Pregnancies with 'double-positive' multiple marker screening results: a population-based study in Ontario, Canada.

BACKGROUND: Multiple marker screening is offered to pregnant individuals in many jurisdictions to screen for trisomies 21 and 18. On occasion, the result is 'double-positive'-a screening result that is unexpectedly positive for both aneuploidies. Although this occurs rarely, the paucity of available evidence about the outcomes of these pregnancies hinders patient counselling. This study aimed to investigate the association of double-positive results with preterm birth and other adverse perinatal outcomes. METHODS: We conducted a population-based retrospective cohort study of pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, using province-wide perinatal registry data in Ontario, Canada. Pregnancies with double-positive screening results where trisomies 21 and 18 were ruled-out were compared to pregnancies with screen negative results for both aneuploidies. We used modified Poisson regression models with robust variance estimation to examine the association of double positive results with preterm birth and secondary outcomes. RESULTS: From 429 540 pregnancies with multiple marker screening, 863 (0.2%) had a double-positive result; trisomies 21 and 18 were ruled out in 374 pregnancies, 203 of which resulted in a live birth. Among the pregnancies in the double-positive group resulting in a live birth, the risk of preterm birth was increased compared to pregnancies with a screen negative result: adjusted risk ratio (aRR) 2.6 (95%CI 2.0-3.6), adjusted risk difference (aRD) 10.5% (95%CI 5.4-15.7). In a sensitivity analysis excluding all diagnosed chromosomal abnormalities, the risk of preterm birth remained elevated to a similar degree: aRR 2.6 (95%CI 1.9-3.7), aRD 10.0% (95%CI 4.8-15.3). The risk of other adverse perinatal outcomes was also higher, including the risk of chromosomal abnormalities other than trisomies 21 and 18: aRR 81.1 (95%CI 69.4-94.8), aRD 34.0% (95%CI 29.2-38.8). Pregnancies with double-positive results were also less likely to result in a live birth, even when excluding all diagnosed chromosomal abnormalities; and at increased risk of adverse perinatal outcomes for those resulting in a live birth. CONCLUSION: Although rare, double-positive multiple marker screening results are associated with an increased risk of preterm birth and other adverse perinatal outcomes, even when excluding all identified chromosomal abnormalities.

Preregistration in practice: A comparison of preregistered and non-preregistered studies in psychology.

Preregistration has gained traction as one of the most promising solutions to improve the replicability of scientific effects. In this project, we compared 193 psychology studies that earned a Preregistration Challenge prize or preregistration badge to 193 related studies that were not preregistered. In contrast to our theoretical expectations and prior research, we did not find that preregistered studies had a lower proportion of positive results (Hypothesis 1), smaller effect sizes (Hypothesis 2), or fewer statistical errors (Hypothesis 3) than non-preregistered studies. Supporting our Hypotheses 4 and 5, we found that preregistered studies more often contained power analyses and typically had larger sample sizes than non-preregistered studies. Finally, concerns about the publishability and impact of preregistered studies seem unwarranted, as preregistered studies did not take longer to publish and scored better on several impact measures. Overall, our data indicate that preregistration has beneficial effects in the realm of statistical power and impact, but we did not find robust evidence that preregistration prevents p-hacking and HARKing (Hypothesizing After the Results are Known).

Evaluation and clinical implications of the time to a positive results of antigen testing for SARS-CoV-2.

INTRODUCTION: Antigen tests for severe acute respiratory coronavirus 2 sometimes show positive lines earlier than their specified read time, although the implication of getting the results at earlier time is not well understood. METHODS: We prospectively collected additional nasopharyngeal samples from patients who had already tested positive for SARS-CoV-2 by reverse transcription PCR. The swab was used for an antigen test, QuickNavi™-COVID19 Ag, and the time periods to get positive results were measured. RESULTS: In 84 of 96 (87.5%) analyzed cases, the results of QuickNavi™-COVID19 Ag were positive. The time to obtain positive results was 15.0 seconds in median (inter quartile range: 12.0-33.3, range 11-736) and was extended in samples with higher cycle thresholds (p < 0.001). Positive lines appeared within a minute in 85.7% of cases and within 5 min in 96.4%. CONCLUSION: QuickNavi™-COVID19 Ag immediately showed positive results in most cases, and the time to a positive reaction may have indicated the viral load.

A study of the moving rate of positive results for use in a patient-based real-time quality control program on a procalcitonin point-of-care testing analyzer.

OBJECTIVE: To establish an applicable and highly sensitive patient-based real-time quality control (PBRTQC) program based on a data model constructed with patients' results of a procalcitonin point-of-care testing (POCT) analyzer. METHODS: Patients' results were retrospectively collected within one year. The Excel software was used to establish quality control (QC) programs of the moving average (MA) and the moving rate of positive results (MR). A Monte Carlo simulation was used to introduce positive and negative biases between 0.01 and 1 ng/ml at random points of the testing data set. Different parameters were used to detect the biases, and the detection efficiency was expressed using the median number of patient samples affected until error detection (MNPed). After comparing the MNPeds of different programs, MA and MR programs with appropriate parameters were selected, and validation plots were generated using MNPeds and maximum number of the patient samples affected (MAX). ß curves were generated using the power function of the programs, the performances were compared with that of the conventional QC program. RESULTS: Neither the conventional QC nor MA program was sensitive to small bias, While MR program can detect the minimum positive bias of 0.06 ng/ml and negative of 0.4 ng/ml at an average daily run size of 10 specimens, with FRs < 1.0%, ßs < 1%. CONCLUSION: The MR program, which is more sensitive to small biases than conventional QC and MA programs, with low FR and ß. As such, it can be used as a PBRTQC program with high performance.

The failure of drug repurposing for COVID-19 as an effect of excessive hypothesis testing and weak mechanistic evidence.

The current strategy of searching for an effective treatment for COVID-19 relies mainly on repurposing existing therapies developed to target other diseases. Conflicting results have emerged in regard to the efficacy of several tested compounds but later results were negative. The number of conducted and ongoing trials and the urgent need for a treatment pose the risk that false-positive results will be incorrectly interpreted as evidence for treatments' efficacy and a ground for drug approval. Our purpose is twofold. First, we show that the number of drug-repurposing trials can explain the false-positive results. Second, we assess the evidence for treatments' efficacy from the perspective of evidential pluralism and argue that considering mechanistic evidence is particularly needed in cases when the evidence from clinical trials is conflicting or of low quality. Our analysis is an application of the program of Evidence Based Medicine Plus (EBM+) to the drug repurposing trials for COVID. Our study shows that if decision-makers applied EBM+, authorizing the use of ineffective treatments would be less likely. We analyze the example of trials assessing the efficacy of hydroxychloroquine as a treatment for COVID-19 and mechanistic evidence in favor of and against its therapeutic power to draw a lesson for decision-makers and drug agencies on how excessive hypothesis testing can lead to spurious findings and how studying negative mechanistic evidence can be helpful in discriminating genuine from spurious results.

Second- and third-generation commercial Neisseria gonorrhoeae screening assays and the ongoing issues of false-positive results and confirmatory testing.

Supplementary nucleic acid amplification tests for Neisseria gonorrhoeae (NG) are widely used to circumvent specificity problems often associated with extragenital sites. This study was prompted by our observations and concerns from local sexual health physicians over increased discrepancies between Roche cobas 4800 CT/NG (c4800) and our in-house supplementary NG-PCR (NG-duplex) for oropharyngeal samples, when compared with Abbott RealTime CT/NG (m2000) performed prior. Here, we investigated these differences. Three banks of NG-positive samples were used. Bank 1 (n = 344) were screened using m2000. Banks 2 (n = 344) and 3 (n = 400) were screened using c4800. Remnant nucleic acids from all banks were tested using NG-duplex as part of routine testing. Bank 2 samples were further tested using m2000, some selectively tested using Cepheid Xpert CT/NG. Bank 3 samples were further tested using cobas CT/NG (cobas 6800 system). Confirmatory rates were significantly (p < 0.0001) higher for m2000 compared with c4800, with oropharyngeal samples the key difference. However, we also showed that our NG-duplex failed to confirm some true-positive NG samples. Using an expanded gold standard, confirmatory rates for m2000 and c4800 exceeded 90% for all anatomical sites with the exception of c4800 for oropharyngeal specimens at 78%. The observed discrepancies were due to a combination of c4800 producing false-positive results for oropharyngeal samples as well as sensitivity issues related to the NG-duplex assay. The data highlight the ongoing need for NG supplemental nucleic acid testing for oropharyngeal samples but also emphasise the need for careful selection of supplementary methods.

Digestive enzymes of fungal origin as a relevant cause of false positive Aspergillus antigen testing in intensive care unit patients.

BACKGROUND: Galactomannan antigen (GM) testing is widely used in the diagnosis of invasive aspergillosis (IA). Digestive enzymes play an important role in enzyme substitution therapy in exocrine pancreatic insufficiency. As digestive enzymes of fungal origin like Nortase contain enzymes from Aspergillus, a false-positive result of the test might be possible because of cross-reacting antigens of the cell wall of the producing fungi. We, therefore, asked whether the administration of fungal enzymes is a relevant cause of false-positive GM antigen test results. METHODS: Patients with a positive GM antigen test between January 2016 and April 2020 were included in the evaluation and divided into two groups: group 1-Nortase-therapy, group 2-no Nortase-therapy. In addition, dissolved Nortase samples were analyzed in vitro for GM and ß-1,3-D-glucan. For statistical analysis, the chi-squared and Mann‒Whitney U tests were used. RESULTS: Sixty-five patients were included in this evaluation (30 patients receiving Nortase and 35 patients not receiving Nortase). The overall false positivity rate of GM testing was 43.1%. Notably, false-positive results were detected significantly more often in the Nortase group (73.3%) than in the control group (17.1%, p < 0.001). While the positive predictive value of GM testing was 0.83 in the control group, there was a dramatic decline to 0.27 in the Nortase group. In vitro analysis proved that the Nortase enzyme preparation was highly positive for the fungal antigens GM and ß-1,3-D-glucan. CONCLUSIONS: Our data demonstrate that the administration of digestive enzymes of fungal origin like Nortase leads to a significantly higher rate of false-positive GM test results compared to that in patients without digestive enzyme treatment.

Alleviating psychological distress associated with a positive cervical cancer screening result: a randomized control trial.

BACKGROUND: The method of communicating a positive cancer screening result should seek to alleviate psychological distress associated with a positive result. We evaluated whether the provision of information through a leaflet would help reduce psychological distress in a randomized controlled trial. METHODS: The participants were women aged 20-69 years who were about to undergo cervical cancer screening at health centers. Before the screening, they received hypothetical screening results, with a leaflet (intervention group, n = 493) or without it (control group, n = 479), randomly. Their psychological distress and intention to undergo further examination were then compared between the intervention and control groups. RESULTS: After the intervention (providing a leaflet with hypothetical screening results), psychological distress appeared to be higher in the control group than in the intervention group among those who received a hypothetical positive screening result (odds ratio: 2.57, 95% confidence interval: 1.87-3.54), while 95% and 97% of those in the intervention and control groups, respectively, reported that they would undergo further examination. CONCLUSIONS: Information provision might help reduce psychological distress but not hinder further examination among women who screen positive for cervical cancer. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000029894. Date of Registration: November 2017.

CAN IgG ANTIBODIES DIRECTED AGAINST DIFFERENT TARGETS SOLVE THE PROBLEM OF FALSE-POSITIVE RESULTS IN SARS-CoV-2 SEROLOGY?

In addition to RT-PCR assays, serology testing that has been recognized as a useful tool to assess the spread of infection in the population is considered successful and important strategy in the control of the global pandemic of SARS-CoV-2 infection. Now, a great number of manufacturers offer their serologic tests on the market. When interpretating the results, the rate of seroprevalence should be taken in consideration because it may influence the positive predictive value, as well as cross-reactivity with other coronaviruses in case of assays with poorly designed antigens. We present results of 11 patients with different clinical background and tested with two different serologic tests, DIAPRO (ELISA; Sesto San Giovanni, Italy) and VIDAS (ELFA; BioMerieux, Marcy I'Etoile, France). The results obtained by the former test showed ten of these patients to be IgG positive and one patient was IgG weakly positive with different confidence index. The latter test discriminated positive results with medium confidence index on the former test as negative. The results obtained with two serology tests were concordant with the observation that the results with medium confidence index may indicate cross-reactivity.

Comparing prenatal screening experiences of Icelandic women who received false-positive and true-negative first-trimester combined screening results in Iceland in 2012-2016.

First-trimester combined screening (FTS) has been offered to all pregnant women in Iceland since 2003. Individuals with high-risk FTS results are offered an invasive test option with a ≤1% risk of fetal loss. This study gives insight into the prenatal screening and diagnosis experiences and preferences of 101 women who underwent FTS in Iceland in the years 2012-2016, comparing the experience of those who received false-positive FTS results to those who received true-negative results. Retrospective patient-reported anxiety levels at the time of receiving FTS results were significantly higher in those who received false-positive results compared to those who received true-negative results. For a subset of these participants, the anxiety lasted through pregnancy, and for a smaller subset, it lasted even longer. Non-invasive prenatal testing (NIPT) is currently not offered in Iceland, aside from the rare exceptional case. Given the extremely low false-positive rates of NIPT, we believe NIPT is worth considering as Iceland's standard first-tier screening method for trisomy 13, 18, and 21. We believe the findings of this study are beneficial not only for Iceland but also for other countries where FTS is the first-tier prenatal screening method or the only offered test. Additionally, only 21% of participants in our study reported that they had heard of NIPT, which emphasizes the need for comprehensive NIPT pretest information to be available prior to its uptake to ensure informed and autonomous decision-making.

Selection bias for treatments with positive Phase 2 results.

In drug development, treatments are most often selected at Phase 2 for further development when an initial trial of a new treatment produces a result that is considered positive. This selection due to a positive result means, however, that an estimator of the treatment effect, which does not take account of the selection is likely to over-estimate the true treatment effect (ie, will be biased). This bias can be large and researchers may face a disappointingly lower estimated treatment effect in further trials. In this paper, we review a number of methods that have been proposed to correct for this bias and introduce three new methods. We present results from applying the various methods to two examples and consider extensions of the examples. We assess the methods with respect to bias of estimation of the treatment effect and compare the probabilities that a bias-corrected treatment effect estimate will exceed a decision threshold. Following previous work, we also compare average power for the situation where a Phase 3 trial is launched given that the bias-corrected observed Phase 2 treatment effect exceeds a launch threshold. Finally, we discuss our findings and potential application of the bias correction methods.

A case of Mycobacterium tuberculosis laboratory cross-contamination.

SETTING: A laboratory cross-contamination event was suspected because Mycobacterium tuberculosis was unexpectedly detected at a high incidence in the cultures of several clinical specimens at the National Hospital Organization, Tokyo National Hospital, Japan. OBJECTIVE: To describe a case of Mycobacterium tuberculosis laboratory cross-contamination. DESIGN: We reviewed the medical records of 20 patients whose clinical specimens were suspected to have been contaminated by Mycobacterium tuberculosis. Variable number of tandem repeat analysis with 15 loci, the Japan Anti-Tuberculosis Association-12, and three additional hyper-variable loci, was performed to identify the cross-contamination event. RESULTS: The clinical, laboratory, and variable number of tandem repeat data revealed that the cross-contamination had possibly originated from one strongly positive specimen, resulting in false-positive results in 11 other specimens, including a case treated with anti-tuberculosis drugs. CONCLUSION: Clinical and laboratory data must be re-evaluated when cross-contamination is suspected and variable number of tandem repeat analysis should be used to confirm cross-contamination. Furthermore, original isolates should be stored appropriately, without sub-culturing and genotyping should be performed at the earliest possible for better utilization of variable number of tandem repeat for the identification of cross-contamination.

Mosaic maternal 10qter deletions are associated with FRA10B expansions and may cause false-positive noninvasive prenatal screening results.

PURPOSE: Using genome-wide noninvasive prenatal screening (NIPS), we detected a 20-megabase specific deletion starting at 10q25 in eight pregnancies. The deletion could not be confirmed by invasive testing. Since all 10(q25→qter) deletions started close to the FRA10B fragile site in 10q25, we investigated whether the pregnant women were indeed carriers of FRA10B. METHODS: We performed NIPS analysis for all autosomes using single-read sequencing. Analysis was done with the WISECONDOR algorithm. Culture of blood lymphocytes with bromodeoxyuridine was used to detect FRA10B expansions. Fluorescence in situ hybridization and array analysis were used to find maternal and/or fetal deletions. RESULTS: We confirmed the presence of a FRA10B expansion in all four tested mothers. Fluorescence in situ hybridization and array analysis confirmed the presence of a maternal mosaic deletion of 10(q25→qter). CONCLUSION: The recurring 10(q25→qter) deletion detected with NIPS is a false-positive result caused by a maternal low-level mosaic deletion associated with FRA10B expansions. This has important consequences for clinical follow-up, as invasive procedures are unnecessary. Expanded maternal FRA10B repeats should be added to the growing group of variants in the maternal genome that may cause false-positive NIPS results.

Secular trends in the impact factors of SLE publications over a 45-year period-a systematic review.

OBJECTIVE: We assessed publication bias in the field of systemic lupus erythematosus (SLE) by conducting a search of randomized, controlled trials (RCTs) on SLE therapies that had been published over the past 45 years. Our aim was to assess a potential publication bias by determining whether RCTs reporting positive results, RCTs with placebo arms, biologics RCTs, and industry-funded RCTs are more likely to be published in journals with higher impact factors (IFs). METHODS: We conducted a systematic review of all RCTs registered in PubMed between 1 January 1975 and 1 November 2016. Each RCT was classified as having a positive result (PR) or a negative result (NR). The IF of each journal was determined for the year of publication. RESULTS: Our search yielded 233 relevant RCTs. There was no significant difference in IFs between studies with NRs and those with PRs or between studies that were financially supported by commercial companies compared to studies that were not. However, there was a significant correlation between sample size and the journal's IF. CONCLUSIONS: IF scores of RCTs in the field of SLE are influenced by sample size and not biased by either a tendency to report PRs or by being funded by pharmaceutical companies or any other commercial sources.

Anti-streptavidin IgG antibody interference in anti-cyclic citrullinated peptide (CCP) IgG antibody assays is a rare but important cause of false-positive anti-CCP results.

BACKGROUND: The detection of anti-cyclic citrullinated peptide (anti-CCP) IgG antibodies in blood is mainly used for the diagnosis of rheumatoid arthritis. Falsely elevated anti-CCP IgG antibodies due to anti-streptavidin IgG antibodies were suspected in our laboratory. METHODS: In this study, we evaluated, in a standardized approach, the prevalence of anti-streptavidin IgG antibodies in a primary care setting and the effect of anti-streptavidin IgG antibodies on anti-CCP IgG assays from three different important commercial manufacturers (Abbott, Roche Diagnostics, Thermo Fisher Scientific). Three different populations were consecutively and prospectively studied: serum samples from 1000 ambulatory patients, 286 serum samples from patients for which anti-CCP was requested and 89 serum samples from patients which had previously given a positive anti-CCP result on Architect® i2000. RESULTS: The frequency of confirmed anti-streptavidin IgG-positive samples detected in this study was 0.6% (8/1375). Anti-CCP IgG was determined on the eight samples with confirmed anti-streptavidin IgG antibodies: with the Cobas® method, seven positive anti-CCP results were observed and five positive anti-CCP results with the Architect® method. No positive anti-CCP IgG results were obtained with the EliA™ method. Rheumatoid factor was negative in these eight samples. CONCLUSIONS: Anti-streptavidin IgG antibodies rarely cause false-positive results in some anti-CCP assays. However, despite being an infrequent assay problem, it could possibly lead to diagnostic confusion or even an incorrect diagnosis of rheumatoid arthritis.

College football, elections, and false-positive results in observational research.

A recent, widely cited study [Healy AJ, Malhotra N, Mo CH (2010) Proc Natl Acad Sci USA 107(29):12804-12809] finds that college football games influence voting behavior. Victories within 2 weeks of an election reportedly increase the success of the incumbent party in presidential, senatorial, and gubernatorial elections in the home county of the team. We reassess the evidence and conclude that there is likely no such effect, despite the fact that Healy et al. followed the best practices in social science and used a credible research design. Multiple independent sources of evidence suggest that the original finding was spurious-reflecting bad luck for researchers rather than a shortcoming of American voters. We fail to estimate the same effect when we leverage situations where multiple elections with differing incumbent parties occur in the same county and year. We also find that the purported effect of college football games is stronger in counties where people are less interested in college football, just as strong when the incumbent candidate does not run for reelection, and just as strong in other parts of the state outside the home county of the team. Lastly, we detect no effect of National Football League games on elections, despite their greater popularity. We conclude with recommendations for evaluating surprising research findings and avoiding similar false-positive results.

[Lung cancer screening: current trends]. / Lungenkrebsscreening: Aktuelle Entwicklungen.

Screening studies on conventional chest X­rays and on sputum cytology did not show a reduction in lung cancer mortality. However, screening by low-dose computed tomography (LDCT) is more promising because it allows tumor detection in early stages at fairly low radiation levels. No reduction of lung cancer mortality was found in two small, randomized clinical studies on LDCT screening in Europe. However, in the by far largest LDCT trial, the National Lung Screening Trial (NLST) in the USA, a relative reduction of lung cancer mortality by 20.0% (95% confidence interval: 6.8-26.7%), and a relative reduction of total mortality by 6.7% (95% CI: 1.2-13.6%) was reported. According to the NLST, an important disadvantage of LDCT is the low positive predictive value of abnormal screening results: lung cancer was confirmed in only 4 of 100 abnormal screening results.In this paper, benefits and disadvantages of LDCT screening and related open questions are systematically discussed. A possible reduction of lung cancer specific and total mortality must be weighed against false positive results, overdiagnoses, and radiation exposure. In NLST, the proportion of overdiagnoses is estimated to be 11.0 to 18.5%, depending on the strategy of analysis; radiation exposure is about 1.5 mSv per scan, and thus much lower than radiation exposure in chest X­ray, which is about 8 mSv per scan. Open questions refer to who should be offered the screening, how long the time intervals between screening rounds should be, and which algorithms should be used to clarify screen-detected nodules.

Assessment of skin sensitization under REACH: A case report on vehicle choice in the LLNA and its crucial role preventing false positive results.

In the EU, chemicals with a production or import volume in quantities of one metric ton per year or more have to be tested for skin sensitizing properties under the REACH regulation. The murine Local Lymph Node Assay (LLNA) and its modifications are widely used to fulfil the data requirement, as it is currently considered the first-choice method for in vivo testing to cover this endpoint. This manuscript describes a case study highlighting the importance of understanding the chemistry of the test material during testing for 'skin sensitization' of MCDA (mixture of 2,4- and 2,6-diamino-methylcyclohexane) with particular focus on the vehicle used. While the BrdU-ELISA modification of the LLNA using acetone/olive oil (AOO) as vehicle revealed expectable positive results. However, the concentration control analysis unexpectedly revealed an instability of MCDA in the vehicle AOO. Further studies on the reactivity showed MCDA to rapidly react with AOO under formation of various imine structures, which might have caused the positive LLNA result. The repetition of the LLNA using propylene glycol (PG) as vehicle did not confirm the positive results of the LLNA using AOO. Finally, a classification of MCDA as skin sensitizer according to the Globally Harmonized System (GHS) was not justified.

Experiences among Women with Positive Prenatal Expanded Carrier Screening Results.

The offering and acceptance of expanded carrier screening is increasing among pregnant women including women without an increased risk based on race, ethnicity or family history. The chances of a positive screening test have been reported to be as high as 24 % when multiple conditions are screened. Yet, little is known about the way these tests are offered and how patients are affected by a positive test result. To explore this area of genetic testing, interviews (n = 17) were conducted among women who received positive expanded carrier results in the context of obstetric care. A content analysis was conducted on the transcript data from the interviews. Outcomes of this research suggest that educational interventions are needed to improve maternal understanding of positive carrier screening results. Most of the participants in this study confused the results with other prenatal screening test options. In addition, the way the results were discussed varied greatly, and influenced participants' thoughts about reproductive decisions that led to a range of emotional uncertainty. Our data suggests that genetic counseling improved participants' understanding of positive results. More research is needed to further understand if our results are consistent within a larger, more diverse sample, and to explore how to best provide education about expanded carrier screening.

[False positive results or what's the probability that a significant P-value indicates a true effect?] / Les résultats faux positifs ou quelle est la probabilité que le traitement soit efficace quand p < 0,05 ?

The use of statistical test is central in the clinical trial. At the statistical level, obtaining a P<0.05 allows to claim the effectiveness of the new studied treatment. However, given its underlying mathematical logic the concept of "P value" is often misinterpreted. It is often assimilated, mistakenly, to the likelihood that treatment is ineffective. Actually the "P value" gives an indirect information about the plausibility of the existence of treatment effect. With "P<0.05", the probability that the treatment is effective may vary depending on other statistical parameters which are the alpha level of risk, the power of the study and especially the a priori probability of the existence of treatment effect. A "P<0.05" does not always produce the same degree of certainty. Thus there exist situations where the risk of a result "P<0.05" is in reality a false positive is very high. This is the case if the power is low, if there is an inflation of the alpha risk or if the result is exploratory or chance discoveries. This possibility is important to take into consideration when interpreting the results of clinical trials in order to avoid pushing ahead significant results in appearance, but which are likely to be actually false positive results.