Evaluation of increased adherence and cost savings of an employer value-based benefits program targeting generic antihyperlipidemic and antidiabetic medications.

BACKGROUND: A major employer implemented a change to its employee health benefits program to allow beneficiaries with diabetes or high cholesterol to obtain preselected generic antidiabetic or generic antihyperlipidemic medications with a zero dollar copayment. To receive this benefit, plan beneficiaries were required to participate in a contracted vendor's case management and/or wellness program.  OBJECTIVE: To assess changes in medication adherence and the costs for generic antidiabetic and generic antihyperlipidemic medications resulting from participation in a zero copay (ZCP) program.   METHODS: This was a retrospective pre-post comparison group study, evaluating adherence and cost. Participants using an antihyperlipidemic and/or antidiabetic medication during the study identification period and post-implementation period for the program were considered eligible for the study. Eligible beneficiaries who enrolled in the ZCP program during the post-implementation period were considered participants, while those who did not enroll during this period were considered nonparticipants. ZCP program participants and nonparticipants were matched via a 1-to-1 propensity scoring method using age, gender, comorbidity count, medication type (antihyperlipidemic, antidiabetic, or both), and baseline adherence as matching criteria. The proportion of days covered (PDC) metric expressed as a mean percentage was used to assess adherence to medication therapy, while payer cost was examined using prescription drug utilization expressed as per member per year (PMPY) and cost change per 30 days of medication expressed in dollars.   RESULTS: Among participants who were users of antidiabetic medications, the mean adherence rate was sustained from pre- to post-implementation (81.8% vs. 81.9%); however, it decreased in the matched nonparticipant group (81.9% vs. 73.1%). This difference in mean adherence over time between the participants and nonparticipants was statistically significant (0.1% vs. -8.8%, P less than 0.001). Similar results were found among users of antihyperlipidemics. The mean adherence rate was sustained over time for participants (77.7% vs. 78.3%) but declined over time for nonparticipants (77.6% vs. 70.8%). The difference in mean change over time was statistically significant between participants and nonparticipants (0.6% vs. -6,8%, P less than 0.001). Average prescription costs PMPY increased for participants of the ZCP program during the post-implementation period; however, the increase was not larger than the cost increase among nonparticipants ($581 vs. $584, P = 0.95). Furthermore, among antihyperlipidemics the cost increase post-implementation was actually significantly less for participants than nonparticipants ($51 vs. $143, P less than 0.001).  CONCLUSIONS: Plan sponsors are increasingly evaluating the use of value-based benefit design (VBBD) to change member behavior. This ZCP program used a reduction in cost sharing to incentivize members to use more generic drugs and to enroll in a care management coaching program. The study also demonstrated that a VBBD program can have a positive impact on adherence and cost outcomes among those who participate compared with nonparticipants. 

Improved Agrobacterium-mediated transformation of three maize inbred lines using MS salts.

Transformation technology as a research or breeding tool to improve maize is routinely used in most industrial and some specialized public laboratories. However, transformation of many inbred lines remains a challenging task, especially when using Agrobacterium tumefaciens as the delivery method. Here we report success in generating transgenic plants and progeny from three maize inbred lines using an Agrobacterium-mediated standard binary vector system to target maize immature embryos. Eleven maize inbred lines were pre-screened for transformation frequency using N6 salts. A subset of three maize inbred lines was then systematically evaluated for frequency of post-infection embryogenic callus induction and transformation on four media regimes: N6 or MS salts in each of two distinct media backgrounds. Transgenic plants recovered from inbred lines B104, B114, and Ky21 were analyzed for transgene integration, expression, and transmission. Average transformation frequencies of 6.4% (for B104), 2.8% (for B114), and 8% (for Ky21) were achieved using MS salts. Availability of Agrobacterium-mediated maize inbred line transformation will improve future opportunities for maize genetic and functional genomic studies.

A functional antigen in a practical crop: LT-B producing maize protects mice against Escherichia coli heat labile enterotoxin (LT) and cholera toxin (CT).

We have produced a functional heat labile enterotoxin (LT-) B subunit of Escherichia coli in maize. LT-B is a multimeric protein that presents an ideal model for an edible vaccine, displaying stability in the gut and inducing mucosal and systemic immune responses. Transgenic maize was engineered to synthesize the LT-B polypeptides, which assembled into oligomeric structures with affinity for G(M1) gangliosides. We orally immunized BALB/c mice by feeding transgenic maize meal expressing LT-B or non-transgenic maize meal spiked with bacterial LT-B. Both treatments stimulated elevated IgA and IgG antibodies against LT-B and the closely related cholera toxin B subunit (CT-B) in serum, and elevated IgA in fecal pellets. The transgenic maize induced a higher anti-LT-B and anti-CT-B mucosal and serum IgA response compared to the equivalent amount of bacterial LT-B spiked into maize. Following challenge by oral administration of the diarrhea inducing toxins LT and CT, transgenic maize-fed mice displayed reduced fluid accumulation in the gut compared to non-immunized mice. Moreover, the gut to carcass ratio of immunized mice was not significantly different from the PBS (non-toxin) challenged control group. We concluded that maize-synthesized LT-B had features of the native bacterial LT-B such as molecular weight, G(M1) binding ability, and induction of serum and mucosal immunity. We have demonstrated that maize, a major food and feed ingredient, can be efficiently transformed to produce, accumulate, and store a fully assembled and functional candidate vaccine antigen.