Meta-Analysis: Lactobacillus Containing Quadruple Therapy Versus Standard Triple First-Line Therapy for Helicobacter pylori Eradication

Background:  Recent evidence showed that Lactobacilli could exert an inhibitory effect on Helicobacter pylori both in vitro and in vivo models. To systematically evaluate whether adding Lactobacilli to H. pylori eradication regimens could improve eradication rates and reduce side effects during anti- H. pylori treatment.
Materials and Methods:  Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing Lactobacilli supplementation to placebo or no treatment during anti- H. pylori regimens. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis analysis was also performed.
Results:  We identified eight randomized trials (n = 1372). Pooled H. pylori eradication rates were 82.26% (95% CI = 78.01–86.51%) and 76.97% (95% CI = 73.11–80.83%) for patients with or without Lactobacilli by intention-to-treat analysis, respectively, the odds ratio (OR) was 1.78 (95% CI = 1.21–2.62). The occurrence of total side effects had no significant difference and were 30.84% (95% CI = 24.82–36.86%) and 42.24% (95% CI = 35.89%–48.59%) for two groups, the summary OR was 0.49 (95% CI = 0.24–1.02); However, Lactobacilli supplementation group had lower occurrence of diarrhoea, bloating and taste disturbance.
Conclusions:  Our review suggests that supplementation with Lactobacilli could be effective in increasing eradication rates of anti- H. pylori therapy for first-treated patients. Furthermore, Lactobacilli showed a positive impact on some H. pylori therapy-related side effects.     

Meta-Analysis: The Effect of Supplementation with Lactoferrin on Eradication Rates and Adverse Events During Helicobacter pylori Eradication Therapy

Background: Recent evidence shown that lactoferrin could exert an antimicrobial effect against Helicobacter pylori both in vitro and in vivo models. To systematically evaluate whether adding lactoferrin to H. pylori eradication regimens could improve eradication rates and reduce side-effects during anti- H. pylori treatment.
Materials and Methods:  Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing lactoferrin supplementation to placebo or no treatment during anti- H. pylori regimens. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis/Sensitivity analysis was also performed.
Results: We identified nine randomized trials (n = 1343). Pooled H. pylori eradication rates were 86.57% (95% confidence interval (CI) = 83.99–89.15%) and 74.44% (95% CI = 71.14–77.74%) for patients with or without lactoferrin by intention-to-treat analysis, respectively, the odds ratio (OR) was 2.26 (95% CI = 1.70–3.00); the occurrence of total side-effects was 9.05% (95% CI = 6.83–11.27%) and 16.28% (95% CI = 13.43%–19.13%) for groups with or without lactoferrin, especially for nausea, the summary OR was 0.15 (95% CI = 0.04–0.54).
Conclusions: Our review suggests that supplementation with lactoferrin could be effective in increasing eradication rates of anti- H. pylori therapy, and could be considered helpful for patients with eradication failure. Furthermore, lactoferrin shows a positive impact on H. pylori therapy-related side-effects.     

LTA 252GG and GA Genotypes are Associated with Diffuse-Type Noncardia Gastric Cancer Risk in the Japanese Population

Background:  There are limited numbers of reports on the association of lymphotoxin-alpha ( LTA ) genotypes with gastric cancer.
Methods:  A nested case–control study was carried out in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years) and blood cells. Enrolled were 287 cases with noncardia gastric cancer of diffuse and intestinal types and three controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and counter-matched on radiation dose.
Results:  LTA 252GG and GA genotypes were associated with the prevalence of Helicobacter pylori IgG seropositivity and higher antibody titer against H. pylori cytotoxin-associated gene A (CagA) protein in controls and they were an independent risk factor for noncardia gastric cancer of diffuse type (RR = 2.8 (95% CI: 1.3–6.3), p  =   .01, and RR = 2.7 (95% CI: 1.5–4.8), p  <   .001), but not for intestinal type, after adjusting for H. pylori IgG seropositivity, CagA antibody titers, chronic atrophic gastritis, smoking, and radiation dose. Cessation of smoking (RR = 0.4 (95% CI: 0.2–0.7), p  <   .001) and never smoking (RR = 0.4 (95% CI: 0.3–0.6), p  <   .001) were both protective for future noncardia gastric cancer. Radiation dose was associated with noncardia gastric cancer in subjects with both the LTA 252G -allele and never smoking/quit smoking histories (RR = 3.8 (95% CI: 1.7–5.9), p  =   .009).
Conclusion:  The LTA 252 genotype is associated with noncardia gastric cancer of diffuse type in Japan and interacted with radiation dose.     

Bismuth-Containing Quadruple Therapy as Second-Line Treatment for Helicobacter pylori Infection: Effect of Treatment Duration and Antibiotic Resistance on the Eradication Rate in Korea

Background:  The eradication rate of first-line Helicobacter pylori treatment is only 70–85% and has been decreasing due to the increase in antibiotic resistance. The aim of this study was to evaluate the efficacy of bismuth-containing quadruple therapy as second-line treatment for H. pylori infection based on treatment duration.
Methods:  We prospectively enrolled 227 patients that were found to have persistent H. pylori infection after first-line proton-pump inhibitor-clarithromycin-amoxicillin triple therapy. Patients were randomized to 1-week (112 patients) and 2-week (115 patients) quadruple therapy with tripotassium dicitrate bismuthate 300 mg q.i.d., meteronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. and esomeprazole 20 mg b.i.d. The eradication rate, drug compliance, and adverse events were compared based on treatment duration.
Results:  The eradication rates were 72/112 (64.3%, 95% CI: 0.504–0.830) and 71/92 (77.2%, 0.440–0.749) with 1-week group, and 95/115 (82.6%, 1.165–2.449) an 88/94 (93.6%, 1.213–5.113) with 2-week group by intention-to-treat therapy ( p  = .002) and per-protocol analysis ( p  = .001), respectively. The adverse events increased as the treatment durations increased from 7 to 14 days (20.0 and 42.5%, respectively, p  < .001). However, there was no significant difference in the patient compliance or the rate of major adverse events between the 1- and 2-week groups (6.3 and 12.5%, respectively, p  = .133).
Conclusion:  Two-week bismuth-containing quadruple therapy was more effective than the 1-week treatment, and should be considered for second-line treatment in Korea.     

Clinical Significance of IgG Antibody Titer against Helicobacter pylori

Background: We clarified the clinical significance of measurement of IgG antibody titers against Helicobacter pylori using data from a nested case–control study from a large-scale cohort study in Japan.
Method: Participants included 36,745 subjects from the Japan Health Center-based Prospective Study who responded to the baseline questionnaire and provided a blood sample. Subjects were aged 40–69 years and were followed over 15 years after initial sampling. Controls were matched to 511 gastric cancer patients. Plasma surface antigen (Hp)-IgG titer was measured using ELISA, and mucosal atrophy was determined by measuring pepsinogen I and II levels.
Results: Seropositive subjects with low Hp-IgG titer and mucosal atrophy showed a higher risk for gastric cancer than high-titer subjects. Odds ratio (OR) referred to cases with true negative IgG titers and no mucosal atrophy. In moderately atrophic subjects, the low titer OR was 19.0, with a 95% confidence interval (CI) of 7.7–46.9, and 12.5 for high titer, with a 95% CI of 5.2–30.0. In severely atrophic subjects, the low titer OR was almost double that of high-titer subjects (OR = 30.2, 95% CI = 12.4–73.7 and OR = 15.9, 95% CI = 6.3–40.3, respectively). These associations were observed more frequently for differentiated than undifferentiated gastric cancer.
Conclusion: Combination assay with Hp-IgG titer and pepsinogens may help identify groups at high risk for gastric cancer. Subjects with low Hp-IgG titer and mucosal atrophy were at extremely high risk for gastric cancer, particularly differentiated cancer. Subjects with this background may require ongoing observation and periodic endoscopic examination for early cancer detection.     

Predicting treatment effect from surrogate endpoints and historical trials: an extrapolation involving probabilities of a binary outcome or survival to a specific time

Using multiple historical trials with surrogate and true endpoints, we consider various models to predict the effect of treatment on a true endpoint in a target trial in which only a surrogate endpoint is observed. This predicted result is computed using (1) a prediction model (mixture, linear, or principal stratification) estimated from historical trials and the surrogate endpoint of the target trial and (2) a random extrapolation error estimated from successively leaving out each trial among the historical trials. The method applies to either binary outcomes or survival to a particular time that is computed from censored survival data. We compute a 95% confidence interval for the predicted result and validate its coverage using simulation. To summarize the additional uncertainty from using a predicted instead of true result for the estimated treatment effect, we compute its multiplier of standard error. Software is available for download.     

Outcomes in registered, ongoing randomized controlled trials of patient education

Background

With the increasing prevalence of chronic noncommunicable diseases, patient education is becoming important to strengthen disease prevention and control. We aimed to systematically determine the extent to which registered, ongoing randomized controlled trials (RCTs) evaluated an educational intervention focus on patient-important outcomes (i.e., outcomes measuring patient health status and quality of life).

Methods

On May 6, 2009, we searched for all ongoing RCTs registered in the World Health Organization International Clinical Trials Registry platform. We used a standardized data extraction form to collect data and determined whether the outcomes assessed were 1) patient-important outcomes such as clinical events, functional status, pain, or quality of life or 2) surrogate outcomes, such as biological outcome, treatment adherence, or patient knowledge.

Principal Findings

We selected 268 of the 642 potentially eligible studies and assessed a random sample of 150. Patient-important outcomes represented 54% (178 of 333) of all primary outcomes and 46% (286 of 623) of all secondary outcomes. Overall, 69% of trials (104 of 150) used at least one patient-important outcome as a primary outcome and 66% (99 of 150) as a secondary outcome. Finally, for 31% of trials (46 of 150), primary outcomes were only surrogate outcomes. The results varied by medical area. In neuropsychiatric disorders, patient important outcomes represented 84% (51 of 61) of primary outcomes, as compared with 54% (32 of 59) in malignant neoplasm and 18% (4 of 22) in diabetes mellitus trials.In addition, only 35% assessed the long-term impact of interventions (i.e., >6 months).

Conclusions

There is a need to improve the relevance of outcomes and to assess the long term impact of educational interventions in RCTs.     

Carotid intimal-media thickness as a surrogate for cardiovascular disease events in trials of HMG-CoA reductase inhibitors

BACKGROUND: Surrogate measures for cardiovascular disease events have the potential to increase greatly the efficiency of clinical trials. A leading candidate for such a surrogate is the progression of intima-media thickness (IMT) of the carotid artery; much experience has been gained with this endpoint in trials of HMG-CoA reductase inhibitors (statins). METHODS AND RESULTS: We examine two separate systems of criteria that have been proposed to define surrogate endpoints, based on clinical and statistical arguments. We use published results and a formal meta-analysis to evaluate whether progression of carotid IMT meets these criteria for HMG-CoA reductase inhibitors (statins).IMT meets clinical-based criteria to serve as a surrogate endpoint for cardiovascular events in statin trials, based on relative efficiency, linkage to endpoints, and congruency of effects. Results from a meta-analysis and post-trial follow-up from a single published study suggest that IMT meets established statistical criteria by accounting for intervention effects in regression models. CONCLUSION: Carotid IMT progression meets accepted definitions of a surrogate for cardiovascular disease endpoints in statin trials. This does not, however, establish that it may serve universally as a surrogate marker in trials of other agents.     

Inhibition of Helicobacter pylori Infection in Humans by Lactobacillus reuteri ATCC 55730 and Effect on Eradication Therapy: A Pilot Study

Background:  Several studies report an inhibitory effect of probiotics on Helicobacter pylori .
Aim:  To test whether Lactobacillus reuteri ATCC 55730 reduces H. pylori intragastric load in vivo, decreases dyspeptic symptoms, and affects eradication rates after conventional treatment.
Materials and Methods:  In a double-blind placebo-controlled study, 40 H. pylori -positive subjects were given L. reuteri once a day for 4 weeks or placebo. All underwent upper endoscopy, ¹³C-urea breath test, and H. pylori stool antigen determination at entry and ¹³C-urea breath test and H. pylori stool antigen (used as both qualitative and semiquantitative markers) after 4 weeks of treatment. Sequential treatment was administered subsequently to all.
Results:  In vivo, L. reuteri reduces H. pylori load as semiquantitatively assessed by both ¹³C-urea breath test δ -value and H. pylori stool antigen quantification after 4 weeks of treatment ( p <  .05). No change was shown in patients receiving placebo. L. reuteri administration was followed by a significant decrease in the Gastrointestinal Symptom Rating Scale as compared to pretreatment value ( p <  .05) that was not present in those receiving placebo ( p =  not significant). No difference in eradication rates was observed.
Conclusions:  L. reuteri effectively suppresses H. pylori infection in humans and decreases the occurrence of dyspeptic symptoms. Nevertheless, it does not seem to affect antibiotic therapy outcome.     

Acceptance and Perception of Nigerian Patients to Medical Photography

The aim of the study was to determine the acceptance and perception of Nigerian patients to medical photography. A self‐administered questionnaire was distributed among Nigerian patients attending oral and maxillofacial surgery and plastic surgery clinics of 3 tertiary health institutions. Information requested included patients' opinion about consent process, capturing equipment, distribution and accessibility of medical photographs. The use of non‐identifiable medical photographs was more acceptable than identifiable to respondents for all purposes (P = 0.003). Most respondents were favourably disposed to photographs being taken for inclusion in the case note, but opposed to identifiable photographs being used for other purposes most especially in medical websites and medical journals. Female respondents preferred non‐identifiable medical photographs to identifiable ones (P = 0.001). Most respondents (78%) indicated that their consent be sought for each of the outline needs for medical photography. Half of the respondents indicated that identifiable photographs may have a negative effect on their persons; and the most commonly mentioned effects were social stigmatization, bad publicity and emotional/psychological effects. Most of the respondents preferred the use of hospital‐owned camera to personal camera/personal camera‐phone for their medical photographs. Most respondents (67.8%) indicated that they would like to be informed about the use of their photographs on every occasion, and 74% indicated that they would like to be informed of the specific journal in which their medical photographs are to be published. In conclusion, non‐identifiable rather than identifiable medical photography is acceptable to most patients in the studied Nigerian environment. The use of personal camera/personal camera‐phone should be discouraged as its acceptance by respondents is very low. Judicious use of medical photography is therefore advocated to avoid breach of principle of privacy and confidentiality in medical practice.     

Putting placebo‐controlled trials in developing countries to the interpersonal justifiability test

This paper considers the ethics of placebo‐controlled trials in developing countries, where a treatment already exists but is not available due to the low local standard of care. Such trials would not be permitted in more developed nations where a higher standard of care is available. I argue that there are moral intuitions against such trials, but a further intuition that if the trials were aimed at producing treatment options for the developing world, that would be more permissible than if the trials were designed with the benefit of rich world people in mind. An approach based upon GA Cohen's work on interpersonal justifiability is suggested to allow us to explain these intuitions. Cohen's framework shows that these trials are ethically problematic because the inequality in healthcare provision between developing and developed nations that allows them to take place is at least partly the pharmaceutical corporations’ fault. Following Cohen's argument, this means the trials are non‐comprehensively justified. This allows for a more complete explanation of our intuitions than to consider such trials as cases of exploitation, because intuitions on the ethicacy of research can vary even when the exploitation relation remains the same. It is then established that there is good empirical evidence to believe that pharmaceutical corporations do fail the interpersonal justifiability test. The policy implications of this judgement are then considered, and it is suggested that the framework might be equally applicable to examining the permissibility of research conducted on vulnerable people within more developed nations.     

Registration of noncommercial randomised clinical trials: the feasibility of using trial registries to monitor the number of trials

ABSTRACT: BACKGROUND: A 2003 survey suggested the number of noncommercial trials in the UK was declining. Formation of the NIHR in 2006 and increased research spending by the Department of Health may have increased the number of noncommercial trials but no data are available. METHODS: Available data on UK noncommercial trials were obtained from the two relevant registries: ISRCTN register for the UK, and US ClinicalTrials.gov. Data on each trial were sorted by start year, and compared with the : 2003 survey, and UKCRN portfolio database from 2007. RESULTS: The number of UK noncommercial trials registered rose from 25 in 1990 to 188 in 1999, peaked at 533 in 2003, and fell back to 334 in 2009. Total trials registered was similar to but slightly above those in the 2003 survey up to 1998, then rose sharply to 2003 before falling to 2007. From 2007 to 2009 the number registered to start each year was similar to but slightly above the UKCRN database. Less than 10% of UK noncommercial trials registered with ClinGov for most years before 2005, but this rose to 35% by 2009. CONCLUSIONS: For the periods of overlap, trial registration data provide fairly similar totals to other sources on the number of noncommercial trials starting each year. The rise and fall in the number of trials registered between 1999 and 2007 was due to those registered in the ISRCTN database as funded by NHS Trusts. After 2007, the number of trials registered as funded by NHS Trusts has fallen in the ISRCTN register but these trials may have migrated to the US ClinGov register. The total number of noncommercial trial starts, excluding those funded by NHS Trusts, has been upward since around 2002. By 2009 the two main funders were NIHR and charities. Feasibility of using registration data to monitor the number of noncommercial trials has been demonstrated but is complicated by the use of two registers and difficulties in accessing the data. We recommend an annual report on the number of noncommercial trials registering each year.     

Helicobacter pylori cagA Gene Polymorphism Affects the Total Antioxidant Capacity of Human Saliva

Background:  We aimed to evaluate the total antioxidant capacity (TAC) of saliva in healthy Helicobacter pylori -positive and negative saliva individuals.
Materials and Methods:  A total of 102 human saliva samples were checked for the presence of H. pylori DNA ( ureA and cagA gene fragments).
TAC of saliva was estimated by ABTS radical cation (ABTS^{• +} ) decolorization assay.
Results:  PCR analysis revealed that 36 subjects were ureA-/cagA- , 24 were ureA+/cagA- and 42 were ureA+/cagA+ . Smoking habits had no evident effect on H. pylori infection.
We found that TAC of the ureA-/cagA- material, after 10 seconds reaction reflecting fast-reacting antioxidants, was significantly higher than of ureA+/cagA- and ureA+/cagA+ samples (p < .01 and p < .001, respectively). Similar results were obtained for reaction time of 3 minutes measuring slow-reacting antioxidants (p < .001). We also estimated ureA+/cagA- and ureA+/cagA+ samples alone and reported a statistically significant decrease in the TAC_3min value of ureA+/cagA+ compared with ureA+/cagA- samples (p < .05).
Conclusions:  Our data demonstrated that altered redox equilibrium may be associated with more frequent occurrence of H. pylori in the saliva samples.     

FAIR TRADE INTERNATIONAL SURROGACY

Since the development of assisted reproductive technologies, infertile individuals have crossed borders to obtain treatments unavailable or unaffordable in their own country. Recent media coverage has focused on the outsourcing of surrogacy to developing countries, where the cost for surrogacy is significantly less than the equivalent cost in a more developed country. This paper discusses the ethical arguments against international surrogacy. The major opposition viewpoints can be broadly divided into arguments about welfare, commodification and exploitation.
It is argued that the only valid objection to international surrogacy is that surrogate mothers may be exploited by being given too little compensation. However, the possibility of exploitation is a weak argument for prohibition, as employment alternatives for potential surrogate mothers may be more exploitative or more harmful than surrogacy. It is concluded that international surrogacy must be regulated, and the proposed regulatory mechanism is termed Fair Trade Surrogacy. The guidelines of Fair Trade Surrogacy focus on minimizing potential harms to all parties and ensuring fair compensation for surrogate mothers.     

Nonregistration,discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis

BackgroundWe previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs.Methods and findingsWe included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment.Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%).The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations.ConclusionsWe have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research.

Benjamin Speich and colleagues investigate whether rates of trial completion and publication have increased over the past decade, the extent to which non-published trials can be identified in registries, and the association between reporting quality of protocols and premature discontinuation or non-publication of trials.     

The quality of registration of clinical trials

Background

Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials.

Methods and Findings

A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame.

Conclusions

Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records.     

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology

Background

Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals.

Methods

Eligible RCTs were published in JCCP in 2013–2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration.

Results

Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709).

Conclusions

The quality of published outcome analysis definitions and trial registrations in JCCP is suboptimal. Greater attention to proper trial registration and outcome analysis definition in published reports is needed.     

Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions

BackgroundA large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of “positive” results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified.MethodsCINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses.Results108 (87%) of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases.ConclusionsThe proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice.