Publications (6)17.89 Total impact
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Article: On the independence of data monitoring committee in adaptive design clinical trials.
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ABSTRACT: In clinical trials, an independent data monitoring committee (DMC) is often established to perform both ongoing safety data monitoring and interim efficacy analysis. These evaluations are performed in a blinded fashion in order to avoid possible operational biases that may be introduced to the trial after the review of the data. The DMCs for clinical trials using adaptive design methods are also positioned to implement the adaptation decision according to the prospective adaptation algorithm. While the DMC plays an important role in maintaining the validity and integrity of the intended clinical trial, adaptive design clinical trials trigger a greater role and increased responsibility for the DMC. To assist the sponsor in establishing a DMC, the U.S. Food and Drug Administration (FDA) published a draft guidance entitled Establishment and Operation of Clinical Trial Data Monitoring Committees in 2006. In this article, the composition, role/responsibility, and function/activity of a DMC are described. Concerns of the additional responsibilities of the DMC for adaptive design clinical trials are addressed. Although the intention of the DMC is well-intentioned, controversial issues inevitably occur. These controversial issues include, but are not limited to, (1) the challenge of the independence of a DMC and (2) the issue regarding the direct communication between the DMC and the FDA. Discussion of controversial issues and practical issues are also provided.Journal of Biopharmaceutical Statistics 07/2012; 22(4):853-67. · 1.34 Impact Factor -
Article: Benefits, challenges and obstacles of adaptive clinical trial designs.
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ABSTRACT: In recent years, the use of adaptive design methods in pharmaceutical/clinical research and development has become popular due to its flexibility and efficiency for identifying potential signals of clinical benefit of the test treatment under investigation. The flexibility and efficiency, however, increase the risk of operational biases with resulting decrease in the accuracy and reliability for assessing the treatment effect of the test treatment under investigation. In its recent draft guidance, the United States Food and Drug Administration (FDA) expresses regulatory concern of controlling the overall type I error rate at a pre-specified level of significance for a clinical trial utilizing adaptive design. The FDA classifies adaptive designs into categories of well-understood and less well-understood designs. For those less well-understood adaptive designs such as adaptive dose finding designs and two-stage phase I/II (or phase II/III) seamless adaptive designs, statistical methods are not well established and hence should be used with caution. In practice, misuse of adaptive design methods in clinical trials is a concern to both clinical scientists and regulatory agencies. It is suggested that the escalating momentum for the use of adaptive design methods in clinical trials be slowed in order to allow time for development of appropriate statistical methodologies.Orphanet Journal of Rare Diseases 11/2011; 6:79. · 5.83 Impact Factor -
Article: Daptomycin compared to standard therapy for the treatment of native valve endocarditis.
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ABSTRACT: In a recent randomized trial of Staphylococcus aureus bacteremia and native valve endocarditis, daptomycin was found not inferior to standard therapy. We summarized findings in the subgroup of patients with endocarditis according to the Duke criteria. Patients were randomly assigned to receive daptomycin 6 mg/kg/day or standard therapy (vancomycin 1g every 12h or antistaphylococcal penicillin 2g every 4h, both with gentamicin 1mg/kg every 8h for the first 4 days). The primary end point was success in the modified intent-to-treat population 6 weeks after the end of therapy. Fifty-three patients were included: 35 with right-sided endocarditis (RIE) and 18 with left-sided endocarditis (LIE). The success rates in patients with RIE were similar between daptomycin and the comparator (42% vs 44%). Patients with RIE with septic pulmonary infarcts responded similarly to treatment with daptomycin and standard therapy (60% vs 67%). In the LIE population, treatment success rates were poor in both arms (11% vs 22%). Daptomycin is an efficacious and well-tolerated alternative to standard therapy in the treatment of RIE. Patients with LIE had a poor outcome regardless of the treatment received. Daptomycin is also effective in treating endocarditis with septic pulmonary infarcts.Enfermedades Infecciosas y Microbiología Clínica 02/2010; 28(8):498-503. · 1.49 Impact Factor -
Article: Genotypic characteristics of Staphylococcus aureus isolates from a multinational trial of complicated skin and skin structure infections.
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ABSTRACT: The impact of bacterial genetic characteristics on the outcome of patients with Staphylococcus aureus infections is uncertain. This investigation evaluated potential associations between bacterial genotype and clinical outcome using isolates collected as part of an international phase 2 clinical trial (FAST II) evaluating telavancin for the treatment of complicated skin and skin structure infections (cSSSI). Ninety S. aureus isolates from microbiologically evaluable patients with cSSSI enrolled in the FAST II trial from 11 sites in the United States (56 isolates, or 62%) and 7 sites in South Africa (34 isolates, or 38%) were examined for staphylococcal cassette chromosome mec, agr, and the presence of 31 virulence genes and subjected to pulsed-field gel electrophoresis (PFGE). South African methicillin-susceptible S. aureus (MSSA) isolates were more likely to carry certain virulence genes, including sdrD (P = 0.01), sea (P < 0.01), and pvl (P = 0.01). All 44 (49%) methicillin-resistant S. aureus (MRSA) isolates were from the United States; 37 (84%) were strain USA 300 by PFGE. In the United States, MRSA isolates were more likely than MSSA isolates to carry genes for sdrC (P = 0.03), map/eap (P = 0.05), fnbB (P = 0.11), tst (P = 0.02), sea (P = 0.04), sed (P = 0.04), seg (P = 0.11), sej (P = 0.11), agr (P = 0.09), V8 (P = 0.06), sdrD, sdrE, eta, etb, and see (P < 0.01 for all). MRSA isolates were more often clonal than MSSA isolates by PFGE. Isolates from patients who were cured were significantly more likely to contain the pvl gene than isolates from patients that failed or had indeterminate outcomes (79/84 [94%] versus 3/6 [50%]; P = 0.01). S. aureus strains from different geographic regions have different distributions of virulence genes.Journal of clinical microbiology 02/2008; 46(2):678-84. · 4.16 Impact Factor -
Article: Clinical characteristics and outcome of aortic endocarditis with periannular abscess in the International Collaboration on Endocarditis Merged Database.
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ABSTRACT: The aims of this study were to determine the clinical characteristics and outcome of patients who had definite infective endocarditis (IE) complicated by aortic ring abscess formation that was detected with transesophageal echocardiography (TEE) and to determine the prognostic significance of abscess formation in aortic valve IE. Patients who had aortic valve IE were selected from the International Collaboration on Endocarditis Merged Database (ICE-MD) if they underwent TEE. Among 311 patients who had definite aortic valve IE, 67 (22%) had periannular abscesses. They were more likely to have infection in the setting of a prosthetic valve (40% vs 19%, p <0.001) and coagulase-negative staphylococcal IE (18% vs 6%, p < 0.01) and less likely to have streptococcal IE than were patients who did not develop abscess (28% vs 46%, p = 0.01). Systemic embolization, central nervous system events, and heart failure did not differ between those who developed abscess and those who did not, but power was limited. Patients who had abscess were more likely to undergo surgery (84% vs 36%, p <0.001), and their in-hospital mortality rate was higher (19% vs 11%, p = 0.09). Multivariate analysis of prognostic factors of mortality in aortic IE identified age (odds ratio [OR] 1.6, 95% confidence interval [CI]1.2 to 2.1), Staphylococcus aureus (S. aureus) infection (OR 2.4, 95% CI 1.1 to 5.2), and heart failure (OR 2.9, 95% CI 1.4 to 6.1) as variables that were independently associated with increased risk of death. Periannular abscess formation showed a nonsignificant trend toward an increased risk of death (OR 1.9, 95% CI 0.9 to 3.8). Multivariate analysis of prognostic factors of mortality in complicated aortic IE with abscess formation identified S. aureus infection (OR 6.9, 95% CI 1.6 to 29.4) as independently associated with increased risk of death. In conclusion, in the current era of TEE and high use of surgical treatment, periannular abscess formation in aortic valve IE is not an independent risk factor for mortality. S. aureus infection is an independent prognostic factor for mortality in patients who have abscess formation.The American Journal of Cardiology 10/2005; 96(7):976-81. · 3.37 Impact Factor -
Article: Tick-borne disease.
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ABSTRACT: Tick-borne diseases in the United States include Rocky Mountain spotted fever, Lyme disease, ehrlichiosis, tularemia, babesiosis, Colorado tick fever, and relapsing fever. It is important for family physicians to consider these illnesses when patients present with influenza-like symptoms. A petechial rash initially affecting the palms and soles of the feet is associated with Rocky Mountain spotted fever, whereas erythema migrans (annular macule with central clearing) is associated with Lyme disease. Various other rashes or skin lesions accompanied by fever and influenza-like illness also may signal the presence of a tick-borne disease. Early, accurate diagnosis allows treatment that may help prevent significant morbidity and possible mortality. Because 24 to 48 hours of attachment to the host are required for infection to occur, early removal can help prevent disease. Treatment with doxycycline or tetracycline is indicated for Rocky Mountain spotted fever, Lyme disease, ehrlichiosis, and relapsing fever. In patients with clinical findings suggestive of tick-borne disease, treatment should not be delayed for laboratory confirmation. If no symptoms follow exposure to tick bites, empiric treatment is not indicated. The same tick may harbor different infectious pathogens and transmit several with one bite. Advising patients about prevention of tick bites, especially in the summer months, may help prevent exposure to dangerous vector-borne diseases.American family physician 07/2005; 71(12):2323-30. · 1.70 Impact Factor
Top co-authors
Top Journals
Institutions
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2011
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Duke University
- Department of Biostatistics and Bioinformatics
Durham, NC, USA
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2005
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University of Barcelona
Barcelona, Catalonia, Spain -
Mayo Clinic - Scottsdale
Scottsdale, AZ, USA
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