Inaugural Pharmacogenomics Access and Reimbursement Symposium.

The Pharmacogenomics Access & Reimbursement Symposium, a landmark event presented by the Golden Helix Foundation and the Pharmacogenomics Access & Reimbursement Coalition, was a 1-day interactive meeting comprised of plenary keynotes from thought leaders across healthcare that focused on value-based strategies to improve patient access to personalized medicine. Stakeholders including patients, healthcare providers, industry, government agencies, payer organizations, health systems and health policy organizations convened to define opportunities to improve patient access to personalized medicine through best practices, successful reimbursement models, high quality economic evaluations and strategic alignment. Session topics included health technology assessment, health economics, health policy and value-based payment models and innovation.

PARC report: a health-systems focus on reimbursement and patient access to pharmacogenomics testing.

Pharmacogenomics test coverage and reimbursement are major obstacles to clinical uptake. Several early adopter programs have been successfully initiated through dedicated investments by federal and institutional research funding. As a result of research endeavors, evidence has grown sufficiently to support development of pharmacogenomics guidelines. However, clinical uptake is still limited. Third-party payer support plays an important role in increasing adoption, which to date has been limited to reactive single-gene testing. Access to and interest in direct-to-consumer genetic testing are driving demand for increasing healthcare providers and third-party awareness of this burgeoning field. Pharmacogenomics implementation models developed by early adopters promise to expand patient access and options, as testing continues to increase due to growing consumer interest and falling test prices.

PARC report: a perspective on the state of clinical pharmacogenomics testing.

In this Perspective, the authors discuss the state of pharmacogenomics testing addressing a number of advances, challenges and barriers, including legal ramifications, changes to the regulatory landscape, coverage of testing and the implications of direct-to-consumer genetic testing on the provision of care to patients. Patient attitudes toward pharmacogenomics testing and associated costs will play an increasingly important role in test acquisition and subsequent utilization in a clinical setting. Additional key steps needed include: further research trials demonstrating clinical utility and cost-effectiveness of pharmacogenetic testing, evidence review to better integrate genomic information into clinical practice guidelines in target therapeutic areas to help providers identify patients that may benefit from pharmacogenetic testing and engagement with payers to create a path to reimbursement for pharmacogenetic tests that currently have sufficient evidence of clinical utility. Increased adoption of testing by payers and improved reimbursement practices will be needed to overcome barriers, especially as the healthcare landscape continues to shift toward a system of value-based care.

An Educational Board Game to Assist PharmD Students in Learning Autonomic Nervous System Pharmacology.

Objective. To examine whether playing a board game can assist PharmD students in learning autonomic nervous system (ANS) pharmacology. Design. Of 72 students enrolled in a required second-year pharmacology course, 22 students volunteered to play the board game, which was followed by an in-class examination consisting of 42 ANS questions (ANSQs) and 8 control questions (CTLQs). Participants were given a pretest and a posttest to assess immediate educational improvement. Participants' scores for pretest, posttest, in-class examination, and ANSQs were compared. Also, scores for examination, ANSQs, and CTLQs were compared between board game participants (PART) and nonparticipating classmates (NPART). Assessment. Board game participants scored progressively higher between the pretest, posttest, examination, and ANSQs. Additionally, PART scores were higher than NPART scores for examination and ANSQs. Difference between PART and NPART CTLQ scores was not significant. Conclusion. A board game can assist PharmD students in learning ANS pharmacology.

Association between Aurora-A kinase polymorphisms and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population.

Aurora-A kinase is considered a potential cancer susceptibility gene that encodes a centrosome-associated, cell cycle-regulated serine/threonine kinase. We studied two single nucleotide polymorphisms (SNP) in the coding region of Aurora-A, 91T-to-A (F31I) and 169G-to-A (V57I). We studied the influence of these two polymorphisms on age of onset of hereditary nonpolyposis colorectal cancer (HNPCC). Genotyping of the Aurora-A polymorphisms was carried out on 125 Caucasian with mismatch repair (MMR) gene mutations with real-time pyrophosphate DNA sequencing. For the 91T-to-A polymorphism, we found that patients with HNPCC who were homozygous for the wild-type allele developed colorectal cancer (CRC) 7 years earlier than patients who were homozygous or heterozygous for the mutant allele. The169G-to-A polymorphism did not have a significant influence on risk for HNPCC. However, when we did haplotype analysis for these two polymorphisms, the 91A-169G haplotype was associated with protection from HNPCC at an earlier age.

DNMT3b polymorphism and hereditary nonpolyposis colorectal cancer age of onset.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome of familial malignancies resulting from germ-line mutations in DNA mismatch repair genes. Colorectal and endometrial cancers are most frequently observed. A polymorphic C-to-T change in the promoter region of the DNMT3b gene, -149 bp from the transcription start site, is reported to greatly increase promoter activity and is associated with increased risk for lung cancer and decreased postsurgical survival in patients with small cell carcinoma of the head and neck. We studied the influence of this DNMT3b polymorphism on HNPCC age of onset. We determined the DNMT3b genotype of 146 mismatch repair mutation carriers from 72 families. Of these, 74 participants had colorectal cancer. The participants were genotyped by single-strand conformational polymorphism analysis and DNA sequencing. We tested the association between age of onset and DNMT3b genotypes by comparing Kaplan-Meier survival curves, evaluating the homogeneity of the curves using the log-rank test, Wilcoxon's test, and Fleming-Harrington test and estimating the strength and direction of the association using the Cox proportional hazards regression model adjusting for potential demographic and genetic confounding factors. HNPCC patients carrying one or two copies of the DNMT3b variant T allele developed their colorectal cancer significantly earlier than HNPCC patients who were homozygous for the wild-type DNMT3b allele. Combining knowledge of an individual's DNMT3b genotype with information on other genetic and environmental risk factors may improve risk estimates and help to identify individuals who are genetically susceptible to developing HNPCC at an earlier age.

IGF1 gene polymorphism and risk for hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) genes. Insulin-like growth factor-I (IGF-I) is involved in colorectal carcinogenesis, and elevated plasma IGF-I levels are associated with sporadic colorectal cancer (CRC) risk. We investigated the relationship between IGF1 promoter cytosine-adenine (CA) dinucleotide-repeat polymorphism length and CRC risk in 121 MMR gene mutation carriers using Cox regression and Kaplan-Meier analysis. All statistical tests were two-sided. Time to onset for CRC increased for each decrease in CA-repeat number (median = 19 repeats, range = 12-22 repeats; hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.05 to 1.31; P = .006). Patients carrying a CA(< or = 17) repeat allele had a statistically significantly higher CRC risk (HR = 2.36; 95% CI = 1.28 to 4.36; P = .006) than all others and were younger at onset (44 years versus 56.5 years; P = .023). These findings indicate a statistically significant association between shorter IGF1 CA-repeat lengths and increased risk for CRC in HNPCC. This is the first report, to our knowledge, to show that IGF1 variant genotypes modify risk of a hereditary form of cancer.

ATM polymorphism and hereditary nonpolyposis colorectal cancer (HNPCC) age of onset (United States).

OBJECTIVE: We examined a G-to-A single nucleotide polymorphism of the ATM gene, to determine if it influences hereditary non-polyposis colorectal cancer (HNPCC) age of onset. HNPCC is caused by mutations in mismatch repair genes, especially hMLH1 and hMSH2. ATM germline mutations have been associated with breast and digestive cancers. In a smaller European study, the G-to-A polymorphism was associated with an increased risk of developing an HNPCC-related cancer within HNPCC families. MATERIALS AND METHODS: We genotyped 109 mismatch repair gene (MMR) mutation carriers from 53 HNPCC families for the ATM polymorphism using PCR and single strand conformational polymorphism (SSCP) analysis. We tested the association between the ATM genotypes and HNPCC age of onset by survival analysis. RESULTS: The ATM polymorphism did not significantly modify HNPCC age of onset, nor overall risk, in our population. CONCLUSIONS: Although a modifier effect was not seen in our study, future studies that examine the polymorphism in combination with other genetic and environmental factors may elucidate an association. Revealing such associations in MMR mutation carriers may improve risk estimates and help to identify individuals who are genetically susceptible to developing HNPCC at an earlier age.

p53 polymorphism and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population.

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant syndrome of familial malignancies. Colorectal and endometrial cancers are most frequently observed. The syndrome results mainly from germ-line mutations in DNA mismatch repair genes. A common G-to-C polymorphism at codon 72 in the p53 gene has been associated with increased risk for lung, nasopharyngeal, oral, prostate, and breast cancers and may be a marker for genetic susceptibility to colorectal cancer. We studied the influence of this p53 polymorphism on HNPCC age of onset. EXPERIMENTAL DESIGN: We determined the p53 genotype of 92 Caucasian mismatch repair mutation carriers, of which, 47 had colorectal cancer. The subjects were genotyped by single-strand conformational polymorphism analysis. We tested the association between age of onset and the p53 genotypes by comparing Kaplan-Meier survival curves, evaluating the homogeneity of the curves using the log-rank test and Wilcoxon's test, and estimating the association using the Cox proportional hazards regression model to adjust for potential demographic confounding factors. RESULTS: The HNPCC patients who were heterozygous developed their colorectal cancer 13 years earlier than HNPCC patients who were homozygous for the wild-type allele. CONCLUSIONS: Combining knowledge of an individual's p53 genotype with information on other genetic and environmental risk factors may improve risk estimates and help to identify individuals who are genetically susceptible to developing HNPCC at an earlier age.