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Background Sham acupuncture is a widely accepted control in acupuncture clinical trials. Given the nature of acupuncture, it is warranted to assess the blinding of sham-controlled trials. Despite the sham acupuncture design having been widely used, the overall blinding of sham acupuncture and the characteristics of blinding assessment in acupuncture trials are unclear. This research aims to assess the blinding status of acupuncture clinical trials and explore the blinding assessment characteristics in acupuncture trials. Methods This meta-analysis included all the acupuncture clinical trials published in English that performed blinding assessments and reported the results. We searched PubMed, Embase, and Web of Science for randomized controlled trials (RCTs) from inception to April 2024. The primary outcome is Bang’s Blinding Index (Bang’s BI) and 95% credibility interval (CrI) was pooled using a Bayesian hierarchical model. The study adheres to the PRISMA guidelines. Results Sixty-four eligible studies published from 1999 to 2024 were included. The mean of Bang’s BI was − 0.24 (95% CrI − 0.34 to − 0.14, tau 2  = 0.13) for the sham acupuncture group and 0.41 (95% CrI 0.32 to 0.49, tau 2  = 0.10) for the verum acupuncture group. The characteristics of blinding showed that 62.50% of the trials had a Bang’s BI greater than 0 in the verum group and less than 0 in the sham group; in 28.15% of the trials, the Bang’s BI was greater than 0 in the verum group and greater than 0 in the sham group. Subgroup analysis revealed that area, number of research centers, treatment sessions, acupoints number, and evaluation timepoint can influence blinding results. Conclusion Overall blinding status in current acupuncture clinical trials shows a majority correctly guessing for the verum group and opposite guessing for the sham group. However, in some acupuncture trials, the blinding of sham acupuncture might be compromised. Factors such as the Asian population, penetrating sham needling, and querying participants about their group assignment during the study increase the risk of unblinding and warrant careful consideration in sham acupuncture control design. Furthermore, researchers should closely monitor the blinding status of sham acupuncture and transparently report details of blinding assessments. Systematic review registration PROSPERO CRD42023403595.

Blinding mitigates several sources of bias which, if left unchecked, can quantitively affect study outcomes. Blinding remains under-utilized, particularly in non-pharmaceutical clinical trials, but is often highly feasible through simple measures. Although blinding is generally viewed as an effective method by which to eliminate bias, blinding does also pose some inherent limitations, and it behooves clinicians and researchers to be aware of such caveats. This article will review general principles for blinding in clinical trials, including examples of useful blinding techniques for both pharmaceutical and non-pharmaceutical trials, while also highlighting the limitations and potential consequences of blinding. Appropriate reporting on blinding in trial protocols and manuscripts, as well as future directions for blinding research, will also be discussed.

Background Studies in animal models and humans with type 1 diabetes mellitus (T1DM) have shown that probiotic supplementation leads to decreased pro‐inflammatory cytokines (responsible for damaging β‐cells of the pancreas), improved gut barrier function, and induction of immune tolerance. Objective To study the effect of supplementation of probiotics in children with T1DM on glycemic control, insulin dose, and plasma C‐peptide levels. Methods A single‐centered, double‐blinded, and randomized placebo‐controlled pilot trial was conducted in children (2–12 years) with new‐onset T1DM. Ninety‐six children were randomized and allocated to Placebo or Intervention groups. The intervention included high dose (112.5 billion viable lyophilized bacteria per capsule) multi‐strain probiotic De Simone formulation (manufactured by Danisco‐Dupont) sold as Visbiome® in India. The probiotic was supplemented for 3 months and HbA1c, fasting C‐peptide, blood sugar records, and insulin dose was recorded at baseline and 3 months. Results A total of 90 patients (45 in each group) were analyzed for outcome parameters. We found a significant decrease in HbA1c (5.1 vs. 3.8; p = 0.021) and a significant decline in total and bolus insulin dose (U/kg/day; p = 0.037 and 0.018, respectively) in the intervention group when compared with the placebo group. A significantly higher (p = 0.023) number of children achieved remission in the treatment group. We did not notice adverse effects in either of the study groups. Conclusion Children with newly diagnosed T1DM managed with standard treatment along with probiotics showed better glycemic control and a decrease in insulin requirements; however, more extensive studies are further warranted.

Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect. Psychedelic psychotherapy, therapy enhanced with psychedelic drugs such as LSD or psilocybin (the active ingredient of ‘magic mushrooms’), has been suggested to improve psychological well-being. For this reason, trials on psychedelic therapy for the treatment of depression, addiction and other conditions are ongoing. Recently, ‘microdosing’ – a way of administering psychedelics that involves taking about 10% of a recreational dose two or three times per week – has gained popularity. Unlike taking large doses of psychedelics, microdosing does not induce hallucinations, but anecdotal reports suggest that it yields similar benefits as psychedelic therapy. A key feature of modern medicine are ‘placebo control’ studies that compare two groups of patients: one that takes a drug and another that takes inactive pills, known as placebos. Crucially, neither group knows whether they are taking drug or placebo. This control ensures that observed effects are due to the drug itself and not to unrelated psychological causes. For example, in trials of mood medicines, participants often expect to feel happier, which in itself improves their mood even when taking a placebo. This is known as the placebo effect. Restrictive drug policies make placebo-controlled studies on psychedelics difficult and expensive, in particular for microdosing, which involves taking psychedelics over a longer time period. To overcome this problem, Szigeti et al. developed a new citizen-science approach, where microdosers implemented their own placebo control based on online instructions. The advantages are the low cost and the ability to recruit participants globally. The experiment was completed by 191 microdosers, making it the largest placebo-controlled study on psychedelics to-date, for a fraction of the cost of an equivalent clinical study. The trial examined whether psychedelic microdosing can improve cognitive function and psychological well-being. The team found that microdosing significantly increased a number of psychological measures, such as well-being and life satisfaction. However, participants taking placebo also improved: there were no significant differences between the two groups. The findings confirmed positive anecdotes about microdosing improving people’s moods, but at the same time show that taking empty capsules, knowing they might be microdoses, have the same benefits. This result suggests that the observed benefits are not caused by the microdose, but rather by psychological expectations. The study’s innovative ‘do-it-yourself’ approach to placebo control may serve as a template for future citizen science studies on other popular phenomena where positive expectations and social factors could play a role, such as cannabidiol (CBD) oils, nootropics and nutrition.

In the GRADE approach, randomized trials start as high-quality evidence and observational studies as low-quality evidence, but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias. Well-established limitations of randomized trials include failure to conceal allocation, failure to blind, loss to follow-up, and failure to appropriately consider the intention-to-treat principle. More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results. Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance. Risk of bias may vary across outcomes (e.g., loss to follow-up may be far less for all-cause mortality than for quality of life), a consideration that many systematic reviews ignore. In deciding whether to rate down for risk of bias—whether for randomized trials or observational studies—authors should not take an approach that averages across studies. Rather, for any individual outcome, when there are some studies with a high risk, and some with a low risk of bias, they should consider including only the studies with a lower risk of bias.

Tactical Edge Networks (TENs) serve as critical infrastructure for disseminating time-sensitive intelligence under resource-constrained and hostile conditions such as Network-Centric Warfare (NCW) and the Internet of Battlefield Things (IoBT), where secure and efficient data sharing is a core requirement. To ensure security and privacy in such environments, strict adherence to the ”need-to-know” principle is imperative, requiring that sensitive mission data are accessible only to entities with specific authorization attributes. Ciphertext-Policy Attribute-Based Encryption (CP-ABE) binds fine-grained access policies to ciphertexts and permits decryption only for attribute-satisfying users, rendering it inherently suitable for need-to-know control in these settings. However, the prohibitive computational overhead of bilinear pairings in CP-ABE is often impractical for lightweight frontline terminals in tactical edge networks. While outsourcing decryption to Tactical Cloud Nodes (TCNs) can alleviate this burden, it brings critical vulnerabilities in zero-trust deployments, including key exposure upon node capture, incorrect computation results, and the leakage of query intent to an honest-but-curious Command Center (CC). To address these issues, we present a novel resilient and verifiable outsourced attribute-based non-interactive oblivious transfer protocol. The proposed framework balances system efficiency with security and privacy, as well as addresses the inherent computational asymmetry between resource-constrained tactical edge devices and powerful cloud nodes. We integrate a receiver-privacy-only, NIOT-style index-hiding mechanism (RP-NIOT) into an offline/online encryption pipeline to conceal the user’s query index from an honest-but-curious command center (CC). We do not claim classical OT sender privacy; unauthorized-record confidentiality is enforced by the CP-ABE/KEM–DEM layer. In addition, we incorporate a user-held blinding factor into the transformation keys to decouple the outsourcing capability from final decryption to ensure resilience against TCN compromise. A novel lightweight hash-based verification mechanism is designed to guarantee the correctness of outsourced computations. Detailed security and efficiency analysis show that the proposed protocol achieves resilience and data confidentiality as well as other security objectives at a cost of constant (policy-size independent) online terminal overhead—dominated by two exponentiations (plus one inversion), one MAC verification, two hash/KDF evaluations, and one symmetric decryption per query—making it suitable for latency-sensitive tactical applications.

Randomized clinical trials often serve the purpose of assessing the efficacy and safety of a compound. By combining real-world evidence and randomization, pragmatic randomized clinical trials (PrCTs) can be used to inform treatment effectiveness and healthcare decisions. PrCTs, referring to studies where several pragmatic elements are used (eligibility, endpoints, follow-up, etc.), pose unique challenges (Loudon et al. in BMJ 350:h2147, 2015). From a literature review, we propose a definition of PrCT and discuss strategies to overcome some PrCT challenges. Use of alternative data collection approaches may lead to uncertainties, and absence of blinding could potentially lead to non-random missing data at study endpoints such that randomization is no longer protected by an intent to treat. Therefore, more complex randomization strategies may be needed to minimize bias. Additional data sources could be used to synthesize information and create a more accurate endpoint definition, which may require tools such as natural language processing. The statistician must become familiar with the challenges and strengths of PrCTs, ranging from design to analysis to interpretation, in order to transform data into evidence (Califf in Clin Trials 13:471–477, 2016).

Introduction: Quality assessment of randomized controlled trials (RCTs) is important to prevent clinical application of erroneous results. Materials and Methods: This was an assessment of published RCTs in surgical subspecialties during 2011-2018 based on MEDLINE and EMBASE search. The primary objective of the present study was to quantitatively and qualitatively analyze the RCTs published from India based on year of publication, geographical distribution, and subspecialty using the modified Jadad score (high quality if score is ≥3; or ≥2 if blinded design was not feasible). Its secondary objective was to identify factors affecting the quality of RCTs. Results: Among 1304 trials identified, 162 were analyzed. Of these 96 (59%) had a score of ≥3; and 104 (64.2%) were of high quality (score ≥2). Year-wise there was no significant quantitative (P = 0.329) or qualitative (P = 0.255) variation. Geographic regions had similar quantity (P = 0.206) and quality (P = 0.068). The RCTs among subspecialties too were comparable in quantity and quality. Higher impact factor of journal (P = 0.013) and assessment by Institute Review Board (IRB) (P = 0.004) were significantly associated with a better study quality. Type of institution, number of authors, centricity, assistance by a statistician, and source of funding did not affect the quality of RCTs. Conclusions: The quantity and quality of surgical RCTs were stable and comparable over the years and across geographical regions and subspecialties. Higher impact factor of journal and review by IRB were significantly associated with a better study quality.

Pragmatic trials are increasingly gaining recognition. However, what pragmatic trials are is frequently misunderstood. They are frequently described superficially by their manifestation and surface only, as studies conducted in “real world” settings, having wide inclusion criteria, and less complicated study procedures. However, these features are neither necessary nor defining characteristics. They also do not guarantee that trials sharing them are useful to inform medical practice. There is a danger of losing sight of the essence of the powerful pragmatic approach. Here we describe the key elements of the pragmatic approach and the close relationship with the original nature of randomized trials. Our aim is to refocus teaching, research and interpretation of evidence, not as a novel approach but as a return towards the essence of pragmatic evidence and the nature of randomized trials. We first go back to the origin of pragmatism in philosophy and its introduction in medicine and revisit the nature of randomized trials in their pure form. We highlight the critical distinction between assessing treatment decisions and understanding the mechanisms of these decisions. We show why the current view on randomized trials in medicine has lost a pragmatic focus, with the explanatory design features blinding and adherence control often seen as defining characteristics or quality criteria of randomized trials. We then highlight common misunderstandings of pragmatic trials and conclude with an overview of their key features to provide pragmatic evidence. Key•Knowing what is form and what is function avoids misconceptions about pragmatic trials.•Trials are not simply pragmatic due to their integration into routine care.•The nature of RCTs is not testing interventions with controls but comparing decisions.•Avoiding blinding or adherence control, often used by explanatory trials, eases conduct but does not define design.•Pragmatic randomized trials compare real-world decisions on practical outcomes.

The Villum Experiment (VEX) is one of the few funding schemes that employs a double-blind review process where applicants are blinded to reviewers, applications are highly standardized, reviewers do not deliberate, and funding is determined solely by ranked aggregated review scores. This unique controlled setting enables assumptions that direct reviewer gender bias is highly unlikely. Using a causal framework (DAG), we examine the extent to which gender disparities in funding may exist in such a setting. Our analyses of 2,041 applications from five funding rounds (2017–2021) reveal a small but consistent gender disparity in success rates, concentrated within the Life Science panel. As reviewer bias is unlikely in this setting, these disparities or structural inequalities are likely caused by differences in gender compositions across disciplines and the underrepresentation of highly experienced women among the applicants and in the population in general. Multilevel modeling with poststratification indicates that accounting for these structural factors removes the disparity in funding success rates. Our findings highlight that gender disparity in funding may remain without direct review bias. In this case, such remaining disparities are likely rooted in broader structural inequalities within academia and/or compositional effects.