Response to "Canadians Need Improved Access to Drugs for Rare Diseases, Not More Denial".

The comments provided by Rawson and Adams (2023) miss the mark of our articles (Sirrs et al. 2023a, 2023b). We agree that the patient perspective is critical and that patients with "rare diseases have a right to healthcare and have huge unmet needs …" (p. 7). However, we challenge Rawson and Adams' (2023) thesis that keeping drug prices higher in Canada than in most other countries would solve the problem of access to therapies for rare diseases that have no available treatment.

Expensive Drugs for Rare Diseases in Canada: What Value and at What Cost?

There has been explosive growth in the market for expensive drugs for rare diseases (EDRDs). Traditional standards of evidence are not achievable for rare diseases, so lower standards are applied. The price of these drugs is extremely high. This combination of lower standards and higher prices make EDRDs attractive to manufacturers. Legislation designed to incentivize drug development for rare diseases contains loopholes that drive prices up worldwide. Canada compounds those problems with a complex network of agencies that impede communication between those providing market authorization and those purchasing drugs. Drug pricing is not related to metrics like investment or value, but rather willingness to pay. Without high-quality evidence to assess value, we inadvertently prioritize patients with rare diseases over those with common diseases, creating conflict among ethical principles such as social utility, justice and the rule of rescue. Lack of transparency over what is being funded and for whom makes it hard to mitigate challenges through effective policy development. We review the evidentiary, economic and ethical issues around EDRDs and ways to move forward, including enhanced transparency and the development of high-quality evidence to ensure that we do not pay for drugs that do not work.

Expensive Drugs for Rare Diseases in Canada: Time for Action Everywhere and by Everyone.

Expensive drugs for rare diseases pose unique economic, evidentiary and ethical challenges, and these will continue to escalate unless steps are taken urgently to address these challenges. We propose concrete actions that all stakeholders (federal and provincial/territorial governments, patients, healthcare providers, the public and drug manufacturers) could take now as a first step toward enhancing sustainability in the use of innovative (albeit expensive) therapies within our publicly funded healthcare system.

Meta-analysis of neuropsychological measures of executive functioning in children and adolescents with high-functioning autism spectrum disorder.

Existing literature on the profile of executive dysfunction in autism spectrum disorder showed inconsistent results. Age, comorbid attention-deficit/hyperactivity disorder (ADHD) and cognitive abilities appeared to play a role in confounding the picture. Previous meta-analyses have focused on a few components of executive functions. This meta-analysis attempted to delineate the profile of deficit in several components of executive functioning in children and adolescents with high-functioning autism spectrum disorder (HFASD). Ninety-eight English published case-control studies comparing children and adolescents with HFASD with typically developing controls using well-known neuropsychological measures to assess executive functions were included. Results showed that children and adolescents with HFASD were moderately impaired in verbal working memory (g = 0.67), spatial working memory (g = 0.58), flexibility (g = 0.59), planning (g = 0.62), and generativity (g = 0.60) except for inhibition (g = 0.41). Subgroup analysis showed that impairments were still significant for flexibility (g = 0.57-0.61), generativity (g = 0.52-0.68), and working memory (g = 0.49-0.56) in a sample of autism spectrum disorder (ASD) subjects without comorbid ADHD or when the cognitive abilities of the ASD group and the control group were comparable. This meta-analysis confirmed the presence of executive dysfunction in children and adolescents with HFASD. These deficits are not solely accounted for by the effect of comorbid ADHD and the general cognitive abilities. Our results support the executive dysfunction hypothesis and contribute to the clinical understanding and possible development of interventions to alleviate these deficits in children and adolescents with HFASD. Autism Res 2017, 10: 911-939. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Drug use evaluation of moxifloxacin (avelox) using a hand-held electronic device at a canadian teaching hospital.

BACKGROUND: The use of moxifloxacin (Avelox) has increased at Vancouver General Hospital since its introduction onto the formulary in 2002. It is unclear, however, whether the use of the drug is optimal according to its indication. Hand-held electronic devices, such as personal digital assistants (PDAs), are novel tools that can be used during routine patient care to collect data for drug use evaluation (DUE) reviews. OBJECTIVE: We hypothesized that moxifloxacin was over-utilized and that opportunities existed to optimize its use. This study was designed to characterize moxifloxacin use in concordance with evidence-based assessment criteria. The feasibility of using a PDA device as a data-collection tool was also evaluated. DESIGN: An observational DUE was conducted over a 4-week period (from February 17 to March 16, 2007) at Vancouver General Hospital, a 955-bed tertiary care hospital. Inpatients who received at least one dose of moxifloxacin were enrolled. Evidence-based assessment criteria were developed to evaluate the appropriateness of moxifloxacin use, and a PDA database was developed for data collection. The primary endpoint was the proportion of moxifloxacin use for approved first-line indications. RESULTS: A total of 132 patients were included. Eighty-nine patients (67%) received moxifloxacin for first-line indications, including community-acquired pneumonia (57%) and acute exacerbation of chronic bronchitis (10%). Forty-three patients (33%) had alternative indications, primarily hospital-acquired pneumonia (25%). In 129 evaluable patients, approximately half (51%) of the clinical outcomes were successful; 37% were indeterminate; and 12% were failures. General medicine and respiratory service clinicians prescribed moxifloxacin more appropriately compared with surgical service personnel. Most of the pharmacists supported the use of PDAs as DUE data-collection tools. CONCLUSION: Overall, moxifloxacin utilization at Vancouver General Hospital was appropriate according to evidence-based assessment criteria. Additional opportunities to improve its use exist through health care staff education. PDAs are ideal data-collection tools for DUEs, as they can be conveniently used during routine patient care.