Implementation of a data control framework to ensure confidentiality, integrity, and availability of high-quality real-world data (RWD) in the NeuroTransData (NTD) registry.

Objective: To implement a dynamic data management and control framework that meets the multiple demands of high data quality, rigorous information technology security, and flexibility to continuously incorporate new methodology for a large disease registry.

Materials And Methods: Guided by relevant sections of the COBIT framework and ISO 27001 standard, we created a data control framework supporting high-quality real-world data (RWD) studies in multiple disease areas. We first mapped and described the entire data journey and identified potential risks for data loss or inconsistencies.

Proof-of-concept study: Homomorphically encrypted data can support real-time learning in personalized cancer medicine.

Background: The successful introduction of homomorphic encryption (HE) in clinical research holds promise for improving acceptance of data-sharing protocols, increasing sample sizes, and accelerating learning from real-world data (RWD). A well-scoped use case for HE would pave the way for more widespread adoption in healthcare applications. Determining the efficacy of targeted cancer treatments used off-label for a variety of genetically defined conditions is an excellent candidate for introduction of HE-based learning systems because of a significant unmet need to share and combine confidential data, the use of relatively simple algorithms, and an opportunity to reach large numbers of willing study participants.

Approving cancer treatments based on endpoints other than overall survival: an analysis of historical data using the PACE Continuous Innovation Indicators™ (CII).

Background: There is an active debate about the role that endpoints other than overall survival (OS) should play in the drug approval process. Yet the term 'surrogate endpoint' implies that OS is the only critical metric for regulatory approval of cancer treatments. We systematically analyzed the relationship between U.

Dynamic value assessments in oncology supported by the PACE Continuous Innovation Indicators.

Aim: Several recently developed frameworks aim to assess the value of cancer treatments, but the most appropriate metrics remain uncertain.

Methods: We use data from the Patient Access to Cancer care Excellence Continuous Innovation Indicators to examine the relationship between hazard ratios (HRs) from clinical trials and dynamic therapeutic value accumulating over time.

Results: Our analysis shows that HRs from initial clinical trials poorly predict the eventual therapeutic value of cancer treatments.

ReMo-SNPs: a new software tool for identification of polymorphisms in regions and motifs genome-wide.

Studies of complex genetic diseases have revealed many risk factors of small effect, but the combined amount of heritability explained is still low. Genome-wide association studies are often underpowered to identify true effects because of the very large number of parallel tests. There is, therefore, a great need to generate data sets that are enriched for those markers that have an increased a priori chance of being functional, such as markers in genomic regions involved in gene regulation.

PACE Continuous Innovation Indicators-a novel tool to measure progress in cancer treatments.

Concerns about rising health care costs and the often incremental nature of improvements in health outcomes continue to fuel intense debates about 'progress' and 'value' in cancer research. In times of tightening fiscal constraints, it is increasingly important for patients and their representatives to define what constitutes 'value' to them. It is clear that diverse stakeholders have different priorities.

Association of a protective paraoxonase 1 (PON1) polymorphism in Parkinson's disease.

Pesticide exposure has been suggested to increase the risk to develop Parkinson's disease (PD). The arylesterase paraoxonase 1 (PON1) is mainly expressed in the liver and hydrolyzes organophosphates such as pesticides. The polymorphism Leu54Met (rs854560) in PON1, impairing enzyme activity and leading to decreased PON1 expression levels, has been reported to be associated with Parkinson's disease (PD).

Significant association of estrogen receptor binding site variation with bipolar disorder in females.

Major depression is nearly twice as prevalent in women compared to men. In bipolar disorder, depressive episodes have been reported to be more common amongst female patients. Furthermore, periods of depression often correlate with periods of hormonal fluctuations.

MAGI1 copy number variation in bipolar affective disorder and schizophrenia.

Background: Bipolar affective disorder (BPAD) and schizophrenia (SZ) are devastating psychiatric disorders that each affect about 1% of the population worldwide. Identification of new drug targets is an important step toward better treatment of these poorly understood diseases.

Methods: Genome-wide copy number variation (CNV) was assessed and variants were ranked by co-occurrence with disease in 48 BPAD families.

The FKBP5-gene in depression and treatment response--an association study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort.

Background: In a recent study of several antidepressant drugs in hospitalized, non-Hispanic White patients, Binder et al. reported association of markers located within the FKBP5 gene with treatment response after 2 and 5 weeks. Individuals homozygous for the TT-genotype at one of the markers (rs1360780) reported more depressive episodes and responded better to antidepressant treatment.

Association of GRIK4 with outcome of antidepressant treatment in the STAR*D cohort.

Objective: An initial pharmacogenetic study of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) clinical trial reported an association between genetic variation in the HTR2A gene and outcome of citalopram treatment. By design, the study analyzed only those markers that showed reproducible association in the first wave of genotypes (comprising 1,297 patients) in the complete cohort of patients. The purpose of the present study was to utilize a second wave of genotype results, for a more powerful analysis, in the complete cohort of patients with available deoxyribonucleic acid (DNA) samples.

Association between a functional serotonin transporter promoter polymorphism and citalopram treatment in adult outpatients with major depression.

Context: The HTTLPR, a functional polymorphism of the serotonin transporter gene solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4), promoter, affects transcription and may be involved in antidepressant drug treatment outcome, although response rates with antidepressants can be lower in patients who experience adverse effects.

Objective: To test the hypothesis that HTTLPR is associated with treatment outcome to citalopram.

Design: A clinical effectiveness trial, Sequenced Treatment Alternatives to Relieve Depression, collected DNA samples from outpatients with nonpsychotic major depressive disorder who received citalopram in the first treatment step.