High-cited favorable studies for COVID-19 treatments ineffective in large trials

Clinical Studies ◽

Observational Studies ◽

Randomized Trials ◽

Controlled Trials ◽

Randomized Controlled ◽

Wide Dissemination ◽

Highly Cited Articles ◽

Highly Cited

Importance. COVID-19 has resulted in massive production, publication and wide dissemination of clinical studies trying to identify effective treatments. However, several widely touted treatments failed to show effectiveness in large well-done randomized controlled trials (RCTs). Objective. To evaluate for COVID-19 treatments that showed no benefits in subsequent large RCTs how many of their most-cited clinical studies had declared favorable results for these interventions. Methods. Scopus (last update December 23, 2021) identified articles on lopinavir-ritonavir, hydroxycholoroquine/azithromycin, remdesivir, convalescent plasma, colchicine or interferon (index interventions) that represented clinical trials and that had received >150 citations. Their conclusions were assessed and correlated with study design features. The ten most recent citations for the most-cited article on each index intervention were examined on whether they were critical to the highly-cited study. Altmetric scores were also obtained. Findings. 40 articles of clinical studies on these index interventions had received >150 citations (7 exceeded 1,000 citations). 20/40 (50%) had favorable conclusions and 4 were equivocal. Highly-cited articles with favorable conclusions were rarely RCTs while those without favorable conclusions were mostly RCTs (3/20 vs 15/20, p=0.0003). Only 1 RCT with favorable conclusions had sample size >160. Citation counts correlated strongly with Altmetric scores, in particular news items. Only 9 (15%) of 60 recent citations to the most highly-cited studies with favorable or equivocal conclusions were critical to the highly-cited study. Conclusion. Many clinical studies with favorable conclusions for largely ineffective COVID-19 treatments are uncritically heavily cited and disseminated. Early observational studies and small randomized trials may cause spurious claims of effectiveness that get perpetuated.

Inhaled corticosteroids and incident pneumonia in patients with asthma: Systematic review and meta-analysis

Acta Medica Academica ◽

10.5644/ama2006-124.141 ◽

2015 ◽

Vol 44 (2) ◽

pp. 135

Author(s):

Vikas Bansal ◽

Muhammad A. Mangi ◽

Margaret M. Johnson ◽

Emir Festic

Keyword(s):

Risk Ratio ◽

Observational Studies ◽

Randomized Trials ◽

Inhaled Corticosteroids ◽

Meta Analysis ◽

Controlled Trials ◽

Randomized Controlled ◽

Increased Risk ◽

Asthma Patients

Objectives. To systematically review all available studies on inhaled corticosteroid use and incident pneumonia in asthma patients. Methods. We performed a literature search from January 1, 1993, through August 15, 2015, using PubMed, Medline, CENTRAL, EMBASE, Scopus, ISI, Regulatory Documents, Web of Science and manufacturers’ web clinical trial registries with multiple search terms. We included studies that compared the risk of incident pneumonia among patients utilizing and not utilizing inhaled corticosteroids. We then summarized risk estimates into two random-effect meta-analyses; one including randomized controlled trials and another one including observational studies. Results. Fourteen studies were estimable; ten randomized controlled trials included 19,098 participants and four observational studies included 44,016 participants. There was no heterogeneity in randomized trials and summed risk ratio demonstrated the use of inhaled corticosteroids was protective of pneumonia; risk ratio 0.74, 95% CI 0.57to 0.95, p=0.02. On the contrary, observational studies showed summed odds ratio of 1.97; 95% CI 1.87to 2.07, p<0.0001, I²=0%, suggesting increased risk of pneumonia with use of inhaled corticosteroids in asthma patients. Conclusions: Inhaled corticosteroids are associated with decreased risk of incident pneumonia in patients with asthma based on meta-analysis of available randomized trials. Although observational studies in similar patients suggested higher risk of pneumonia, the inherent methodological limitations confer lower grade of confidence in these studies.

Enhancing Patient Centricity and Advancing Innovation in Clinical Research with Virtual Randomized Clinical Trials (vRCTs)

Diagnostics ◽

10.3390/diagnostics11020151 ◽

2021 ◽

Vol 11 (2) ◽

pp. 151

Author(s):

Raphael A. Yaakov ◽

Özgür Güler ◽

Tim Mayhugh ◽

Thomas E. Serena

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Regulatory Compliance ◽

Small Sample ◽

Controlled Trials ◽

Holistic View ◽

Health Crisis ◽

Randomized Controlled ◽

Healthcare Needs

The current public health crisis has highlighted the need to accelerate healthcare innovation. Despite unwavering levels of cooperation among academia, industry, and policy makers, it can still take years to bring a life-saving product to market. There are some obvious limitations, including lack of blinding or masking and small sample size, which render the results less applicable to the real world. Traditional randomized controlled trials (RCTs) are lengthy, expensive, and have a low success rate. There is a growing acknowledgement that the current process no longer fully meets the growing healthcare needs. Advances in technology coupled with proliferation of telehealth modalities, sensors, wearable and connected devices have paved the way for a new paradigm. Virtual randomized controlled trials (vRCTs) have the potential to drastically shorten the clinical trial cycle while maximizing patient-centricity, compliance, and recruitment. This new approach can inform clinical trials in real time and with a holistic view of a patient’s health. This paper provides an overview of virtual clinical trials, addressing critical issues, including regulatory compliance, data security, privacy, and ownership.

The effect of almond intake on lipid profile: a systematic review and meta-analysis of randomized controlled trials

Food & Function ◽

10.1039/d0fo02878a ◽

2021 ◽

Author(s):

Omid Asbaghi ◽

Vihan Moodi ◽

Amir Hadi ◽

Elham Eslampour ◽

Mina Shirinbakhshmasoleh ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Lipid Profile ◽

Meta Analysis ◽

Controlled Trials ◽

A number of clinical trials have examined the effect of almond intake on the lipid profile in recent years; however, the results remain equivocal.

Trends in randomized controlled trials in ENT: a 30-year review

The Journal of Laryngology & Otology ◽

10.1017/s0022215100138101 ◽

1997 ◽

Vol 111 (7) ◽

pp. 611-613 ◽

Cited By ~ 9

Author(s):

K. W. Ah-See ◽

N. C. Molony ◽

A. G. D. Maran

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

Gold Standard ◽

Controlled Trials ◽

Evidence Based ◽

Controlled Clinical Trials ◽

Medline Search ◽

Randomized Controlled Clinical Trials ◽

AbstractThere is a growth in the demand for clinical practice to be evidence based. Recent years have seen a rise in the number of randomized controlled clinical trials (RCTS). Such trials while acknowledged as the gold standard for evidence can be difficult to perform in surgical specialities. We have recently identified a low proportion of RCTS in the otolaryngology literature. Our aim was to identify any trend in the number of published RCTS within the ENT literature over a 30-year period and to identify which areas of our speciality lend themselves to this form of study design. A Medline search of 10 prominent journals published between 1966 and 1995 was performed. Two hundred and ninety-six RCTS were identified. Only five were published before 1980. Two hundred (71 per cent) of RCTS were in the areas of otology and rhinology. An encouraging trend is seen in RCTS within ENT literature.

Rate of adjudication of radiological progression in rheumatoid arthritis randomized controlled trials depending on preset limits of agreement: a pooled analysis from 15 randomized trials

Rheumatology ◽

10.1093/rheumatology/kes398 ◽

2013 ◽

Vol 52 (8) ◽

pp. 1404-1407 ◽

Cited By ~ 2

Author(s):

V. Navarro-Compan ◽

R. Landewe ◽

H. A. Ahmad ◽

C. G. Miller ◽

D. Xu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Randomized Trials ◽

Pooled Analysis ◽

Controlled Trials ◽

Limits Of Agreement ◽

Radiological Progression ◽

A Review of Marital Intimacy-Enhancing Interventions among Married Individuals

Global Journal of Health Science ◽

10.5539/gjhs.v8n8p74 ◽

2015 ◽

Vol 8 (8) ◽

pp. 74 ◽

Cited By ~ 4

Author(s):

Maryam Kardan-Souraki ◽

Zeinab Hamzehgardeshi ◽

Ismail Asadpour ◽

Reza Ali Mohammadpour ◽

Soghra Khani

Keyword(s):

Clinical Trials ◽

Cochrane Library ◽

Controlled Trials ◽

Main Concern ◽

Care Providers ◽

Marital Intimacy ◽

Randomized Controlled ◽

The Impact

BACKGROUND: Lack of intimacy is currently the main concern rather than main concern of the experts in psychology and counseling. It is considered as one of the most important causes for divorce and as such to improve marital intimacy a great number of interventions have been proposed in the literature. Intimacy training and counseling make the couples take effective and successful steps to increase marital intimacy. No study has reviewed the interventions promoting marital intimacy after marriage. Thus, this review study aimed to classify the articles investigating the impact of interventional programs on marital intimacy after marriage.SEARCH METHODS: In April 2015, we performed a general search in Google Scholar search engines, and then we did an advanced search the databases of Science Direct, ProQuest, SID, Magiran, Irandoc, Pubmed, Scopus, <a href="http://www.cochranelibrary.com/">Cochrane Library</a>, and Psych info; Cumulative Index to Nursing and Allied Health Literature (CINAHL). Also, lists of the references of the relevant articles were reviewed for additional citations. Using Medical Subject Headings (MESH) keywords: Intervention (Clinical Trials, Non-Randomized Controlled Trials, Randomized Controlled Trials, Education), intimacy, marital (Marriage) and selected related articles to the study objective were from 1995 to April 2015. Clinical trials that evaluated one or more behavioral interventions to improve marital intimacy were reviewed in the study.MAIN RESULTS: 39 trials met the inclusion criteria. Eleven interventions had follow-up, and 28 interventions lacked follow-up. The quality evidence for 22 interventions was low, for 15 interventions moderate, and for one intervention was considered high. Findings from studies were categorized in 11 categories as the intimacy promoting interventions in dimensions of emotional, psychological, physical, sexual, temporal, communicational, social and recreational, aesthetic, spiritual, intellectual intimacy, and total intimacy.AUTHORS’ CONCLUSIONS: Improving and promoting communication, problem solving, self-disclosure and empathic response skills and sexual education and counseling in the form of cognitive-behavioral techniques and based on religious and cultural context of each society, an effective step can be taken to enhance marital intimacy and strengthen family bonds and stability. Health care providers should consider which interventions are appropriate to the couple characteristics and their relationships.

SGLT2 inhibitors and the risk of diabetic ketoacidosis among adults with Type 2 Diabetes: A systematic review and meta-analysis

10.1101/2021.03.17.21253796 ◽

2021 ◽

Author(s):

Michael Colacci ◽

John Fralick ◽

Ayodele Odutayo ◽

Michael Fralick

Keyword(s):

Diabetic Ketoacidosis ◽

Observational Studies ◽

Randomized Trials ◽

Meta Analysis ◽

Sglt2 Inhibitor ◽

Sglt2 Inhibitors ◽

Controlled Trials ◽

Absolute Rate ◽

Importance: The risk of diabetic ketoacidosis (DKA) with sodium-glucose cotransporter-2 (SGLT2) inhibitors is unclear. Objective: To examine the risk of DKA with SGLT2 inhibitors in both observational studies and large clinical trials. Data Sources: Searches of PubMed, EMBASE and CENTRAL (inception to 15 April 2019) without language restrictions; conference proceedings; and reference lists. Study Selection: Randomized controlled trials and observational studies that quantified the rate of diabetic ketoacidosis with an SGLT2 inhibitor in comparison to another diabetes medication or placebo. Data Extraction and Synthesis: Two independent investigators abstracted study data and assessed the quality of evidence. Data were pooled using random effects models with the Hartung-Knapp-Sidik-Jonkman method. Main Outcome and Measures: Absolute event rates and hazard ratios for diabetic ketoacidosis were extracted from each study. Results: Seven randomized trials encompassing 42,375 participants and five cohort studies encompassing 318,636 participants were selected. Among the 7 randomized controlled trials, the absolute rate of DKA among patients randomized to an SGLT2 inhibitor ranged from 0.6 to 2.2 events per 1000 person years. Four randomized trials were included in the meta-analysis, and compared to placebo or comparator medication, SGLT2 inhibitors had a 2.4-fold higher risk of DKA (Relative Risk [RR] = 2.46 [95% CI, 1.16-5.21]; I2 = 0%; P = 0.54). Among the 5 observational studies, the absolute rate of DKA associated with SGLT2 inhibitor use ranged from 0.6 to 4.9 per 1000 person years and a 1.7-fold higher rate of DKA compared to another diabetes medication (RR = 1.74 [95% CI, 1.01-2.93]; I2 = 45%; P = 0.12). Conclusions and Relevance: In adults with type 2 diabetes, SGLT2 inhibitors increase the risk of DKA in both observational studies and large randomized clinical trials. Registration: CRD42019146855 Funding Source: None

Network Meta-Analysis of Different Clinical Commonly Used Drugs for the Treatment of Hypertrophic Scar and Keloid

Frontiers in Medicine ◽

10.3389/fmed.2021.691628 ◽

2021 ◽

Vol 8 ◽

Author(s):

Sha Yang ◽

Yujia J. Luo ◽

Cong Luo

Keyword(s):

Clinical Trials ◽

Topical Treatment ◽

Hypertrophic Scar ◽

Meta Analysis ◽

Treatment Strategies ◽

Controlled Trials ◽

Cochrane Central Register ◽

Randomized Controlled ◽

Silicone Gels

Background: There is no uniform treatment for pathological scars, including keloids and hypertrophic scars, in clinic currently. Previously, multiple randomized controlled trials have examined the clinical efficacy of different treatments. Nonetheless, the results are inconsistent, and many treatments have not been directly compared. This makes it difficult to conclude which approach is more favorable, in terms of efficacy and safety, for the treatment of pathological scarring. This study aimed at evaluating the efficacy of different injection and topical treatment strategies for hypertrophic scar and keloid.Methods: Relevant literature from PubMed, Medline, Embase, Scopus, the Cochrane Central Register of Controlled Trials (CCRCT), and WHO International Clinical Trials Registry Platform (WHO-ICTRP) were searched, from database inception through November 2020. Randomized clinical trials evaluating different treatment strategies of pathological scars, including triamcinolone acetonide (TAC), verapamil (VER), 5-fluorouracil (5-FU), botulinum toxin A (BTA), bleomycin (BLM), and silicone gels were included in the study.Results: The network meta-analysis included a total of 2,009 patients from 29 studies. A network meta-analysis of injection and topical treatment strategies showed that the efficacy of TAC combined with BTA was best in the treatment of pathological scars. Combination therapies of TAC with 5-FU and TAC with BTA significantly improved the clinical efficiency. However, there was no statistically significant difference between other treatment strategies. The order of efficacy predicted by the surface under the cumulative ranking (SUCRA) curve was as follows: TAC+BTA (82.2%) > TAC+5-FU (69.8%) > BTA (67.3%) > 5-FU+silicone (59.4%) > TAC+silicone (58.3%) > 5-FU (49.8%) > BLM (42.0%) > TAC (26.7%) > VER (26.2%) > silicone (18.3%). There was no publication bias revealed based on the funnel diagram.Conclusion: This study recommends intralesional injection of TAC-BTA and TAC-5-FU combined therapies. But for patients who cannot tolerate the side effects, the use of silicone gels in combination with TAC is recommended. However, these conclusions need to be further confirmed by more randomized controlled trials.

Impact of Ramadan Diurnal Intermittent Fasting on Hypoglycemic Events in Patients With Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials and Observational Studies

Frontiers in Endocrinology ◽

10.3389/fendo.2021.624423 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dana Abdelrahim ◽

MoezAlIslam E. Faris ◽

Mohamed Hassanein ◽

Ayman Z. Shakir ◽

Ayesha M. Yusuf ◽

...

Keyword(s):

Systematic Review ◽

Type 2 Diabetes ◽

Observational Studies ◽

Dietary Behaviors ◽

Controlled Trials ◽

Ramadan Fasting ◽

Randomized Controlled ◽

The Impact

Ramadan is the 9th month of the lunar calendar during which Muslims abstain from food and drink between dawn and sunset for 30 consecutive days. Ramadan fasting is observed by all healthy Muslim adults, as well many Muslims with type 2 diabetes (T2DM). Hypoglycemic events (HE) are a serious complication associated with diabetes management and are associated with increased cardiovascular disease risk. Conflicting results have been reported concerning the incidence of HE among people with T2DM observing Ramadan fasting. This review summarizes available scientific evidence on the occurrence of HE and the effects of different moderators on the incidence of HE among patients with T2DM during Ramadan. We conducted a systematic review of available observational studies and randomized controlled trials (RCTs) for patients with T2DM who fasted during Ramadan, with HE as the primary outcome. Ten databases were searched for relevant studies from inception until October 31, 2020. In total, 68 studies (35 RCTs and 33 observational studies) met the inclusion criteria. Non-sulfonylureas hypoglycemic medications showed superior effects in lowering the incidence of HE over sulfonylureas hypoglycemic medications. Variable moderators were associated with experiencing HE during Ramadan in both observational studies and RCTs, including sex, geographical location, body anthropometric indicators, season, dietary behaviors, fasting duration, time since diagnosis, and pre-fasting education. This comprehensive systematic review covered the largest number of observational and clinical studies investigating the impact of Ramadan on HE among patients with T2DM. The study highlights the significance of different moderators that influence the effect of Ramadan fasting on HE, including dietary behaviors, fasting time duration, sex, season, country, pre-fasting education, age, and time since diagnosis. The study also highlighted the impact of different hypoglycemic medications on HE and noted the superiority of non-sulfonylureas over sulfonylureas hypoglycemic medications in lowering the risk for hypoglycemia in people with T2DM during Ramadan fasting.