Pharmaceutical policies: effects of reference pricing, other pricing, and purchasing policies.

BACKGROUND: Pharmaceuticals are important interventions that could improve people's health. Pharmaceutical pricing and purchasing policies are used as cost-containment measures to determine or affect the prices that are paid for drugs. Internal reference pricing establishes a benchmark or reference price within a country which is the maximum level of reimbursement for a group of drugs. Other policies include price controls, maximum prices, index pricing, price negotiations and volume-based pricing. OBJECTIVES: To determine the effects of pharmaceutical pricing and purchasing policies on health outcomes, healthcare utilisation, drug expenditures and drug use. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), part of The Cochrane Library (including the Effective Practice and Organisation of Care Group Register) (searched 22/10/2012); MEDLINE In-Process & Other Non-Indexed Citations and MEDLINE, Ovid (searched 22/10/2012); EconLit, ProQuest (searched 22/10/2012); PAIS International, ProQuest (searched 22/10/2012); World Wide Political Science Abstracts, ProQuest (searched 22/10/2012); INRUD Bibliography (searched 22/10/2012); Embase, Ovid (searched 14/12/2010); NHSEED, part of The Cochrane Library (searched 08/12/2010); LILACS, VHL (searched 14/12/2010); International Political Science Abstracts (IPSA), Ebsco (searched (17/12/2010); OpenSIGLE (searched 21/12/10); WHOLIS, WHO (searched 17/12/2010); World Bank (Documents and Reports) (searched 21/12/2010); Jolis (searched 09/10/2011); Global Jolis (searched 09/10/2011) ; OECD (searched 30/08/2005); OECD iLibrary (searched 30/08/2005); World Bank eLibrary (searched 21/12/2010); WHO - The Essential Drugs and Medicines web site (browsed 21/12/2010). SELECTION CRITERIA: Policies in this review were defined as laws; rules; financial and administrative orders made by governments, non-government organisations or private insurers. To be included a study had to include an objective measure of at least one of the following outcomes: drug use, healthcare utilisation and health outcomes or costs (expenditures); the study had to be a randomised trial, non-randomised trial, interrupted time series (ITS), repeated measures (RM) study or a controlled before-after study of a pharmaceutical pricing or purchasing policy for a large jurisdiction or system of care. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias. Results were summarised in tables. There were too few comparisons with similar outcomes across studies to allow for meta-analysis or meaningful exploration of heterogeneity. MAIN RESULTS: We included 18 studies (seven identified in the update): 17 of reference pricing, one of which also assessed maximum prices, and one of index pricing. None of the studies were trials. All included studies used ITS or RM analyses. The quality of the evidence was low or very low for all outcomes. Three reference pricing studies reported cumulative drug expenditures at one year after the transition period. Two studies reported the median relative insurer's cumulative expenditures, on both reference drugs and cost share drugs, of -18%, ranging from -36% to 3%. The third study reported relative insurer's cumulative expenditures on total market of -1.5%. Four reference pricing studies reported median relative insurer's expenditures on both reference drugs and cost share drugs of -10%, ranging from -53% to 4% at one year after the transition period. Four reference pricing studies reported a median relative change of 15% in reference drugs prescriptions at one year (range -14% to 166%). Three reference pricing studies reported a median relative change of -39% in cost share drugs prescriptions at one year (range -87% to -17%). One study of index pricing reported a relative change of 55% (95% CI 11% to 98%) in the use of generic drugs and -43% relative change (95% CI -67% to -18%) in brand drugs at six months after the transition period. The same study reported a price change of -5.3% and -1.1% for generic and brand drugs respectively six months after the start of the policy. One study of maximum prices reported a relative change in monthly sales volume of all statins of 21% (95% CI 19% to 24%) after one year of the introduction of this policy. Four studies reported effects on mortality and healthcare utilisation, however they were excluded because of study design limitations. AUTHORS' CONCLUSIONS: The majority of the studies of pricing and purchasing policies that met our inclusion criteria evaluated reference pricing. We found that internal reference pricing may reduce expenditures in the short term by shifting drug use from cost share drugs to reference drugs. Reference pricing may reduce related expenditures with effects on reference drugs but the effect on expenditures of cost share drugs is uncertain. Reference pricing may increase the use of reference drugs and may reduce the use of cost share drugs. The analysis and reporting of the effects on patients' drug expenditures were limited in the included studies and administration costs were not reported. Reference pricing effects on health are uncertain due to lack of evidence. The effects of other purchasing and pricing policies are until now uncertain due to sparse evidence. However, index pricing may reduce the use of brand drugs, increase the use of generic drugs, and may also slightly reduce the price of the generic drug when compared with no intervention.

Twenty years of elemental analysis of marine biota within the German Environmental Specimen Bank--a thorough look at the data.

PURPOSE: As one component of the German ecological environment observation, the Environmental Specimen Bank program was initiated in the mid-1980s. Under the program, representative specimens of marine, fresh water, and terrestrial ecosystems are sampled regularly and archived under chemically stable conditions. An initial characterization of the samples provides data regarding the status quo of the respective ecosystems. The aim of the present publication is to give insight into these real-time monitoring data, which have been generated for the last 10 to 20 years. This is done exemplarily for the heavy metals cadmium (Cd), mercury (Hg), and lead (Pb) in marine specimens of the Baltic and the North Sea. METHODS: Bladder wrack (Fucus vesiculosus), blue mussel (Mytilus edulis), eelpout (Zoarces viviparus), and eggs of herring gulls (Larus argentatus) were sampled at one location in the Baltic Sea and at two sites in the North Sea (Schleswig-Holstein Wadden Sea and Lower Saxony Wadden Sea). Annual samples were pooled, homogenized, and analyzed for a set of elements. Cd and Pb were quantified after freeze-drying and microwave digestion using inductively coupled plasma-mass spectrometry. Total Hg in freeze-dried samples was determined by atomic absorption spectrometry using a direct mercury analyzer. RESULTS: Time series data covering up to two decades revealed comparable cadmium levels at all three locations. Concentrations in bladder wrack ranged between 0.10 and 0.37 microg/g on a wet weight basis (ww). Respective values for blue mussel and eelpout liver were 0.07-0.29 and 0.01-0.10 microg/g ww. Herring gull eggs were not included in cadmium analyses. Declining trends were observed in North Sea bladder wrack and mussels, eelpout from the Lower Saxony site, and mussels from the Baltic Sea. Upward trends were apparent in eelpout from the Schleswig-Holstein location. Mercury concentrations in Baltic Sea specimens ranged from 1.1-2.7 ng/g ww in bladder wrack to 2.6-5.1, 26-52, and 86-226 ng/g ww in blue mussel, eelpout muscle, and herring gull eggs, respectively. No temporal trends were observed. North Sea bladder wrack had accumulated 5.4-24 ng/g ww Hg. The respective Hg values for blue mussel and eelpout muscle were 19-64 and 73-187 ng/g ww. Highest Hg contents were detected in herring gull eggs (90-1,100 ng/g ww). Declining trends of Hg were observed in herring gull eggs at both North Sea locations and in blue mussels at the Lower Saxony site. Lead concentrations in Baltic Sea specimens were 48-222 ng/g ww in bladder wrack, 85-189 ng/g ww in blue mussel, 2.0-9.5 and 10-42 ng/g ww in eelpout muscle and liver, and 2.7-26 ng/g ww in herring gull eggs. In the North Sea, Pb concentrations were as follows: 68-397 ng/g ww in bladder wrack, 101-507 ng/g ww in blue mussels, 2.6-35 and 5.9-158 ng/g ww in eelpout muscle and liver, and 3.5-55 ng/g ww in herring gull eggs. Highest Pb-levels were found at the Lower Saxony site. Declining Pb-trends were observed in bladder wrack from the Baltic Sea; in bladder wrack and mussel at the Schleswig-Holstein location; and in bladder wrack, mussels, eelpout liver, and herring gull eggs at the Lower Saxony site. CONCLUSIONS: During the 10 to 20 years of monitoring, reliable data were obtained which allow a good insight into metal contamination of marine biota. Assessment of the data according to OSPAR criteria (OSPAR 2005) revealed cadmium levels above the derived background concentrations in mussels of all three sites. Mercury levels above background concentrations were found at both North Sea locations, whereas only mussels at the Lower Saxony site had Pb concentrations above the reference value. Archived specimens are available for further analyses and questions which may arise in the future (speciation of elements, metallomics).

Methylated arsenic, antimony and tin species in soils.

Methylated species of antimony, arsenic and tin were examined in urban soils of the Ruhr basin, near the cities of Duisburg and Essen, Germany. The main aim of this study was to investigate the occurrence of mono-, di- and trimethylated species of these elements in urban soils. The influence of historical and present land use upon the species content was examined. The distribution of inorganic As, Sb and Sn and their methylated species along the profile depth was investigated. As, Sb and Sn speciation was performed by pH-gradient hydride generation purge and trap gas chromatography, followed by inductively-coupled plasma mass spectrometry (HG-PT-GC/ICP-MS). Species' structures were confirmed by GC-EI/MS-ICP-MS. Monomethylated Sb and As were the dominant species detected: the concentration of these metal(loid) species varied between <0.07-56 microg kg(-1) per dry mass. All dimethylated species and monomethyltin concentrations were between <0.01-7.6 microg kg(-1) per dry mass, and for the trimethylated species of all examined elements, concentrations between <0.001-0.63 microg kg(-1) per dry mass were detected. The highest organometal(loid) concentrations were observed in agricultural soils and garden soils; lower concentrations were found in the soils of abandoned industrial sites (wasteland, primary forest and grassland) and a flood plain soil of the Rhine. This result can be ascribed to both the cultivation and the increased biological activity of the agricultural soils, and the generally higher contamination, the disturbed structure and the artificial substrates (deposits from industrial sources) of the abandoned industrial soils. Due to periodical sedimentation, the flood plain profile was the only one where no depth dependence of organometal(loid) species concentration was detected. The other soil profiles showed a decrease of species content with increasing depth; this was particularly noticeable in soils with a clear change from a horizon with an organic character towards a mineral horizon, i.e. decreasing vitality from profile top to bottom. It is not as yet clear whether the organometal(loid) species are formed in the mineral horizons of the profiles or whether they are displaced from the organic, biologically-active horizons towards the mineral horizons. Field studies revealed that soil parameters like pH, water content or temperature did not correlate significantly with the degree of biomethylation observed. In contrast to the lower in vitro biomethylation efficiency of Sb vs. As in microbial incubations, we consistently detected higher proportions of transformed Sb compounds in situ in soil samples. These data may indicate a need to re-examine the currently accepted model of Sb biogeochemical cycling in the real environment.