performed for the eligible RCTs with Revman 5.3 software.Results: Thirty-seven (...) RCTs were included in this meta-analysis. Merged Random-effects estimates of the gain of MMSE or MoCA were calculated for the comparison of acupuncture with no acupuncture or sham acupuncture. Following 2–8 weeks of intervention with acupuncture, pooled results demonstrated significant effects of acupuncture in improving PSCI assessed by MMSE or MoCA.Conclusion: The results suggest that acupuncture was effective in improving PSCI and supported the needs of more rigorous design with large-scale randomized clinical trials to determine its therapeutic benefits. (shrink)

In his recent book, Keith Morrison argues that RCTs have garnered a privileged place in educational research, driving out other valuable approaches. Morrison acknowledges RCTs or similar designs ca...

One important ethical issue in randomised controlled trials is randomisation. Relatively little is known about how participating individuals and communities understand and perceive central aspects of randomisation such as equality, fairness, transparency and accountability in community-based trials. The aim of this study was to understand and explore study communities’ perspectives of the randomisation process in a cluster RCT in rural Zambia studying the effectiveness of different support packages for adolescent girls on early childbearing. In this explorative study, (...) in-depth semi-structured interviews were carried out in 2018 with 14 individuals who took part in the randomisation process of the Research Initiative to Support the Empowerment of Girls project in 2016 and two traditional leaders. Two of the districts where the trial is implemented were purposively selected. Interviews were audio recorded and fully transcribed. Data were analysed by coding and describing emergent themes. The understanding of the randomisation process varied. Some respondents understood that randomisation was conducted for research purposes, but most of them did not. They had trouble distinguishing research and aid. Generally, respondents perceived the randomisation process as transparent and fair. However, people thought that there should not have been a “lottery” because they wanted all schools to receive equal or balanced benefits of the interventions. Randomisation was misunderstood by most respondents. Perceived procedural fairness was easier to realize than substantive fairness. Researchers working on Cluster Randomised Controlled Trials should consider carefully how to explain randomisation. (shrink)

We raise a problem of applicability of RCTs to validate nuclear diagnostic imaging tests. In spite of the wide application of PET and other similar techniques that use radiopharmaceuticals for diagnostic purposes, RCT-based evidence on their validity is sparse. We claim that this is due to a general conceptual problem that we call Prevalence of Treatment, which arises in connection with designing RCTs for testing any diagnostic procedure in the present context of medical research, and is particularly apparent in this (...) case. We also identify three practical reasons why RCTs do not qualify as the best option for PET validation, which have to do with specific characteristics of nuclear diagnostic imaging, and of radiopharmaceuticals. The paper is meant to contribute both to the philosophical discussion on the EBM hierarchy of evidence, and on the specific debate on radiopharmaceuticals in nuclear medicine. (shrink)

There are differences in caregivers’ literacy and health literacy levels that may affect their ability to consent to children participating in clinical research trials. This study aimed to explore the effectiveness, and caregivers’ understandings, of the process of informed consent that accompanied their child’s participation in a dental randomized control trial (RCT). Telephone interviews were conducted with a convenience sample of ten caregivers who each had a child participating in the RCT. Pre-tested closed and open-ended questions were used, (...) and the findings were produced from an inductive analysis of the latter and a descriptive analysis of the former. Participants had limited understanding of the purpose of the RCT and rated the readability of the consent form more highly than they rated their understanding of the research. All felt that informed consent was vital, but some caregivers had not read the consent documents. Some caregivers enrolled their child in the RCT because they trusted the researchers, and the majority wanted to improve dental care for children. The informed consent process was not always effective despite high readability of the informed consent documents. Researchers must consider the health literacy of the study group, and actively engaging with caregivers to achieve meaningful informed consent may be challenging. Future research could explore participants’ perspectives of informed consent in populations with low health literacy and assess whether an underlying expectation not to comprehend health-related information may be a barrier to informed consent. (shrink)

Background Pragmatic randomized controlled trials are designed to evaluate the effectiveness of interventions in real-world clinical conditions. However, these studies raise ethical issues for researchers and regulators. Our objective is to identify a list of key ethical issues in pragmatic RCTs and highlight gaps in the ethics literature. Methods We conducted a scoping review of articles addressing ethical aspects of pragmatic RCTs. After applying the search strategy and eligibility criteria, 36 articles were included and reviewed using content (...) analysis. Results Our review identified four major themes: 1) the research-practice distinction; 2) the need for consent; 3) elements that must be disclosed in the consent process; and 4) appropriate oversight by research ethics committees. 1) Most authors reject the need for a research-practice distinction in pragmatic RCTs. They argue that the distinction rests on the presumptions that research participation offers patients less benefit and greater risk than clinical practice, but neither is true in the case of pragmatic RCTs. 2) Most authors further conclude that pragmatic RCTs may proceed without informed consent or with simplified consent procedures when risks are low and consent is infeasible. 3) Authors who endorse the need for consent assert that information need only be disclosed when research participation poses incremental risks compared to clinical practice. Authors disagree as to whether randomization must be disclosed. 4) Finally, all authors view regulatory oversight as burdensome and a practical impediment to the conduct of pragmatic RCTs, and argue that oversight procedures ought to be streamlined when risks to participants are low. Conclusion The current ethical discussion is framed by the assumption that the function of research oversight is to protect participants from risk. As pragmatic RCTs commonly involve usual care interventions, the risks may be minimal. This leads many to reject the research-practice distinction and question the need for informed consent. But the function of oversight should be understood broadly as protecting the liberty and welfare interest of participants and promoting public trust in research. This understanding, we suggest, will focus discussion on questions about appropriate ethical review for pragmatic RCTs. (shrink)

In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment effect. To address the problem of lack of generalizability for the treatment effect estimated by the RCT sample, we leverage observational studies with large samples that are representative of the target population. This article concerns evaluating treatment effects on survival outcomes for a target population (...) and considers a broad class of estimands that are functionals of treatment-specific survival functions, including differences in survival probability and restricted mean survival times. Motivated by two intuitive but distinct approaches, i.e., imputation based on survival outcome regression and weighting based on inverse probability of sampling, censoring, and treatment assignment, we propose a semiparametric estimator through the guidance of the efficient influence function. The proposed estimator is doubly robust in the sense that it is consistent for the target population estimands if either the survival model or the weighting model is correctly specified and is locally efficient when both are correct. In addition, as an alternative to parametric estimation, we employ the nonparametric method of sieves for flexible and robust estimation of the nuisance functions and show that the resulting estimator retains the root- n n consistency and efficiency, the so-called rate-double robustness. Simulation studies confirm the theoretical properties of the proposed estimator and show that it outperforms competitors. We apply the proposed method to estimate the effect of adjuvant chemotherapy on survival in patients with early-stage resected non-small cell lung cancer. (shrink)

BackgroundAccurate reporting on sex and gender in health research is integral to ensuring that health interventions are safe and effective. In Canada and internationally, governments, research organizations, journal editors, and health agencies have called for more inclusive research, provision of sex-disaggregated data, and the integration of sex and gender analysis throughout the research process. Sex and gender analysis is generally defined as an approach for considering how and why different subpopulations (e.g., of diverse genders, ages, and social locations) may experience (...) health conditions and interventions in different or similar ways.The objective of this study was to assess the extent and nature of reporting about sex and/or gender, including whether sex and gender analysis (SGA) was carried out in a sample of Canadian randomized controlled trials (RCTs) with human participants.MethodsWe searched MEDLINE from 01 January 2013 to 23 July 2014 using a validated filter for identification of RCTs, combined with terms related to Canada. Two reviewers screened the search results to identify the first 100 RCTs that were either identified in the trial publication as funded by a Canadian organization or which had a first or last author based in Canada. Data were independently extracted by two people from 10% of the RCTs during an initial training period; once agreement was reached on this sample, the remainder of the data extraction was completed by one person and verified by a second.ResultsThe search yielded 1433 records. We screened 256 records to identify 100 RCTs which met our eligibility criteria. The median sample size of the RCTs was 107 participants (range 12–6085). While 98% of studies described the demographic composition of their participants by sex, only 6% conducted a subgroup analysis across sex and 4% reported sex-disaggregated data. No article defined “sex” and/or “gender.” No publication carried out a comprehensive sex and gender analysis.ConclusionsFindings highlight poor uptake of sex and gender considerations in the Canadian RCT context and underscore the need for better articulated guidance on sex and gender analysis to improve reporting of evidence, inform policy development, and guide future research. (shrink)

Aims and background: Little is known about how participants perceive prevention trials, particularly trials designed to prevent mental illness. This study examined participants’ motives for participating in a trial and their views of randomisation and the ability to withdraw from a randomised controlled trial for prevention of depression. Methods: Participants were older adults reporting elevated depression symptoms living in urban and regional locations in Australia who had consented to participate in an RCT of interventions to prevent depression. (...) Participants rated their agreement with various statements describing motivations for enrolment in the trial and opinions regarding randomisation and withdrawal. Results: The majority of participants expressed a triad of altruistic motivation for participation, relative lack of concern about randomisation and commitment to the trial. Certain subgroups of participants, such as women and those with higher depression scores, reported higher levels of concern about specific issues. Conclusions: The findings suggest that participants enrolled in prevention trials for mental illness are likely to hold positive attitudes towards research trials. The identification of relationships between key person factors and trial-related attitudes enabled profiling of participant groups, which can inform recruitment strategies and interactions of participants and research projects in future prevention trials. (shrink)

This article uses the case of “social impact bonds” (SIBs) to explore the role of social science methods in new markets in “social investment.” Pioneered in the UK in 2010, SIBs use private capital to fund social programs with governments paying returns for successful outcomes. Central to the SIB model is the question of evaluation and the method to be used in determining program outcomes and investor returns. In the United States, the randomized controlled trial (RCT) has been (...) the dominant method. However, this has not been without controversy. Some SIB practitioners and investors have argued that, while this may be the perfect tool, the need to grow the SIB market demands a more pragmatic approach. Drawing from a three-year study of SIBs, and informed by Science and Technology Studies (STS)-inspired work on valuation and the social life of methods, the article explores RCTs as both a valuation technology central to SIB design and the object of a micropolitics of valuation which has impeded market growth. It is the relationship between, and the politics of, evaluation and valuation that is a key lesson of the SIB experiment and an important insight for future research on “social investment” and other settings where methods are constitutive of financial value. (shrink)

BackgroundIndividuals with early phase cognitive impairment are frequently affected by existential distress, social avoidance and associated health issues. The demand for efficient psychological support is crucial from both an individual and a societal perspective. We have developed a novel psychological intervention manual for providing a non-medical path to enhanced psychological health in the cognitively impaired population. The current article provides specific information on the randomized controlled trial -design and methods. The main hypothesis is that participants receiving PIPCI will (...) increase their psychological flexibility compared to participants in the active control group and the waiting list control group. The secondary hypotheses are that participants receiving PIPCI will improve psychological health compared to participants in the active control group and the waiting list control group.Materials and MethodsThis three-arm RCT will recruit participants from the cognitive centers at Karolinska University Hospital in Stockholm and randomize approximately 120 individuals in the early phase of cognitive impairment to either an experimental group, an active control group or a waiting list control group. Intervention outcome will be evaluated with self-report questionnaires on physical and psychological aspects of health, cognitive assessment, biological markers and health care costs. Assessments will be performed at pre- and post-intervention, as well as at a 6-month follow-up.DiscussionThe development of a potentially feasible and effective psychological intervention tailored for early phase cognitive impairment has the potential to advance the non-pharmacological intervention field. This is especially important given the extensive burden for many affected individuals and their families and the current lack of effective treatments. If the psychological intervention discussed here shows feasibility and efficacy, there is potential for far-reaching healthcare implications for patients with early cognitive impairment at risk of developing dementia.Clinical Trial RegistrationClinicalTrials.gov: NCT04356924. Date of registration: April 22, 2020. URL: https://clinicaltrials.gov/ct2/show/NCT04356924. (shrink)

ObjectiveThis study aimed to examine the effectiveness and safety of the Brain-computer interface in treatment of upper limb dysfunction after stroke.MethodsEnglish and Chinese electronic databases were searched up to July 2021. Randomized controlled trials were eligible. The methodological quality was assessed using Cochrane’s risk-of-bias tool. Meta-analysis was performed using RevMan 5.4.ResultsA total of 488 patients from 16 RCTs were included. The results showed that the meta-analysis of BCI-combined treatment on the improvement of the upper limb function showed (...) statistical significance [standardized mean difference : 0.53, 95% CI: 0.26–0.80, P < 0.05]; BCI treatment can improve the abilities of daily living of patients after stroke, and the analysis results are statistically significant ; and the BCI-combined therapy was not statistically significant for the analysis of the Modified Ashworth Scale.ConclusionThe meta-analysis indicates that the BCI therapy or BCI combined with other therapies such as conventional rehabilitation training and motor imagery training can improve upper limb dysfunction after stroke and enhance the quality of daily life. (shrink)

Background: People with traumatic brain injury face a range of mental health challenges during the adjustment process post-injury, but access to treatment can be difficult, particularly for those who live in regional and remote regions. eHealth provides the potential to improve access to evidence-based psychological therapy for people with a severe TBI. The aim of the current study is to assess the efficacy of a psychological intervention delivered via video consulting to reduce psychological distress in people with TBI.Methods: This paper (...) outlines the protocol for a multi-center, three-arm, parallel, non-inferiority randomized controlled trial of an evidence-based manualized psychological intervention, ACT-Adjust. ACT-Adjust provides nine sessions for adults with a moderate to severe TBI experiencing clinical levels of psychological distress. Fifty-six participants referred from Brain Injury Rehabilitation Units across New South Wales and the NSW icare scheme will be randomly allocated to three conditions; video consulting, face-to-face and, a waitlist control.Discussion: This is the first RCT to evaluate the efficacy of a psychological therapy delivered via video consulting for individuals with a moderate to severe TBI.Trial Registration:www.anzctr.org.au, Australian New Zealand Clinical Trials Registry ANZCTRN2619001602112. (shrink)

Madole & Harden's assertion that the effects derived from within-family genome-wide association studies (GWASs) and from randomized controlled trials (RCTs) are equivalent is misleading. GWASs are substantially more “non-unitary, non-uniform, and non-explanatory” than RCTs. While the within-family GWAS bring us closer to identifying genetic causes, whether it will change behavioral genetics into a causal science is an open question.

Objective: To systematically analyze the effectiveness of technology-based interventions for reducing loneliness in older adults.Methods: We searched relevant electronic databases from inception to April 2021, which included Cochrane Library, PubMed, Web of Science, SpringerLink, EMBASE, CNKI, and Wanfang. The following criteria were used: study design—randomized controlled trial designs, people—older adults, intervention—technology-based interventions in which a core component involved the use of technology to reduce loneliness in older adults; and outcome—reduction of loneliness level in terms of rating scale scores. (...) Two reviewers independently identified eligible studies, extracted data, and assessed the risk of bias in the included studies. A third reviewer resolved any conflicts. The Cochrane Collaboration's bias assessment tool was used to evaluate the risk of bias for the included studies, and Review Manager 5.4 software was used for the meta-analysis. A random effects model was adopted to measure estimates of loneliness reduction, and standard mean differences with a 95% confidence interval were calculated for each intervention-control contrast, and the I2 statistic was applied to examine heterogeneity.Results: A total of 391 participants from six RCTs were included in the review. Of these, three studies were rated as low-quality, and the remaining three were rated as moderate-quality studies. The meta-analysis showed that the evidence regarding the effects on loneliness of technology-based interventions compared with control groups was uncertain, and suggested that technology-based interventions resulted in little to no difference in loneliness reduction compared to control groups. Two types of technology-based interventions were identified: smartphone-based video calls and computer-based training with Internet usage. The subgroup analysis found low-quality evidence to support the effectiveness of both intervention types.Conclusions: We found no current evidence to support that technology-based interventions were effective compared to different control conditions in reducing loneliness in older adults. This suggests that more research is needed to investigate the effects of technology-based interventions on loneliness in older adults. (shrink)

Objectives: This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to improve subjective well-being (SWB), including evaluative, hedonic, and eudemonic well-being, and the mental component of quality of life (QOL) of working population. Methods: A literature search was conducted, using PubMed, Embase, PsycINFO, and PsycARTICLES. Eligible studies included those that were RCTs of any intervention, conducted among healthy workers, measured SWB as a primary outcome, and original articles in English. Study characteristics, (...) intervention, outcomes, and results on SWB outcomes were extracted by the investigators independently. After a brief narrative summarizing and classifying the contents of the interventions, the included outcomes were categorized into each aspect of SWB (evaluative, hedonic, and eudemonic well-being, and the mental component of QOL). Finally, the characteristics of the effective interventions for increasing each aspect were summarized, and the pooled effect of interventions on SWB was investigated by a meta-analysis. Publication bias was investigated by drawing a funnel plot and conducting Egger's test. Results: From the 5,450 articles found, 39 met the inclusion criteria for the systematic review. The interventions included in this review were classified into six categories (physical activity, ergonomics, psychological, environmental, multicomponent intervention, and others). The meta-analysis from 31 studies showed that the pooled effect of included interventions on SWB was significantly positive (standardized mean difference (SMD) = 0.51; standard error (SE) = 0.10). A funnel plot showed there were extremely large or small SMDs, and Egger's test was significant. Thus, we conducted sensitivity analysis, excluding these extreme SMDs, and confirmed that the estimated pooled effect was also significantly positive. Subgroup analyses for separate types of interventions showed the effects of psychological interventions (e.g., mindfulness, cognitive behavioral based approach, and other psychological interventions) were also significantly positive. Conclusion: The current study revealed the effectiveness of interventions for increasing SWB. Specifically, psychological interventions (e.g., mindfulness, cognitive behavioral based approach, and other psychological interventions) may be useful for improving SWB. (shrink)

BackgroundIn many Western countries like Germany, the social integration of children with an immigrant background has become an urgent social tasks. The probability of them living in high-risk environments and being disadvantaged regarding health and education-related variables is still relatively higher. Yet, promoting language acquisition is not the only relevant factor for their social integration, but also the support of earlier developmental processes associated with adequate early parenting in their first months of life. The Emotional Availability Scales measure the quality (...) of caregiver-child-interactions as an indicator of the quality of their relationship and thus of such early parenting, focusing on mutual and emotional aspects of their interaction.MethodThis pilot study examined in a randomized controlled trial the effects of the prevention project First Steps regarding the hypothesis that the Emotional Availability improved to a greater extent in “difficult-to-reach” immigrant mother-child dyads in a psychoanalytically oriented early intervention compared to a usual care intervention offered by paraprofessionals with an immigrant background. A sample of N = 118 immigrant women in Germany from 37 different countries and their children was compared with regard to the parental EA-dimensions sensitivity, structuring, non-intrusiveness and non-hostility and the child dimensions responsiveness to and involvement of the caregiver in the pre-post RCT design.Results and ConclusionDifferent from what was expected, repeated ANOVAs revealed no significant pre-post group differences for the parental dimensions. For the child dimensions the effect of time of measurement was highly significant, which can be interpreted as mostly natural developmental effects. Still, on the level of simple main effects for each intervention, only in the FIRST STEPS groups child responsiveness significantly improved. When controlled for confounding variables, a significant interaction effect for maternal sensitivity in favor of the FIRST STEPS intervention was found. The systematic group differences indicate that the more extensive and professional intervention, focusing on the individual needs of the participants, is more suitable to support the quality of the mother-child-relationship amongst immigrant mother-child dyads than usual care. The results are discussed taking into account the context of the maternal migration process and potential maternal traumatization.Clinical Trial Registration[https://clinicaltrials.gov], identifier [DRKS00004632]. (shrink)

Policies to combat climate change should be supported by evidence regarding their effectiveness. But what kind of evidence is that? And what tools should one use to gather such evidence? Many argue that randomized controlled trials are the gold standard when it comes to evaluating the effects of policies. As a result, there has been a push for climate change policies to be evaluated using RCTs. We argue that this push is misguided. After explaining why RCTs are (...) thought to be the gold standard, we use examples of mitigation and adaptation policies to show that RCTs provide, at best, one piece of the evidential puzzle one needs to assemble for well-supported decisions regarding climate change policies. (shrink)

BackgroundEarly in the COVID-19 pandemic, the urgent need to discover effective therapies for COVID-19 prompted questions about the ethical problem of randomization along with its widely accepted solution: equipoise. In this scoping review, uses of equipoise in discussions of randomized controlled trials of COVID-19 therapies are evaluated to answer three questions. First, how has equipoise been applied to COVID-19 research? Second, has equipoise been employed accurately? And third, do concerns about equipoise pose a barrier to the ethical (...) conduct of COVID-19 RCTs?MethodsGoogle Scholar and Pubmed were searched for articles containing substantial discussion about equipoise and COVID-19 RCTs. 347 article titles were screened, 91 full text articles were assessed, and 48 articles were included. Uses of equipoise were analyzed and abstracted into seven categories.Results and discussionApproximately two-thirds of articles used equipoise in a way that is consistent with the concept. They invoked equipoise to support RCTs of specific therapies, RCTs in general, and the early termination of RCTs after achieving the primary outcome. Approximately one-third of articles used equipoise in a manner that is inconsistent with the concept. These articles argued that physician preference, widespread use of unproven therapies, patient preference, or expectation of therapeutic benefit may undermine equipoise and render RCTs unethical. In each case, the purported ethical problem can be resolved by correcting the use of equipoise.ConclusionsOur findings highlight the continued relevance of equipoise as it supports the conduct of well-conceived RCTs and provides moral guidance to physicians and researchers as they search for effective therapies for COVID-19. (shrink)

BackgroundAt present, adherence to antipsychotic treatment is often poor, leading to the recurrence of symptoms. This increases the likelihood of the patient experiencing disability and thus increases the disease burden for the patient, their family, and society as a whole. However, to date, there is no clear evidence regarding the effect of medication adherence interventions on outcomes for patients with schizophrenia. Moreover, the traditional intervention methods are limited by manpower and resources in low- and middle-income countries. Recent studies have demonstrated (...) that increasing a patient’s level of self-compassion may improve their treatment adherence. Online mental health care interventions have advantages in terms of feasibility and acceptability for patients with schizophrenia. In this regard, a WeChat-based self-compassion training protocol to improve patient treatment adherence was designed in this study and will be evaluated in the future to determine its impact on patients with schizophrenia.MethodsThe protocol for the randomized controlled trial is based on the SPIRIT 2013 statement. This parallel RCT will aim to recruit 392 patients with schizophrenia who will be randomized at a 1:1 ratio into a 3-week intervention or control group. Both groups will receive routine care. The intervention group will also receive WeChat-based self-compassion training, which requires participants to complete three tasks every day, including a reading task, a meditation task, and a self-compassion journal task. The control group will receive WeChat-based psychological health education, which will only require participants to read positive articles about psychological health every day. Medication adherence, self-compassion, stigma, and social support will be measured at baseline, immediately after the intervention, and 3 weeks after the intervention. Program feasibility will be evaluated throughout the course of the study, and acceptability will be measured immediately after the intervention.Expected results:The intervention described here will address the barriers to accessing mental health care for people with schizophrenia, including patients’ desire for independent management, difficulty accessing providers, and concerns about privacy and stigma. The current study provides guidance for clinical nurses to carry out psychological intervention, with the ultimate aim of addressing the problems associated with a shortage of psychological professionals in low- and middle-income countries. (shrink)

The current controversy as to the proper role of the placebo control in the evaluation of new treatments for schizophrenia requires an analysis that is sensitive to both ethical and scientific issues. Clinical equipoise, widely regarded as the moral foundation of the randomized controlled trial (RCT), requires the use of best available treatment as the control in RCT. Scientific criticisms of the use of an active control are examined and none present an insuperable barrier to the use of (...) an active control. Indeed, scrutiny of the most recent argument for the use of placebo controls, 'assay sensitivity', suggests that the use of placebo may be the cause of the problem pointed to. Scientific, regulatory, ethical and legal advantages of the use of an active control are described. While the use of a placebo control may be acceptable in carefully defined circumstances, in most cases the use of an active control in schizophrenia research is ethically and scientifically preferable. (shrink)

Background Previous reports have described that simple cognitive training using reading aloud and solving simple arithmetic calculations, so-called “learning therapy”, can improve executive functions and processing speed in the older adults. Nevertheless, it is not well-known whether learning therapy improve a wide range of cognitive functions or not. We investigated the beneficial effects of learning therapy on various cognitive functions in healthy older adults. Methods We used a single-blinded intervention with two groups (learning therapy group: LT and waiting list control (...) group: WL). Sixty-four elderly were randomly assigned to LT or WL. In LT, participants performed reading Japanese aloud and solving simple calculations training tasks for 6 months. WL did not participate in the intervention. We measured several cognitive functions before and after 6 months intervention periods. Results Compared to WL, results revealed that LT improved inhibition performance in executive functions (Stroop: LT (Mean = 3.88) vs. WL (Mean = 1.22), adjusted p =.013 and reverse Stroop LT (Mean = 3.22) vs. WL (Mean = 1.59), adjusted p =.015), verbal episodic memory (logical memory: LT (Mean = 4.59) vs. WL (Mean = 2.47), adjusted p =.015), focus attention(D-CAT: LT (Mean = 2.09) vs. WL (Mean = -0.59), adjusted p =.010) and processing speed compared to the waiting list control group (digit symbol coding: LT (Mean = 5.00) vs. WL (Mean = 1.13), adjusted p =.015 and symbol search: LT (Mean = 3.47) vs. WL (Mean = 1.81), adjusted p =.014). Discussion This RCT can showed the benefit of learning therapy on inhibition of executive functions, verbal episodic memory, focus attention, and processing speed in healthy elderly people. Our results were discussed under overlapping hypothesis. Trial registration “This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (UMIN000006998).”. (shrink)

Background Disclosure of obtaining informed consent from patients (ICP) and research ethics committee (REC) approval in published reports is sometimes omitted. To date, no disclosure data are available on surgical research. Objective Our aim was to assess whether REC approval and ICP were documented in surgical trials. Study design Overall, 657 randomised trials, published between 2005 and 2010 in 10 international journals, were included. We collected the report rate of REC approval and ICP and contacted the corresponding author (...) when ethical information was lacking. Results Among the 657 randomised controlled trials (RCT), 576 (87.7%) stated that an REC had approved the research, and 606 (92.2%) stated that ICP had been requested. Furthermore, 28 RCTs (4.3%) reported neither REC nor ICP. Conclusions The phase III randomised surgical trials that were analysed were shown to have respected fundamental ethical principles in approximately 90% of the cases examines. (shrink)

Objective: This study examined whether patients who were randomly assigned to their preferred therapy arm had stronger engagement with their treatment than those who were randomly assigned to a non-preferred therapy arm.Method: Data were drawn from a RCT comparing Individual Meaning-Centered Psychotherapy, with Individual Supportive Psychotherapy, in patients with advanced cancer. Treatment engagement was operationalized as patients' perceptions of the therapeutic alliance with their therapist and therapy sessions attended. Two 2 by 2 Analysis of Variance models were used, with treatment (...) preference and treatment assignment as the independent variables and working alliance and number of sessions attended as outcome variables.Results: Patients who preferred and were assigned to IMCP reported a significantly stronger alliance than those who preferred IMCP but were assigned to ISP.Conclusions: The findings from this study have broader implications for research on psychotherapy beyond the appeal of IMCP in advanced cancer patients. Patients who prefer a novel psychotherapy that they cannot engage in elsewhere, but receive the standard treatment may experience weaker alliance than patients who prefer the standard but receive the novel therapy.Trial registration:Clinicaltrial.gov ID: NCT01323309. (shrink)

Background: Chronic Pain (CP) has serious medical and social consequences, and leads to economic burden that threatens the sustainability of healthcare services. Thus, optimized management of pain tools to support CP patients in adjusting to their condition and improving quality of life is timely. Although Acceptance and Commitment Therapy (ACT) is considered an evidence-based psychological approach for CP, evidence for the efficacy of online-delivered ACT for CP is still scarce. At the same time, studies suggest that self-compassion mediates the change (...) in disability and psychopathological symptoms in ACT interventions for CP, although self-compassion is not a specific target in ACT. Thus, an explicit focus on self-compassion might increase the efficacy of ACT interventions for CP, although this hypothesis has not been tested. This study aims to develop an eHealth ACT and compassion-based self-management intervention for CP, the iACTwithPain, and to compare its efficacy in improving health outcomes to a similar ACT-only intervention and a waiting list group. Methods: The eHealth platform that will host the interventions will be developed using a flat design identity and will be interactive. The iACTwithPain intervention will comprise 8 weekly self-management sessions, and will be developed taking into consideration the psychological flexibility model applied to CP, with the addition of explicit compassion-based components. To analyse whether the iACTwithPain intervention will present superiority in improving CP’s impact and related health markers over the two other conditions, this study will follow a RCT design with three arms. CP patients will be recruited through direct contact with patient associations and healthcare services and a national press release in Portugal. Outcome measurement will be conducted at baseline, post-intervention and at 3- and 6-months follow-ups. The interventions’ acceptability will also be assessed. Discussion: The iACTwithPain intervention is expected to improve CP patients’ psychosocial functioning, quality of life, and empowerment, by promoting adaptive disease management and regulation of pain-related internal experiences. Results will contribute to a better understanding on the pertinence of adding compassion elements to ACT for CP and to reach an optimized intervention for CP. (shrink)

In 1995, the Dutch Minister of Health proposed that a randomized clinical trial (RCT) with heroin-maintenance for severe abusers be conducted. It took nearly four years of lengthy debates before the Dutch Parliament consented to the plan. Apart from the idea of prescribing heroin, the minister and her scientific advisers had to defend the quite high material and non-material costs that would arise from employing the randomized controlled design. They argued that the RCT represented the truly scientific (...) approach and was the royal way to unambiguous results. In the present article, I question this common dual justification of RCTs. First, I situate the historical origins and the basic assumptions of the ideal experiment in 20th-century economic liberalism. Secondly, using the Dutch heroin experiment as an example, I discuss human-science experimentation as an attempt to create reality rather than merely record it. Finally, I discuss some surprising responses by heroin users. These responses display the assumptions of RCTs discussed in the historical section, and underline the importance of the culture of heroin use. In the epilogue, I suggest that cultural aspects of heroin consumption can best be studied by thorough ethnographic research. (shrink)

Little is known about the views of mothers when their children are invited to participate in randomized clinical trials (RCTs) investigating medicines and/or invasive procedures. Our goal was to understand mothers’ perceptions of the processes of informed consent and randomization in a RCT that divided uncooperative children into three intervention groups (physical restraint, sedation, and general anesthesia) for dental rehabilitation.

One of the well-established methodological approaches in contemporary medicine is the Evidence Based Medicine (EBM) model. There are two methodological ideas that support this model: hierarchy of evidence and Randomised Controlled Trials (RCT’s). In this work, I will present the examples that are standing out of the EBM model explanatory power. I will also show the methodological power of the EBM model into the process of diagnosis and treаtment in contemporary medicine. One of the important problems in the (...) field of philosophy of science will be used to present the anomalies problem in medical theories. The anomalies problem presented as a methodological problem of the EBM model is an open discussion concerning paradigm change in medicine. At the end of the paper some other ideas about progress in medicine will be put in for consideration. (shrink)

Governments are increasingly using randomized controlled trials (RCTs) to evaluate policy interventions. RCTs are often understood to provide the highest quality evidence regarding the causal efficacy of an intervention. While randomization plays an essential epistemic role in the context of policy RCTs however, it also plays an important distributive role. By randomly assigning participants to either the intervention or control arm of an RCT, people are subject to different policies and so, often, to different types and levels (...) of benefits. In this paper, I identify one necessary condition as well as a set of sufficient conditions for the permissible use of random assignment by government agencies. I argue first that random assignment is permissible only if it is consistent with governments’ duty to realize morally important outcomes. I argue second that random assignment is permissible in cases where investigators are in a state of genuine equipoise regarding all arms of the experiment and the policy to which people have a claim of justice. Finally, I defend a set of conditions under which random assignment is permissible in cases where one or more arms of a policy RCT are reasonably expected to be either superior or inferior to this policy. (shrink)