Conditional approval of cancer drugs in Canada: accountability and impact on public funding.

Background: We examined how conditional market approval of cancer pharmaceuticals by Health Canada (hc) affects public funding recommendations by the pan-Canadian Oncology Review (pcodr). We were also interested to see how often hc conditions are enforced. Methods: Health Canada and pcodr databases for 2010-2017 were analyzed for patterns in hc conditional authorization and post-authorization reviews of cancer drugs and for correlation with pcodr reimbursement recommendations. Results: Between 2010 and 2017, pcodr reviewed 105 unique drug-indication pairings; 21% (n = 22) had conditional hc authorization. In all cases, conditional authorization was given on the basis of preliminary data in a surrogate endpoint and was contingent on further data showing benefit in more robust outcome measures (for example, overall survival). Of those 22 drugs, 36% did not have updated data, 36% had updated data that met hc conditions, and 27% had data that met some, but not all, conditions. During the period considered, hc never revoked conditional authorization for failure to meet conditions. None of the 22 drugs was given an unconditional positive recommendation for public reimbursement by pcodr. A conditional recommendation was given to 11 of the drugs (50%), and reimbursement was not recommended for 6 drugs (27%) because of insufficient evidence. Conclusions: One fifth of the cancer drugs reviewed for public reimbursement in Canada were conditionally authorized by hc based on preliminary data. Conditional authorization was associated with a recommendation against public funding by pcodr. No drugs had their conditional market authorization revoked for failure to meet conditions, suggesting that a more robust hc reappraisal framework is needed.

Understanding the reasons for provincial discordance in cancer drug funding-a survey of policymakers.

Background: Cancer drug-funding decisions between provinces shows discordance. The pan-Canadian Oncology Drug Review (pcodr) was implemented in 2011 partly to address uneven drug coverage and lack of transparency in the various provincial cancer drug review processes in Canada. We evaluated the underlying reasons for ongoing provincial discordance since the implementation of pcodr. Methods: Participation in an online survey was solicited from participating provincial ministries of health (mohs) and cancer agencies (cas). The 4-question survey (with both multiple-choice and free-text responses) was administered between 4 March 2015 and 1 April 2015, inclusive. Anonymity was ensured. Descriptive statistics were used to evaluate responses. Results: Data were available from 9 provinces (all Canadian provinces except Quebec), with a response rate of 100%. The 12 responses received each came from a senior policymaker with more than 5 years' experience in cancer drug funding decision-making (5 from mohs, 7 from cas). Responses for 3 provinces came from both a moh representative and a ca representative. The most common reason for funding a drug not recommended by pcodr was political pressure (64%). The most common reason not to fund a drug recommended by pcodr was budget constraints (91%). The most common reason for a province to fund a drug before completion of the pcodr review was also political pressure (57%). Conclusions: Political pressure and budgetary constraints continue to affect equity of access to cancer drugs for patients throughout Canada.

Impact of the pan-Canadian Oncology Drug Review on provincial concordance with respect to cancer drug funding decisions and time to funding.

BACKGROUND: The pan-Canadian Oncology Drug Review (pcodr) was implemented in 2011 to address uneven drug coverage and lack of transparency with respect to the various provincial cancer drug review processes in Canada. We evaluated the impact of the pcodr on provincial decision concordance and time from Notice of Compliance (noc) to drug funding. METHODS: In a retrospective review, Health Canada's Drug Product Database was used to identify new indications for cancer drugs between January 2003 and May 2014, and provincial formulary listings for drug-funding dates and decisions between 1 January 2003 and 31 December 2014 were retrieved. Multiple linear models and quantile regressions were used to evaluate changes in time to decision-making before and after the implementation of the pcodr. Agreement of decisions between provinces was evaluated using kappa statistics. RESULTS: Data were available from 9 provinces (all Canadian provinces except Quebec), identifying 88 indications that represented 51 unique cancer drugs. Two provinces lacked available data for all 88 indications at the time of data collection. Interprovincial concordance in drug funding decisions significantly increased after the pcodr's implementation (Brennan-Prediger coefficient: 0.54 pre-pcodr vs. 0.78 post-pcodr; p = 0.002). Nationwide, the median number of days from Health Canada's noc date to the date of funding significantly declined (to 393 days from 522 days, p < 0.001). Exploratory analyses excluding provinces with incomplete data did not change the results. CONCLUSIONS: After the implementation of the pcodr, greater concordance in cancer drug funding decisions between provinces and decreased time to funding decisions were observed.

Nanoliter capillary electrochromatography columns based on collocated monolithic support structures molded in poly(dimethyl siloxane).

Following current trends in miniaturization of analytical chemistry, an inexpensive disposable analytical tool in the form of a liquid chromatography column fabricated on a poly(dimethyl siloxane) (PDMS) chip was created. Ease of fabricating the chromatography column was demonstrated by molding collocated monolithic support structures (COMOSS) directly in the column. Positive photo-resist, SPR 220, was used to create column structures on a negative relief master providing final channel dimensions of 2.7-5.2 microm wide by 10.0 microm deep, while monolithic dimensions were 9.8 x 9.8 x 10.0 microm - 12.3 x 12.3 x 10.0 microm. The ability to separate biological samples such as peptides from a tryptic digest of fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) was shown. Separations in capillary electrochromatographic (CEC) mode were performed yielding column efficiencies of 4.0 x 10(5) plates/m.

Simultaneous determination of dihydroxybenzenes, aminophenols and phenylenediamines in hair dyes by high-performance liquid chromatography on hypercross-linked polystyrene.

The retention of polar organic molecules such as dihydroxybenzenes, aminophenols and phenylenediamines on a 250 x 4.6 mm id column packed with 5 microns hypercross-linked polystyrene Chromalite 5HGN (Purolite) was studied. The influence of separation parameters such as concentration of acetonitrile, buffer (citrate, phosphate) concentration, ionic strength and pH of the eluent on their retention was investigated. Under optimum conditions [acetonitrile-0.3 mol l-1 ammonium phosphate, pH 5.15 (30:70 v/v)], eight substances generally used as dye intermediates in hair colouring compositions could be separated within 20 min. An HPLC method with spectrophotometric detection is proposed for the simultaneous determination of pyrocatechol, resorcinol, hydroquinone, o-, m- and p-aminophenols and p-phenylenediamine in commercial haircolour products. The detection limits of these compounds are in the range 0.05-0.16 microgram ml-1. The suitability of the method is demonstrated by the analysis of three different permanent hair dyes.

Application of neutral hydrophobic hypercrosslinked polystyrene to the separation of inorganic anions by ion chromatography.

Neutral hydrophobic hypercrosslinked polystyrene was shown to exhibit anion-exchange properties in the pH range 2.6-4.3 that can be attributed to the presence of protonated carbonyls in the framework of the polymer. This resin does not contain any other heteroatoms, except oxygen, responsible for the occurrence of positive charge at the surface. The anion-exchange selectivity of MN-200 and monosized spherical hypercrosslinked polystyrene to inorganic anions with diluted perchloric, nitric and sulfuric acid solutions as eluent was studied and the selectivity was found to be different from that observed for the common anion-exchangers. The main features of hypercrosslinked polystyrene are weak retention of sulphate and comparatively strong retention of nitrite that can be useful in practical ion chromatography. The influence of column temperature on the retention was investigated. Calculated adsorption heats are in the range from -2 to 19 kJ/mol. The retention mechanism of inorganic anions on neutral hypercrosslinked polystyrene includes both ion-exchange and hydrophobic interactions.

Background on the Oregon Health Plan.

Because of limited resources, the health care industry has been forced to choose how funds are spent. Public fee-for-service systems have begun to face the hard choices inherent in managed care. The Oregon Health Plan was designed to provide a rational approach to addressing these changes directly.

Integrating mental health into the Oregon Health Plan.

Public mental health has long struggled to be accepted as a part of health care. Its interface with social services and its broad spectrum of professionals make a clear definition of public mental health's boundaries difficult, fueling policymakers' skepticism about such acceptance. The Oregon Health Plan was the result of a process that explicitly included mental health but recognized that the tools for doing so need to be carefully developed.