scholarly journals How to prove that your therapy is effective, even when it is not: a guideline

2015 ◽  
Vol 25 (5) ◽  
pp. 428-435 ◽  
Author(s):  
P. Cuijpers ◽  
I. A. Cristea

Aims.Suppose you are the developer of a new therapy for a mental health problem or you have several years of experience working with such a therapy, and you would like to prove that it is effective. Randomised trials have become the gold standard to prove that interventions are effective, and they are used by treatment guidelines and policy makers to decide whether or not to adopt, implement or fund a therapy.Methods.You would want to do such a randomised trial to get your therapy disseminated, but in reality your clinical experience already showed you that the therapy works. How could you do a trial in order to optimise the chance of finding a positive effect?Results.Methods that can help include a strong allegiance towards the therapy, anything that increases expectations and hope in participants, making use of the weak spots of randomised trials (risk of bias), small sample sizes and waiting list control groups (but not comparisons with existing interventions). And if all that fails one can always not publish the outcomes and wait for positive trials.Conclusions.Several methods are available to help you show that your therapy is effective, even when it is not.

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 75
Author(s):  
Álvaro Navarro-Castilla ◽  
Mario Garrido ◽  
Hadas Hawlena ◽  
Isabel Barja

The study of the endocrine status can be useful to understand wildlife responses to the changing environment. Here, we validated an enzyme immunoassay (EIA) to non-invasively monitor adrenocortical activity by measuring fecal corticosterone metabolites (FCM) in three sympatric gerbil species (Gerbillus andersoni, G. gerbillus and G. pyramidum) from the Northwestern Negev Desert’s sands (Israel). Animals included into treatment groups were injected with adrenocorticotropic hormone (ACTH) to stimulate adrenocortical activity, while control groups received a saline solution. Feces were collected at different intervals and FCM were quantified by an EIA. Basal FCM levels were similar in the three species. The ACTH effect was evidenced, but the time of FCM peak concentrations appearance differed between the species (6–24 h post-injection). Furthermore, FCM peak values were observed sooner in G. andersoni females than in males (6 h and 18 h post-injection, respectively). G. andersoni and G. gerbillus males in control groups also increased FCM levels (18 h and 48 h post-injection, respectively). Despite the small sample sizes, our results confirmed the EIA suitability for analyzing FCM in these species as a reliable indicator of the adrenocortical activity. This study also revealed that close species, and individuals within a species, can respond differently to the same stressor.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M P Rimmer ◽  
N Black ◽  
S Keay ◽  
S Quenby ◽  
B. H.A Wattar

Abstract Study question What is the effectiveness of IV Intralipid (IVI) in improving pregnancy rates in women undergoing IVF with history of Recurrent implantation failure (RIF) to improve reproductive outcomes. Summary answer The evidence to support the use of IVI at the time of embryo transfer in women with RIF is limited. More RCTs are needed. What is known already: Optimising the implantation process following embryo transfer remains a clinical challenge with 10% of couples undergoing IVF affected by (RIF). Immunotherapy could help to optimise endometrial receptivity and increase the chances for successful conception in women with history of RIF. Intra-venous Intralipid (IVI), a fat-based emulsion of soybean oil, glycerine, phospholipids, egg, and polyunsaturated fatty acids, has been evaluated in several trials as a potential intervention to downregulate the uNK cells and macrophages as well as inhibit the pro-inflammatory mediators including T1 helper cells. Evidence synthesis is needed to evaluate the effectiveness of this intervention. Study design, size, duration We performed this systematic review using a prospectively registered protocol (CRD42019148517) and reported in accordance with the PRISMA guidelines. Participants/materials, setting, methods: We searched MEDLINE, EMBASE and CENTRAL for any randomised trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta-analysed data using a random effect model and reported on dichotomous outcomes using risk ratio (RR) and 95% confidence interval (CI). Main results and the role of chance We included five randomised trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, RR 1.55, 95%CI 1.16–2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95%CI 1.42–2.35, I2 0%) post treatment compared to no intervention. Limitations, reasons for caution Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics. Wider implications of the findings: Our meta-analysis offers an overview on the value of IVI to help women affected by RIF. Given the limitations and the quality of included trials, adopting the use of IVI a-la-carte to couples undergoing IVF remains immature. IVI should not be offered until larger RCTs demonstrate a persistent benefit. Trial registration number CRD42019148517


2015 ◽  
Vol 10 (1) ◽  
pp. 95
Author(s):  
Elizabeth Margaret Stovold

A Review of: Perrier, L., Farrell, A., Ayala, A. P., Lightfoot, D., Kenny, T., Aaronson, E., . . . Weiss, A. ( 2014). Effects of librarian-provided services in healthcare settings: A systematic review. Journal of the American Medical Informatics Association, 21(6), 1118-1124. http://dx.doi.org/10.1136/amiajnl-2014-002825 Abstract Objective – To assess the effects of librarian-provided services, in any healthcare setting, on outcomes important to patients, healthcare providers, and researchers. Design – Systematic review and narrative synthesis. Setting – MEDLINE, CINAHL, ERIC, LISA, and CENTRAL databases; library-related websites, conference proceedings, and reference lists of included studies. Subjects – Twenty-five studies identified through a systematic literature search. Methods – In consultation with the review team, a librarian designed a search to be run in MEDLINE that was peer-reviewed against a published checklist. The team then conducted searches in the five identified databases, adapting the search as appropriate for each database. Authors also checked the websites of library and evidence based healthcare organisations, along with abstracts of relevant conference proceedings, to supplement the electronic search. Two authors screened the literature search results for eligible studies, and reached agreement by consensus. Studies of any librarian-delivered service in a healthcare setting, directed at either patients, clinicians of any type, researchers, or students, along with studies reporting outcomes relevant to clinicians, patients, or researchers, were eligible for inclusion. The authors assessed results initially on the titles and abstracts, and then on the full-text of potentially relevant reports. The data from included studies were then extracted into a piloted data extraction form, and each study was assessed for quality using the Cochrane EPOC risk of bias tool or the Newcastle-Ottawa scale. The results were synthesised narratively. Main Results – The searches retrieved a total of 25 studies that met the inclusion criteria, comprised of 22 primary papers and 3 companion reports. Authors identified 12 randomised trials, 4 controlled before-and-after studies, 3 cohorts, 2 non-randomised trials, and 1 case-control study. They identified three main categories of intervention: librarians teaching search skills; providing literature searching as a service; and a combination of the teaching and provision of search services. The interventions were delivered to a mix of trainees, clinicians, and students. None of the studies examined services delivered directly to patients or to researchers. The quality assessment found most of the studies had a mid- to high-risk of bias due to factors such as lack of random sequence generation, a lack of validated tools for data collection, or a lack of statistical analysis included in the study. Two studies measured patient relevant outcomes and reported that searches provided by librarians to clinicians had a positive impact on the patient’s length of stay in hospital. Five studies examined the effect of librarian provided services on outcomes important to clinicians, such as whether a literature search influenced a clinical decision. There was a trend towards a positive effect, although two studies found no significant difference. The majority of studies investigated the impact of training delivered to trainees and students on their literature search skills. Twelve of these studies found a positive effect of training on the recipients’ search skills, while three found no difference. The secondary outcomes considered by this review were satisfaction with the service (8 studies), relevance of the answers provided by librarians (2), and cost (3). The majority reported good satisfaction, and relevance. A cost benefit was found in 2 of 3 studies that reported this outcome. Conclusion – Authors report a positive effect of training on the literature search skills of trainees and students, and identified a benefit in the small number of studies that examined librarian services to clinicians. Future studies should use validated data collection tools, and further research should be conducted in the area of services provided to clinicians. Research is needed on the effect of librarian-provided services to patients and researchers as no studies meeting the inclusion criteria examining these two groups were identified by the literature search.


2021 ◽  
Author(s):  
Metin Bulus

A recent systematic review of experimental studies conducted in Turkey between 2010 and 2020 reported that small sample sizes had been a significant drawback (Bulus and Koyuncu, 2021). A small chunk of the studies were small-scale true experiments (subjects randomized into the treatment and control groups). The remaining studies consisted of quasi-experiments (subjects in treatment and control groups were matched on pretest or other covariates) and weak experiments (neither randomized nor matched but had the control group). They had an average sample size below 70 for different domains and outcomes. These small sample sizes imply a strong (and perhaps erroneous) assumption about the minimum relevant effect size (MRES) of intervention before an experiment is conducted; that is, a standardized intervention effect of Cohen’s d < 0.50 is not relevant to education policy or practice. Thus, an introduction to sample size determination for pretest-posttest simple experimental designs is warranted. This study describes nuts and bolts of sample size determination, derives expressions for optimal design under differential cost per treatment and control units, provide convenient tables to guide sample size decisions for MRES values between 0.20 ≤ Cohen’s d ≤ 0.50, and describe the relevant software along with illustrations.


2017 ◽  
Vol 42 (1) ◽  
pp. 105-115 ◽  
Author(s):  
Shannon K. Bennetts ◽  
Fiona K. Mensah ◽  
Elizabeth M. Westrupp ◽  
Naomi J. Hackworth ◽  
Jan M. Nicholson ◽  
...  

THE QUALITY AND ACCURACY OF research findings relies on the use of appropriate and sensitive research methods. To date, few studies have directly compared quantitative measurement methods in the early childhood field and the extent to which parent-reported and directly-measured behaviours agree is unclear. Existing studies are hampered by small sample sizes and the use of statistical techniques which quantify the magnitude of association between measures (e.g. correlations), but not agreement. Here we review the limitations of existing method comparisons and suggest how alternative statistical approaches such as the Bland-Altman Method and ordinary least products regression can be readily applied in the early childhood context. Understanding agreement (and disagreement) between measurement methods has potential to reduce research costs and improve data quality, with important implications for researchers, clinicians and policy-makers.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Long Zhang ◽  
Charles Layne ◽  
Thomas Lowder ◽  
Jian Liu

As a popular exercise form, Tai Chi (TC) has been investigated to determine its contributions to an active and healthy lifestyle. There are an increasing number of researchers who focus on exploring the potential physiological and psychological benefits of TC but only a few systematic reviews of these benefits to a variety of populations. The purpose of this paper is to comprehensively evaluate the reported psychological benefits associated with practicing TC. Although many investigators have reported possible psychological benefits of TC for children, young adults, older healthy adults, and for a variety of patient populations, many of the reports suffer one or more methodological flaws. These flaws include inadequate study design, including lack of control groups, small sample sizes, unsophisticated statistical techniques, or publication without rigorous peer review. After reviewing the results of the existing literature regarding the potential psychological benefits of TC, we recommend that future investigations be conducted with additional adherence to the traditional scientific process.


2021 ◽  
Author(s):  
Elaine Finucane ◽  
Ann O’Brien ◽  
Shaun Treweek ◽  
John Newell ◽  
Kishor Das ◽  
...  

Abstract BackgroundRandomised trials are considered the gold standard in providing robust evidence on the effectiveness of interventions. However, there are relatively few initiatives to help increase public understanding of what randomised trials are and why they are important. This limits the overall acceptance of and public participation in clinical trials. The People’s Trial aims to help the public learn about randomised trials, to understand why they matter, and to be better equipped to think critically about health claims. MethodsUsing a reflexive approach, we describe the processes of development, conduct and dissemination of The People’s Trial. ResultsOver 3000 members of the public, from 72 countries, participated in The People’s Trial. Through a series of online surveys, the public chose the question The People’s Trial would try to answer and decided the components of the trial question. In December 2019, 991 participants were recruited to a trial to answer the question identified and prioritised by the public, i.e., ‘Does reading a book in bed make a difference to sleep in comparison to not reading a book in bed?’ We called this trial The Reading Trial.We report processes of The People’s Trial in seven phases, paralleling the steps of a randomised trial, i.e., question identification and prioritisation, recruitment, randomisation, trial conduct, data analysis, and sharing of findings. We describe the decisions we made, the processes we used, the challenges we encountered, and the lessons we learned. ConclusionThe People’s trial engaged members of the public successfully in the design, conduct, and dissemination of a randomised trial demonstrating the potential for such initiatives to help the public learn about randomised trials, to understand why they matter, and to be better equipped to think critically about health claims. Trial Registration The Reading Trial was registered 4th December 2019 on ClinicalTrials.gov, ID: NCT04185818.


2021 ◽  
Vol 11 (10) ◽  
pp. 4457
Author(s):  
Lin Ang ◽  
Eunhye Song ◽  
Hye Won Lee ◽  
Myeong Soo Lee

This review aims to evaluate the effectiveness of acupressure as a treatment method for osteoarthritis. Fourteen electronic databases were searched from the date of inception until 16 March 2021, for eligible studies. Studies comparing acupressure with sham acupuncture, no intervention or conventional intervention were eligible for inclusion. The risk of bias of the included studies was assessed using the Cochrane Collaboration’s Risk of Bias Assessment tool Version 2.0. A total of eight trials were included in this review, focusing on the seven trials investigating knee osteoarthritis. The risk of bias is judged as low in only two trials and concerning in the remaining six trials. The meta-analysis showed that acupressure has equivalent effects in reducing pain (p = 0.12), relieving stiffness (p = 0.38), and improving physical function (p = 0.12), as compared to sham acupressure. Pooled results also showed similar results where acupressure has an equivalent effect in reducing pain (p = 0.09), and relieving stiffness (p = 0.68), but showed a favorable effect in improving physical function of joints (MD –6.30, CI 95%: −11.69 to −0.92, p = 0.02), as compared to no intervention. For acupressure complementing conventional intervention, pooled results showed superior effects for easing pain compared to conventional intervention alone (MD −3.72, 95% CI: −4.84 to −2.61, p < 0.00001). Overall, the studies included in this review have concerning quality and suffer from small sample sizes, and the findings of this review should be interpreted with caution. More clinical trials with proper methodology are needed to confirm the effectiveness of acupressure for osteoarthritis.


F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 86 ◽  
Author(s):  
Heidi R Gardner ◽  
Loai Albarquoni ◽  
Adel El Feky ◽  
Katie Gillies ◽  
Shaun Treweek

Background: Recruitment to trials can be challenging. Currently, non-randomised evaluations of trial recruitment interventions are rejected due to poor methodological quality, but systematic assessment of this substantial body of work may inform trialists’ decision-making about recruitment methods. Our objective was to quantify the effects of strategies to improve participant recruitment to randomised trials evaluated using non-randomised study designs. Methods: We searched relevant databases for non-randomised studies that included two or more interventions evaluating recruitment to trials. Two reviewers screened abstracts and full texts for eligible studies, then extracted data on: recruitment intervention, setting, participant characteristics, number of participants in intervention and comparator groups. The ROBINS-I tool was used to assess risk of bias. The primary outcome was the number of recruits to a trial. Results: We identified 92 studies for inclusion; 90 studies aimed to improve the recruitment of participants, one aimed to improve the recruitment of GP practices, and one aimed to improve recruitment of GPs. Of the 92 included studies, 20 were at high risk of bias due to confounding; the remaining 72 were at high risk of bias due to confounding and at least one other category of the ROBINS-I tool. The 20 studies at least risk of bias were synthesised narratively based on seven broad categories; Face to face recruitment initiatives, postal invitations and responses, language adaptations, randomisation methods, trial awareness strategies aimed at the recruitee, trial awareness strategies aimed at the recruiter, and use of networks and databases. The utility of included studies is substantially limited due to small sample sizes, inadequate reporting, and a lack of coordination around deciding what to evaluate and how. Conclusions: Careful thought around planning, conduct, and reporting of non-randomised evaluations of recruitment interventions is required to prevent future non-randomised studies contributing to research waste. Registration: PROSPERO CRD42016037718


Parasitology ◽  
2010 ◽  
Vol 138 (4) ◽  
pp. 405-425 ◽  
Author(s):  
G. SCHÖNIAN ◽  
K. KUHLS ◽  
I. L. MAURICIO

SUMMARYMolecular approaches are being used increasingly for epidemiological studies of visceral and cutaneous leishmaniases. Several molecular markers resolving genetic differences betweenLeishmaniaparasites at species and strain levels have been developed to address key epidemiological and population genetic questions. The current gold standard, multilocus enzyme typing (MLEE), needs cultured parasites and lacks discriminatory power. PCR assays identifying species directly with clinical samples have proven useful in numerous field studies. Multilocus sequence typing (MLST) is potentially the most powerful phylogenetic approach and will, most probably, replace MLEE in the future. Multilocus microsatellite typing (MLMT) is able to discriminate below the zymodeme level and seems to be the best candidate for becoming the gold standard for distinction of strains. Population genetic studies by MLMT revealed geographical and hierarchic population structure inL. tropica, L. majorand theL. donovanicomplex. The existence of hybrids and gene flow betweenLeishmaniapopulations suggests that sexual recombination is more frequent than previously thought. However, typing and analytical tools need to be further improved. Accessible databases should be created and sustained for integrating data obtained by different researchers. This would allow for global analyses and help to avoid biases in analyses due to small sample sizes.


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