Influence of MedDRA hierarchy on pharmacovigilance data mining results
IJMI Volume 78, Issue 12, Pages e97-e103 (December 2009)
Use of HLT and SMQ groupings can improve the percentage of unlabeled supported SDRs in data mining results. The trade-off for this gain is the medically less-specific language of HLTs and SMQs compared to PTs, and the need for the added step in data mining of examining the component PTs of each HLT or SMQ that results in a signal of disproportionate reporting.

Performance of a Semi-Automated Process for Estimation of Risk using Observational Databases
Poster Presentation at ICPE 2009 Annual Meeting in Providence, RI

Background
Proactive safety surveillance is anticipated to generate many new potential drug safety signals. SÆfetyWorks^® v2.3 (SW), a semi-automated application using large observational databases, generates an incidence rate ratio (IRR) and 95% confidence interval (CI) for potential associations between a drug and a medical condition derived from a retrospective cohort design ("risk estimation"). SW allows users to select parameters important to statistical modeling design and suggests covariates for propensity score (PS) modeling and confounders for Poisson regression.

Objectives
To evaluate the performance of SW by replicating published studies using retrospective cohort or case-control designs to address drug and medical condition associations and comparing the IRR and CI generated by SW to the results in the respective published study.

Performance of Screening Multiple Observational Databases for Active Drug Safety Surveillance
Poster Presentation at ICPE 2009 Annual Meeting in Providence, RI

Background
Recent calls have been made to establish a national active drug safety surveillance system that leverages observational data, including administrative claims and electronic health records, to monitor and evaluate potential safety issues of medicines. Several initiatives aim to inform efforts in this area. However, the development and evaluation of appropriate statistical methods for observational data have not yet been comprehensively studied to assess the impact on current pharmacovigilance practice.

Objective
To evaluate the performance of alternative screening methods for identifying drug-condition associations across two disparate observational databases.

Risk Estimation Analytical Methods
White Paper
This document describes risk estimation, the underlying method used in SAEfetyWorks to calculate an Incidence Rate Ratio (IRR) which compares the rates of a particular adverse event between two drugs, known as the target and the comparator. Some statistics associated with the IRR, such as confidence limits, are also computed. Propensity score adjustment is employed to minimize the impact of confounding clinical and demographic factors on the calculated IRR.

Drug-versus-Drug Adverse Event Rate Comparisons: A Pilot Study Based on Data from the US FDA Adverse Event Reporting System
Drug Safety 2009, Volume 32, Issue 2
A number of published studies compare adverse event rates for drugs on the basis of reports in the US FDA Adverse Event Reporting System (AERS). While the AERS data have the advantage of timely availability and a large capture population, the database is subject to many significant biases and lacks complete patient information that would allow for correction of those biases.

Abstract

Exenatide and pancreatitis: the importance of reporting negative findings in data mining
Pharmaceutical Medicine (2008; 22(4): 215-219)
The US Food and Drug Administration (FDA) recently published a warning regarding pancreatitis in association with the use of exenatide, an incretin mimetic used for the treatment of patients with diabetes mellitus. We note that this safety issue is not associated with a signal of disproportionate reporting (SDR) in the FDA Adverse Event Reporting System (AERS) database or the World Health Organization (Uppsala Monitoring Centre) Vigibase for any of four data-mining algorithms we tested (proportional reporting ratio, the multi-item gamma-Poisson shrinker, an urn model and the Bayesian Confidence Propagation Neural Network). Exenatide and acute pancreatitis may thus represent a ‘false-negative’ result for disproportionality-based data-mining methodology generally. We evaluate the possibility that this lack of an SDR is caused by the phenomenon known as ‘masking’ (or ‘cloaking’) and reject this hypothesis. While positive findings are understandably more exciting, we discuss why publishing negative findings, such as in this example, is important for placing the capabilities and limitations of drug safety data mining into proper perspective.

Using Data Mining to Predict Safety Actions from FDA Adverse Event Reporting System Data
Drug Information Journal (September, 2007)
Using AERS data 2-3 years following approval, more than half of FDA actions that aoccurred in the next 2-4 years were predicted by data mining, and more than half of the signals detected by data mining corresponded to an FDA action. An appropriate data mining procedure can yield meaningful safety information, often well in advance of regulatory action.

Data Mining in Pharmacovigilance
International Journal of Pharmaceutical Medicine (September, 2007)
This commentary discusses aspects of computational intensity and cost associated with the application of data mining algorithms (DMAs) to spontaneous reporting system data and inllustrate these wiht a reported drug-event association that was the subject of a recent publication in the journal Drug Safety.

Scientific Software Development is not an Oxymoron
PLOS Computational Biology(9/8/2006)
We see important similarities between the way scientists and software engineers approach and attack problems which may provide a general framework for successful scientific software development. Scientists are taught the scientific method from the time they perform their first experiments. Similarly, software engineers are taught about the software development life cycle before they write their first “if” statement. By understanding similarities between these approaches, we can layer some practical methods from the software development life cycle onto computational biology projects to build a solid foundation for success.

Mycophenolate Mofetil Use is Associated with Decreased Risk of Late Acute Rejection in Adult Liver Transplant Recipients
American Journal of Transplantation (March 2006)
Mycophenolate mofetil (MMF) used in a triple-drug regimen has been shown to decrease acute rejection rates, compared to a double-drug regimen. The impact of MMF on late acute rejection (LAR) episodes has not been well described.

Switching Immunosuppression Medications After Renal Transplantation, A Common Practice
Nephrology Dialysis Transplantation (March 2006)
The rate of change to immunosuppression discharge regimens over time is unknown. We examined the frequency of changes to initial drug treatment regimens and factors associated with a drug change following renal transplantation.

Addition of MMF to Dual Immunosuppression Does Not Increase the Risk of Malignant Short-Term Death After Liver Transplantation
American Journal of Transplantation (Volume 5 Page 2961 - December 2005)
Immunosuppression is often incriminated for the increased risk of post-transplant malignancies. To examine whether triple- (MMF+Tacro+CS) versus dual-drug therapy (Tacro+CS) is associated with an increased incidence of malignancy, or death due to malignancy, data from a large registry of liver transplant recipients were analyzed.

Effectiveness of Amphotericin B Lipid Complex (ABLC) Treatment in Allogeneic Hematopoietic Cell Transplant (HCT) Recipients with Invasive Aspergillosis (IA)
Bone Marrow Transplantation (November 2005 Volume 36 873–877)
These data suggest that ABLC, especially when administered as first-line therapy, can result in clinical response even in the most immunocompromised patients, that is, HCT recipients with GVHD, with minimal effects on renal function.

Clinical Experience with Non-Standard Doses of Alpha Interferon and Ribavirin in the Treatment of Chronic Hepatitis C Infection: A Retrospective Analysis
Current Therapeutic Research (September/October 2005, Volume 66 Number 5, 433-450)

Comparison of Characteristics of Treated and Non-Treated Patients with Hepatitis C Infection
Pharmacoepidemiology and Drug Safety (September 2005 Volume 15 Issue 2 71-76)
This study suggests that it is not the clinical stage of HCV infection but the patient's demographic characteristics and co-morbid conditions that impact the decision to initiate HCV therapy.

Disease Progression Modeling from Historical Clinical Databases
11th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining (Chicago, August 2005)
Applies a stepwise clustering procedure to stratify liver transplant patients into groups with distinct survival characteristics for survival prediction using a database from the National Institute of Diabetes and Digestive and Kidney Diseases

Mycophenolate Mofetil Combination Therapy Improves Long-Term Outcomes After Liver Transportation in Patients With and Without Hepatitis C
Liver Transplantation (July 2005 750-759)

Daclizumab is Associated with Decreased Rejection and Improved Patient Survival in Renal Transplant Recipients
Clinical Transplantation (June 2005 Volume 19 Issue 3 340-345)

Treatment of Candida Infections with Amphotericin B Lipid Complex
Clinical Infectious Diseases (May 2005;40:S384-S391)
This study investigates the renal safety and efficacy of intravenous ABLC in treating patients infected with both invasive and noninvasive C. albicans and non-albicans Candida species. In addition, observations with regard to response rates by primary underlying condition, azole combination therapy, and neutrophil status are described.

Use of Amphotericin B Lipid Complex in Elderly Patients
Journal of Infection (May 2005 Volume 50 Issue 4 277-287)
The safety and effectiveness of amphotericin B lipid complex (ABLC) treatment in elderly patients was investigated using a large multicenter database and suggests that ABLC can be safely and effectively used in the treatment of invasive fungal disease in elderly patients.

Mycophenolate Mofetil versus Azathioprine is Associated with Decreased Cardiovascular Death and Decreased Rejection in Renal Transplant Recipients with Pre-Transplant Diabetes
Clinical Transplantation (April 2005 Volume 19 Issue 2 Page 279)
Outcomes specifically in mycophenolate mofetil (MMF)-treated diabetic renal transplant patients have not been previously reported. This study compared acute rejection (AR), late acute rejection (LAR), patient survival [and specifically death from cardiovascular (CV), infectious and malignant causes], incidence of post-transplant malignancies, and graft loss in MMF- or azathioprine (AZA)-treated renal transplant patients with pre-transplant diabetes.

Daclizumab is associated with decreased rejection and no increased mortality in cardiac transplant patients receiving MMF, cyclosporine, and corticosteroids
Transplantation Proceedings (March 2005 Volume 37 Issue 2 1333-1339 )
Sparse published data exist on outcomes in daclizumab-treated cardiac transplant patients. One trial observed an increased mortality risk 6 and 12 months posttransplant in patients receiving daclizumab plus mycophenolate mofetil (MMF), cyclosporine, and steroids. This study further investigates the safety profile of daclizumab with this same immunosuppressive regimen from a large registry.

Differential Effects of Donor Age in Liver Transplant Recipients Infected with Hepatitis B, Hepatitis C, and Without Viral Hepatitis
American Journal of Transplantation (March 2005 Volume 5 Issue 3 Page 549)
The variable impact of specific risk factors on survival outcomes based on pre-transplantation diagnosis was analyzed in adult liver transplant recipients reported to the Scientific Registry of Transplant Recipients: 778 with hepatitis B (HBV), 3463 with hepatitis C (HCV) and 7429 without viral hepatitis.

Intensive Lifestyle Modification: Impact on Cardiovascular Disease Risk Factors in Subjects With and Without Clinical Cardiovascular Disease.
Preventive Cardiology (2004 Fall;7(4):168-75.)
Results of a study conducted by ProSanos with Windber Research Institute. The findings suggest that intensive lifestyle change programs may be important for primary prevention in individuals at increased risk of cardiovascular disease.

Mycophenolate Mofetil versus Azathioprine in a Large Population of Elderly Renal Transplant Patients
Nephrology Dialysis Transplantation (November 2004 Volume 19 2864-2869)
Mycophenolate mofetil (MMF) has been shown to decrease acute rejection episodes after kidney transplantation, and has been associated with better graft and patient survival vs azathioprine (AZA). Previous studies reported a higher risk of death due to infection in elderly recipients treated with MMF-based immunosuppression.

Retrospective Study of the Renal Effects of Amphotericin B Complex When Used at Higher-Than-Recommended Dosages and Longer Durations Compared with Lower Dosages and Shorter Durations in Patients with Systemic Fungal Infections
Clinical Therapeutics (October 2004 Volume 26 Issue 10 1652-1662 )
Patients with fungal infections who are treated with amphotericin B lipid complex (ABLC) often receive dosages less than that recommended in the product information (5 mg/kg·d). This occurs despite the described safety and increased efficacy in select patients treated with higher ABLC dosages and suggests that higher ABLC dosages appear to be as well tolerated as lower dosages, warrantingfurther study of ABLC dosages >5 mg/kg·d for >12 days in the treatment of systemic fungal infections.

Sirolimus with Neoral Versus Mycophenolate Mofetil with Neoral is Associated with Decreased Renal Allograft Survival
American Journal of Transplantation (Accepted for publication; in press)
Read the abstract of an article expected to be published in December or January.

Mycophenolate Mofetil Versus Azathioprine Therapy is Associated with a Significant Protection Against Long-term Renal Allograft Function Deterioration
Transplantation (Volume 75, Issue 8, April 27, 2003)
An article published in the official journal of the Transplantation Society, reporting further results of studies conducted by ProSanos for Hoffman-La Roche.

Long-term Use of Mycophenolate Mofetil is Associated with a Reduction in the Incidence and Risk of Late Rejection
American Journal of Transplantation
(Volume 3, Issue 1, January 2003)
An article in the official journal of the American Society of Transplant Surgeons and the American Society of Transplantation, reporting in detail selected results of the first study conducted by ProSanos for Hoffman-La Roche.