PLoS clinical trials最新文献

{"title":"Three drug combinations for late-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Uganda.","authors":"Gerardo Priotto,&nbsp;Carole Fogg,&nbsp;Manica Balasegaram,&nbsp;Olema Erphas,&nbsp;Albino Louga,&nbsp;Francesco Checchi,&nbsp;Salah Ghabri,&nbsp;Patrice Piola","doi":"10.1371/journal.pctr.0010039","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010039","url":null,"abstract":"<p><strong>Objectives: </strong>Our objective was to compare the efficacy and safety of three drug combinations for the treatment of late-stage human African trypanosomiasis caused by Trypanosoma brucei gambiense.</p><p><strong>Design: </strong>This trial was a randomized, open-label, active control, parallel clinical trial comparing three arms.</p><p><strong>Setting: </strong>The study took place at the Sleeping Sickness Treatment Center run by Médecins Sans Frontières at Omugo, Arua District, Uganda</p><p><strong>Participants: </strong>Stage 2 patients diagnosed in Northern Uganda were screened for inclusion and a total of 54 selected.</p><p><strong>Interventions: </strong>Three drug combinations were given to randomly assigned patients: melarsoprol-nifurtimox (M+N), melarsoprol-eflornithine (M+E), and nifurtimox-eflornithine (N+E). Dosages were uniform: intravenous (IV) melarsoprol 1.8 mg/kg/d, daily for 10 d; IV eflornithine 400 mg/kg/d, every 6 h for 7 d; oral nifurtimox 15 (adults) or 20 (children <15 y) mg/kg/d, every 8 h for 10 d. Patients were followed up for 24 mo.</p><p><strong>Outcome measures: </strong>Outcomes were cure rates and adverse events attributable to treatment.</p><p><strong>Results: </strong>Randomization was performed on 54 patients before enrollment was suspended due to unacceptable toxicity in one of the three arms. Cure rates obtained with the intention to treat analysis were M+N 44.4%, M+E 78.9%, and N+E 94.1%, and were significantly higher with N+E (p = 0.003) and M+E (p = 0.045) than with M+N. Adverse events were less frequent and less severe with N+E, resulting in fewer treatment interruptions and no fatalities. Four patients died who were taking melarsoprol-nifurtimox and one who was taking melarsoprol-eflornithine.</p><p><strong>Conclusions: </strong>The N+E combination appears to be a promising first-line therapy that may improve treatment of sleeping sickness, although the results from this interrupted study do not permit conclusive interpretations. Larger studies are needed to continue the evaluation of this drug combination in the treatment of T. b. gambiense sleeping sickness.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26434693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and allele-specific immunogenicity of a malaria vaccine in Malian adults: results of a phase I randomized trial.","authors":"Mahamadou A Thera,&nbsp;Ogobara K Doumbo,&nbsp;Drissa Coulibaly,&nbsp;Dapa A Diallo,&nbsp;Issaka Sagara,&nbsp;Alassane Dicko,&nbsp;David J Diemert,&nbsp;D Gray Heppner,&nbsp;V Ann Stewart,&nbsp;Evelina Angov,&nbsp;Lorraine Soisson,&nbsp;Amanda Leach,&nbsp;Kathryn Tucker,&nbsp;Kirsten E Lyke,&nbsp;Christopher V Plowe","doi":"10.1371/journal.pctr.0010034","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010034","url":null,"abstract":"<p><strong>Objectives: </strong>The objectives were to evaluate the safety, reactogenicity, and allele-specific immunogenicity of the blood-stage malaria vaccine FMP1/AS02A in adults exposed to seasonal malaria and the impact of natural infection on vaccine-induced antibody levels.</p><p><strong>Design: </strong>We conducted a randomized, double-blind, controlled phase I clinical trial.</p><p><strong>Setting: </strong>Bandiagara, Mali, West Africa, is a rural town with intense seasonal transmission of Plasmodium falciparum malaria.</p><p><strong>Participants: </strong>Forty healthy, malaria-experienced Malian adults aged 18-55 y were enrolled.</p><p><strong>Interventions: </strong>The FMP1/AS02A malaria vaccine is a 42-kDa recombinant protein based on the carboxy-terminal end of merozoite surface protein-1 (MSP-1(42)) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The control vaccine was a killed rabies virus vaccine (Imovax). Participants were randomized to receive either FMP1/AS02A or rabies vaccine at 0, 1, and 2 mo and were followed for 1 y.</p><p><strong>Outcome measures: </strong>Solicited and unsolicited adverse events and allele-specific antibody responses to recombinant MSP-1(42) and its subunits derived from P. falciparum strains homologous and heterologous to the 3D7 vaccine strain were measured.</p><p><strong>Results: </strong>Transient local pain and swelling were more common in the malaria vaccine group than in the control group (11/20 versus 3/20 and 10/20 versus 6/20, respectively). MSP-1(42) antibody levels rose during the malaria transmission season in the control group, but were significantly higher in malaria vaccine recipients after the second immunization and remained higher after the third immunization relative both to baseline and to the control group. Immunization with the malaria vaccine was followed by significant increases in antibodies recognizing three diverse MSP-1(42) alleles and their subunits.</p><p><strong>Conclusions: </strong>FMP1/AS02A was well tolerated and highly immunogenic in adults exposed to intense seasonal malaria transmission and elicited immune responses to genetically diverse parasite clones. Anti-MSP-1(42) antibody levels followed a seasonal pattern that was significantly augmented and prolonged by the malaria vaccine.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1851722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26404844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children.","authors":"Mark R Withers, Denise McKinney, Bernhards R Ogutu, John N Waitumbi, Jessica B Milman, Odika J Apollo, Otieno G Allen, Kathryn Tucker, Lorraine A Soisson, Carter Diggs, Amanda Leach, Janet Wittes, Filip Dubovsky, V Ann Stewart, Shon A Remich, Joe Cohen, W Ripley Ballou, Carolyn A Holland, Jeffrey A Lyon, Evelina Angov, José A Stoute, Samuel K Martin, D Gray Heppner","doi":"10.1371/journal.pctr.0010032","DOIUrl":"10.1371/journal.pctr.0010032","url":null,"abstract":"<p><strong>Objective: </strong>Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine.</p><p><strong>Design: </strong>This was an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator.</p><p><strong>Setting: </strong>The study was conducted in a rural population in Kombewa Division, western Kenya.</p><p><strong>Participants: </strong>Subjects were 135 children, aged 12-47 mo.</p><p><strong>Interventions: </strong>Subjects received 10, 25, or 50 microg of falciparum malaria protein 1 (FMP1) formulated in 100, 250, and 500 microL, respectively, of AS02A, or they received a comparator (Imovax (rabies vaccine).</p><p><strong>Outcome measures: </strong>We performed safety and reactogenicity parameters and assessment of adverse events during solicited (7 d) and unsolicited (30 d) periods after each vaccination. Serious adverse events were monitored for 6 mo after the last vaccination.</p><p><strong>Results: </strong>Both vaccines were safe and well tolerated. FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship. Systemic reactogenicity was low at all dose levels. Hemoglobin levels remained stable and similar across arms. Baseline geometric mean titers were comparable in all groups. Anti-FMP1 antibody titers increased in a dose-dependent manner in subjects receiving FMP1/AS02A; no increase in anti-FMP1 titers occurred in subjects who received the comparator. By study end, subjects who received either 25 or 50 microg of FMP1 had similar antibody levels, which remained significantly higher than that of those who received the comparator or 10 microg of FMP1. A longitudinal mixed effects model showed a statistically significant effect of dosage level on immune response (F(3,1047) = 10.78, or F(3, 995) = 11.22, p < 0.001); however, the comparison of 25 microg and 50 microg recipients indicated no significant difference (F(1,1047) = 0.05; p = 0.82).</p><p><strong>Conclusions: </strong>The FMP1/AS02A vaccine was safe and immunogenic in malaria-exposed 12- to 47-mo-old children and the magnitude of immune response of the 25 and 50 microg doses was superior to that of the 10 microg dose.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1851726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26404843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT).","authors":"","doi":"10.1371/journal.pctr.0010033","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010033","url":null,"abstract":"<p><strong>Objectives: </strong>The Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) was designed to evaluate the conventional NSAID naproxen sodium and the selective COX-2 inhibitor celecoxib for primary prevention of Alzheimer's dementia (AD). On 17 December 2004, after the Adenoma Prevention with Celecoxib (APC) trial reported increased cardiovascular risks with celecoxib, the ADAPT Steering Committee suspended treatment and enrollment. This paper reports on cardiovascular and cerebrovascular events in ADAPT.</p><p><strong>Design: </strong>ADAPT is a randomized, placebo-controlled, parallel chemoprevention trial with 1-46 mo of follow-up.</p><p><strong>Setting: </strong>The trial was conducted at six field sites in the United States: Baltimore, Maryland; Boston, Massachusetts; Rochester, New York; Seattle, Washington; Sun City, Arizona; and Tampa, Florida.</p><p><strong>Participants: </strong>The 2,528 participants were aged 70 y and older with a family history of AD.</p><p><strong>Interventions: </strong>Study treatments were celecoxib (200 mg b.i.d.), naproxen sodium (220 mg b.i.d.), and placebo.</p><p><strong>Outcome measures: </strong>Outcome measures were deaths, along with nonfatal myocardial infarction (MI), stroke, congestive heart failure (CHF), transient ischemic attack (TIA), and antihypertensive treatment recorded from structured interviews at scheduled intervals. Cox proportional hazards regression was used to analyze these events individually and in several composites.</p><p><strong>Results: </strong>Counts (with 3-y incidence) of participants who experienced cardiovascular or cerebrovascular death, MI, stroke, CHF, or TIA in the celecoxib-, naproxen-, and placebo-treated groups were 28/717 (5.54%), 40/713 (8.25%), and 37/1070 (5.68%), respectively. This yielded a hazard ratio (95% confidence interval [CI]) for celecoxib of 1.10 (0.67-1.79) and for naproxen of 1.63 (1.04-2.55). Antihypertensive treatment was initiated in 160/440 (47.43%), 147/427 (45.00%), and 164/644 (34.08%). This yielded hazard ratios (CIs) of 1.56 for celecoxib (1.26-1.94) and 1.40 for naproxen (1.12-1.75).</p><p><strong>Conclusions: </strong>For celecoxib, ADAPT data do not show the same level of risk as those of the APC trial. The data for naproxen, although not definitive, are suggestive of increased cardiovascular and cerebrovascular risk.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26369407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAPT: the wrong way to stop a clinical trial.","authors":"Steven E Nissen","doi":"10.1371/journal.pctr.0010035","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010035","url":null,"abstract":"","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26369411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution and translation of research findings: from bench to where?","authors":"John P A Ioannidis","doi":"10.1371/journal.pctr.0010036","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010036","url":null,"abstract":"<p><p>The credibility and replication of research findings evolve over time, as data accumulate. However, translation of postulated research promises to real-life biomedical applications is uncommon. In some fields of research, we may observe diminishing effects for the strength of research findings and rapid alternations of exaggerated claims and extreme contradictions--the \"Proteus Phenomenon.\" While these phenomena are probably more prominent in the basic sciences, similar manifestations have been documented even in clinical trials and they may undermine the credibility of clinical research. Significance-chasing bias may be in part responsible, but the greatest threat may come from the poor relevance and scientific rationale and thus low pre-study odds of success of research efforts. Given that we currently have too many research findings, often with low credibility, replication and rigorous evaluation become as important as or even more important than discovery. Credibility, replication, and translation are all desirable properties of research findings, but are only modestly correlated. In this essay, I discuss some of the evidence (or lack thereof) for the process of evolution and translation of research findings, with emphasis on the biomedical sciences.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26369410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Volume Expansion with Albumin Compared to Gelofusine in Children with Severe Malaria: Results of a Controlled Trial","authors":"S. Akech, Samson Gwer, R. Idro, G. Fegan, A. C. Eziefula, C. Newton, M. Levin, K. Maitland","doi":"10.1371/journal.pctr.0010037","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010037","url":null,"abstract":"What this trial shows: The investigators found no significant differences in the primary outcomes (correction of shock and acidosis in the blood 8 h after fluids were started) or in death rates between children given Gelofusine and those given albumin. The researchers then combined the data on death rates from this trial with data from two other trials with an albumin arm. This combined analysis suggested that death rates with albumin were lower than with other fluids, either Gelofusine or salt solution.","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66664454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the evidence base for trauma care: progress in the international CRASH-2 trial.","authors":"","doi":"10.1371/journal.pctr.0010030","DOIUrl":"10.1371/journal.pctr.0010030","url":null,"abstract":"","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26336315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Publishing clinical trial results: the future beckons.","authors":"Elizabeth Wager","doi":"10.1371/journal.pctr.0010031","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010031","url":null,"abstract":"Elizabeth WagerSearch for the truth is the noblestoccupation of man; its publication is aduty. —Madame de Stael (1766–1817)Formats for reporting results fromrandomized clinical trials in peer-re-viewed journals have remained virtuallyunchanged and unchallenged for thepast 50 years [1]. However, a number ofdevelopments, some technological andsome political, provide exciting oppor-tunities to question whether we areusing the most efficient and effectivemethods of publication. Here, I suggesthow methods of reporting clinical trialscould be improved and consider theimplications for trial sponsors andmedical journals.","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26336314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 2b randomised trial of the candidate malaria vaccines FP9 ME-TRAP and MVA ME-TRAP among children in Kenya.","authors":"Philip Bejon,&nbsp;Jedidah Mwacharo,&nbsp;Oscar Kai,&nbsp;Tabitha Mwangi,&nbsp;Paul Milligan,&nbsp;Stephen Todryk,&nbsp;Sheila Keating,&nbsp;Trudie Lang,&nbsp;Brett Lowe,&nbsp;Caroline Gikonyo,&nbsp;Catherine Molyneux,&nbsp;Greg Fegan,&nbsp;Sarah C Gilbert,&nbsp;Norbert Peshu,&nbsp;Kevin Marsh,&nbsp;Adrian V S Hill","doi":"10.1371/journal.pctr.0010029","DOIUrl":"https://doi.org/10.1371/journal.pctr.0010029","url":null,"abstract":"<p><strong>Objective: </strong>The objective was to measure the efficacy of the vaccination regimen FFM ME-TRAP in preventing episodes of clinical malaria among children in a malaria endemic area. FFM ME-TRAP is sequential immunisation with two attenuated poxvirus vectors (FP9 and modified vaccinia virus Ankara), which both deliver the pre-erythrocytic malaria antigen construct multiple epitope-thrombospondin-related adhesion protein (ME-TRAP).</p><p><strong>Design: </strong>The trial was randomised and double-blinded.</p><p><strong>Setting: </strong>The setting was a rural, malaria-endemic area of coastal Kenya.</p><p><strong>Participants: </strong>We vaccinated 405 healthy 1- to 6-year-old children.</p><p><strong>Interventions: </strong>Participants were randomised to vaccination with either FFM ME-TRAP or control (rabies vaccine).</p><p><strong>Outcome measures: </strong>Following antimalarial drug treatment children were seen weekly and whenever they were unwell during nine months of monitoring. The axillary temperature was measured, and blood films taken when febrile. The primary analysis was time to a parasitaemia of over 2,500 parasites/mul.</p><p><strong>Results: </strong>The regime was moderately immunogenic, but the magnitude of T cell responses was lower than in previous studies. In intention to treat (ITT) analysis, time to first episode was shorter in the FFM ME-TRAP group. The cumulative incidence of febrile malaria was 52/190 (27%) for FFM ME-TRAP and 40/197 (20%) among controls (hazard ratio = 1.52). This was not statistically significant (95% confidence interval [CI] 1.0-2.3; p = 0.14 by log-rank). A group of 346 children were vaccinated according to protocol (ATP). Among these children, the hazard ratio was 1.3 (95% CI 0.8-2.1; p = 0.55 by log-rank). When multiple malaria episodes were included in the analyses, the incidence rate ratios were 1.6 (95% CI 1.1-2.3); p = 0.017 for ITT, and 1.4 (95% CI 0.9-2.1); p = 0.16 for ATP. Haemoglobin and parasitaemia in cross-sectional surveys at 3 and 9 mo did not differ by treatment group. Among children vaccinated with FFM ME-TRAP, there was no correlation between immunogenicity and malaria incidence.</p><p><strong>Conclusions: </strong>No protection was induced against febrile malaria by this vaccine regimen. Future field studies will require vaccinations with stronger immunogenicity in children living in malarious areas.</p>","PeriodicalId":87416,"journal":{"name":"PLoS clinical trials","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1371/journal.pctr.0010029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26319860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}