Szymon Jarosławski | Aix-Marseille University (original) (raw)

Papers by Szymon Jarosławski

Background: We sought to assess if orphan oncology drugs that target smaller populations are cost... more Background: We sought to assess if orphan oncology drugs that target smaller populations are costlier than those that target larger ones. Methods: A list of orphan drugs designated by the FDA and diseases prevalence was retrieved from the FDA. Average Wholesale Prices per unit were obtained from the Red book database. Finding: Between June 2011 and June 2016, the FDA approved 31 unique regimens. Their annual treatment costs ranged from 9474to9474 to 9474to230,400, with a median of $140,893. Interpretation: There was no linear or exponential relationship between drug price and the size of their patient population. Further research is needed to bring more transparency of drug pricing in the US and align the prices of orphan drugs with the target population size and other relevant factors.

In wealthy nations, non-profit drug R&D has been proposed to reduce the prices of medicines. We s... more In wealthy nations, non-profit drug R&D has been proposed to reduce the prices of medicines. We sought to review the ethical and economic issues concerning non-profit drug R&D companies, and the possible impact that their pricing strategy may have on the innovation efforts from for-profit companies targeting the same segment of the pharmaceutical market. There are two possible approaches to pricing drugs developed by non-profit R&D programs: pricing that maximises profits and Baffordable^pricing that reflects the cost of manufacturing and distribution, plus a margin that ensures sustainability of the drug supply. Overall, the non-profits face ethical challenges -due to the lack of resources, they are unable to independently commercialize their products on a large scale; however, the antitrust law does not permit them to impose prices on potential licensees. Also, reduced prices for the innovative products may result in drying the for-profit R&D in the area.

Background: Orphan drugs (ODs) are pharmaceuticals manufactured for rare conditions that affect l... more Background: Orphan drugs (ODs) are pharmaceuticals manufactured for rare conditions that affect less than 200,000 people in the US. ODs are therefore produced in small quantities to meet sparse demand. Since 2010, OD shortages have become frequent, but no comprehensive, quantitative studies exist. Objective: The objective of this study is to assess the rates of OD shortages per therapeutic class and their trends over time in the United States. Study design: OD approvals were collected from publicly available information on the US Food and Drug Administration (FDA) website on 13 June 2016. Data on OD shortages were collected from the FDA and the American Society of Health-System Pharmacists (ASHP) websites. We reviewed the number of shortages per year and per therapeutic area. Multiple indications for the same drug were counted individually. Results: Of 569 ODs approved, 50% were approved in the decade ending in 2015. Oncology was found to be the most represented therapeutic area (34% of all OD approvals), followed by endocrinology (11%). Shortage data were available from 2008. In total, there were 66 (12%) OD shortages, with an average shortage duration of 455.5 days. Shortages were observed mainly for oncology products (19 cases, 13% of oncology ODs) and endocrinology products (14 cases, 22% of endocrinology ODs) Conclusion: Despite the FDA strategic plan for preventing and mitigating drug shortages (October 2013), remaining OD shortages still pose an enduring challenge to patient care, with a median shortage duration of almost 15 months. In many instances, ODs are the only available therapy for rare diseases, and OD shortages can lead to serious health deterioration and death. More research is needed to elucidate the causes of shortages and their impact on patients' health.

Background: Claims included in package inserts (PIs) for medicinal products approved by the US Fo... more Background: Claims included in package inserts (PIs) for medicinal products approved by the US Food and Drug Administration (FDA) constitute the regulatory definition of drugs' benefits and risks. Objective: We sought to assess the usage of patient-reported outcome (PRO) claims in a comprehensive set of US FDA orphan drug approvals dated between 1/1/2012 and 31/12/2016, and characterize them. Study design: Orphan drug approval documentation was obtained from the US FDA website. Drug Package Inserts (PI) were analyzed to extract information on PRO-related language. Results: Among 178 drugs that met inclusion criteria, 16 (9%) products approved for 16 orphan indications contained PRO language in the Clinical Studies section of the PI. All PRO instruments concerned disease symptoms, and two also referred to patient functioning. The most common PRO instrument was a bleed-specific rating scale for four products approved for the treatment or prevention of bleeding episodes in patients with genetic bleeding disorders. Conclusions: There is a need to implement public incentives for academic development of PRO instruments for rare conditions and for regulatory policies that mandate the collection of PRO endpoints in pivotal trials of orphan drugs.

Purpose: We aimed to evaluate the rate of usage and the kind of patient-reported outcome (PRO) cl... more Purpose: We aimed to evaluate the rate of usage and the kind of patient-reported outcome (PRO) claims in orphan drug approvals from the European Medicines Agency (EMA) dated between 1/1/2012 and 31/12/2016 and to compare them to those from the US Food and Drug Administration (FDA). Methods: Orphan drug approval documentation was obtained from the EMA website. PROrelated language was extracted from the Summaries of Product Characteristics (SmPCs). Data were compared to a previously published analysis of the FDA approvals from the same time period. Results: Out of 60 approvals that met the inclusion criteria, 12 products approved by the EMA for 13 (21.7%) orphan indications contained PRO language in the Clinical Studies section of the SmPC. Twelve SmPCs contained PRO instruments based on symptoms, five of which also concerned patient functioning. Eight approvals included PRO claims related to quality of life (QoL) most commonly in cancer treatment. Conclusion: The rate of PRO claims was lower for orphan drugs specifically than for all drug approvals by the EMA. However, in accordance with previous findings, the EMA appeared more inclined to grant PRO claims including health-related QoL than the FDA.

Non-profit drug research and development (R&D) has the potential to deliver innovative treatments... more Non-profit drug research and development (R&D) has the potential to deliver innovative treatments at affordable prices. Using the case study methodology, we discuss some ethical and economic issues, including the possible impact of non-profit companies on innovation efforts from for-profit firms. Like other non-profits, Genethon is willing to adopt an ethical attitude toward their donors by pricing their products affordably. It remains to be seen if the approach to internalize the marketing authorization, manufacturing and distribution activities prove to be efficient and sustainable. Also, the firm faces an ethical dilemma because lower prices of innovative drugs can dry the for-profit R&D in the area and prevent patient access to future innovations.

Biophysical Analysis of Membrane Proteins, 2007

Page 1. Atomic Force Microscopy: High - Resolution Imaging of Structure and Assembly of Membrane ... more Page 1. Atomic Force Microscopy: High - Resolution Imaging of Structure and Assembly of Membrane Proteins Simon Scheuring , Nikolay Buzhynskyy , Rui Pedro Gon ç alves and Szymon Jaroslawski 6.1 Atomic Force Microscopy 6.1.1 Sample Preparation ...

Value in Health, 2010

A247 resulting in cost-effectiveness different to that of younger cohorts that receive the comple... more A247 resulting in cost-effectiveness different to that of younger cohorts that receive the complete intervention: multi-cohort models can include both these "complete" and "partial" cohorts. Some multi-cohort models described as population models impose fi nite time horizons at which the intervention is assumed to cease, although health effects are typically assessed until death. ANALYSIS: If cost-effectiveness differs between partial and complete cohorts, then the overall cost-effectiveness estimate from a multi-cohort model will depend on the relative numbers of partial and complete cohorts. The total number of complete cohorts depends on how long the intervention is used, which is uncertain. Therefore, the overall estimate may depend, in part, on the number of future cohorts assumed. The appropriateness of time horizons depends on whether a cross-sectional or a longitudinal cohort approach is used. Assuming an intervention ceases at a time horizon is unrepresentative of actual implementation and may result in biased cost-effectiveness estimates for curtailed cohorts. CONCLUSION: Multi-cohort modeling is advocated as being more representative of actual implementation. However, a single cost-effectiveness estimate for multiple cohorts necessarily implies an aggregation of estimates. Such aggregation leaves estimates sensitive to assumptions of the number of cohorts included, can hide useful information, and lead to nonoptimal policy choices. We suggest cost-effectiveness estimates for the complete and incomplete cohorts should not be aggregated, but reported separately. Implementation time horizons should not be used in longitudinal cohort-based modeling in cost-effectiveness analysis. BACKGROUND: Cost-effectiveness models are often used to predict the costs and health outcomes that are likely to be associated with various different interventions. Models are a useful tool for representing the detailed and complex "real world" in a more simple and understandable structure. While models do not claim to necessarily create an exact replica of the real world, they can be useful in demonstrating the relationships and interactions between various different factors. However, developers of models often consciously, and unconsciously, make assumptions that are avoidable and may bias the results of a model. METHODS: A review was undertaken on a random selection of published models in different disease areas to aim to identify the frequency of typical "errors" in economic models. In addition, a simple model was developed and used to explore the relative impact of different types of errors in models. Each type of error was examined for its likely impact on the model's overall fi ndings and conclusions. This helped to gain a greater understanding of both the frequency of different errors and their magnitude of effect. RESULTS: Mistakes are commonly observed in economic models. These were often due to limitations in scope of the model, but all were found to be avoidable given unlimited time and data availability. As well as identifying "major" errors in models, the review also identifi ed many common errors, such as excluding "half cycle correction," that often have very little impact on a model's results, relative to other common errors. CONCLUSIONS: While many errors in economic models are frequent, many errors often go unnoticed and have signifi cant impact upon a model's results. This analysis has highlighted the relative importance of each type of error and has provided suggestions as to how these might be avoided.

Value in Health, 2010

OBJECTIVES: To examine drug cost containment policy implemented at a hospital in southern Thailan... more OBJECTIVES: To examine drug cost containment policy implemented at a hospital in southern Thailand. METHODS: This study was a retrospective, pre-post policy intervention descriptive design. During the fi scal years of 2005 and 2009, various drug cost containment strategies, including generic substitution for any drug group and a successful treatment guideline for orthopedic drugs, were adopted at a hospital in southern Thailand. Drug expenditures across those fi scal years were examined. The expenditure proportions between drugs listed and unlisted in National Essential Drug List were calculated. Cost-saving analysis of all generic substitution was conducted. Since the treatment guideline for orthopedic drugs was available in the hospital, their expenditures were also examined. RESULTS: Total drug expenditures had increased with decreasing rate across the study years. It increased by 47.15% from year 2005 to 2006, 43.19% from year 2006 to 2007, 21.17% from year 2007 to 2008 and 2.17% from year 2008 to 2009. The expenditures of essential drugs in the National Drug List were accounted for 61.64%, 56.62%, 54.38%, 48.67% and 50.94% across those study periods, respectively. Results showed that generic drug substitution policy reduced overall drug expenditures by 34.33%, or 7.66 million baths from year 2008. In 2009, only 11 items of generic drug substitution for branded-name drugs could reduce drug expenditures by 13.33%, or 4.73 million bahts which refl ected annual cost-saving about 25.95 million bahts. In the same year, a result showed that the implementation of orthopedic drug guideline reduced drug expenditures by 5.53% or 2.10 million bahts. CONCLUSIONS:

The high cost of novel treatments is the major driver of negative or restricted reimbursement dec... more The high cost of novel treatments is the major driver of negative or restricted reimbursement decisions by healthcare payers in many countries. Costly drugs can be subject to Market Access Agreements (MAAs), which are financial (Commercial Agreements [CAs]) or outcomes-based (Payment for Performance Agreements [P4Ps] or Coverage with Evidence Development agreements [CEDs]). Outcomes in outcomes-based MAAs are assessed through changes in surrogate endpoints (SEPs) or patient-relevant endpoints (PEPs). In May 2015, we reviewed published and grey literature on MAAs between manufacturers and large, institutionalised payers from all geographical areas, and classified the schemes into CAs, P4Ps and CEDs, as well as by therapeutic area and country. Outcomes-based MAAs were further categorized by the endpoint used. Overall, we identified 143 MAAs, 56 (39.2 %) of which were pure CAs, 53 (37.1 %) were CEDs, and 34 (23.8 %) were P4Ps. Among the CEDs, 49 were PEP CEDs and four were SEP CEDs; of the 34 P4Ps, 29 were SEP P4Ps for 30 drugs, and five were PEP P4Ps for at least six drugs; and among 87 outcomes-based MAAs (CEDs ? P4Ps), PEP CEDs were the most common (56.3 %), followed by SEP P4Ps (34.1 %). The high proportion of SEPs used in P4Ps contrasts with the high proportion of PEPs used in CEDs. CEDs employ PEPs and it appears that they are used to reduce uncertainty about a drug's clinical outcomes and/or real-life use, and thus allow payers to align a product's value with price. We argue that P4Ps do not reduce uncertainty about real-life effectiveness and can only constitute an outcome guarantee for payers if they are based on PEPs or validated SEPs.

Approved by the US Food and Drug Administration (FDA) in 2010, sipuleucel-T (Provenge(®)) was the... more Approved by the US Food and Drug Administration (FDA) in 2010, sipuleucel-T (Provenge(®)) was the first 'personalized' cancer vaccine for the treatment of prostate cancer in a metastatic, non-symptomatic population of 30,000 men in the USA. Sipuleucel-T is prepared individually for each patient and infused in three sessions over a period of 1 month. However, in 2015, Dendreon, the owner of sipuleucel-T, filed for bankruptcy. This opinion paper reviews the probable reasons this innovative product failed to achieve commercial success. PubMed and internet searches were performed focused on pricing, reimbursement, and market access. We found that sipuleucel-T's FDA approval was delayed by 3 years, reportedly because of the vaccine's new mechanism of action. Sipuleucel-T was cleared by the European Medicines Agency 2 years later, but other national agencies were not approached. It was priced at US93,000foracourseoftreatment,andthishighpricecombinedwiththecompany′slatesecurementofreimbursementforthevaccinebytheUSCentersforMedicareandMedicaidServices(CMS)resultedinanotheryear′sdelayinaccessingthemarket.DespiteapositiverecommendationbytheNationalComprehensiveCancerNetwork,sipuleucel−T′scomplexadministration,highprice,anduncertaintyaboutthereimbursementstatusdeterreddoctorsfromprescribingtheproduct.Furthermore,thevaccine′ssupplywaslimitedduringthefirstyearoflaunchduetolimitedmanufacturingcapacity.Inaddition,twooralmetastaticprostatecancerdrugswithsimilarsurvivalbenefitsreachedtheUSmarket1and2yearsaftersipuleucel−T.Also,eventhoughDendreon′smarketcapitalizationtoppedUS93,000 for a course of treatment, and this high price combined with the company's late securement of reimbursement for the vaccine by the US Centers for Medicare and Medicaid Services (CMS) resulted in another year's delay in accessing the market. Despite a positive recommendation by the National Comprehensive Cancer Network, sipuleucel-T's complex administration, high price, and uncertainty about the reimbursement status deterred doctors from prescribing the product. Furthermore, the vaccine's supply was limited during the first year of launch due to limited manufacturing capacity. In addition, two oral metastatic prostate cancer drugs with similar survival benefits reached the US market 1 and 2 years after sipuleucel-T. Also, even though Dendreon's market capitalization topped US93,000foracourseoftreatment,andthishighpricecombinedwiththecompany′slatesecurementofreimbursementforthevaccinebytheUSCentersforMedicareandMedicaidServices(CMS)resultedinanotheryear′sdelayinaccessingthemarket.DespiteapositiverecommendationbytheNationalComprehensiveCancerNetwork,sipuleucel−T′scomplexadministration,highprice,anduncertaintyaboutthereimbursementstatusdeterreddoctorsfromprescribingtheproduct.Furthermore,thevaccine′ssupplywaslimitedduringthefirstyearoflaunchduetolimitedmanufacturingcapacity.Inaddition,twooralmetastaticprostatecancerdrugswithsimilarsurvivalbenefitsreachedtheUSmarket1and2yearsaftersipuleucel−T.Also,eventhoughDendreon′smarketcapitalizationtoppedUS7.5 billion following the FDA's approval of sipuleucel-T, this value degraded gradually until the firm's bankruptcy 5 years later. We conclude that the bankruptcy of Dendreon was largely due to the delay in securing FDA approval and CMS coverage, as well as the high cost that had to be incurred by providers up-front. Licensing sipuleucel-T to a pharmaceutical company more experienced in the market access pathway may have saved the company and the product.

Background: India is a country with vast unmet medical needs. eHealth has the potential to improv... more Background: India is a country with vast unmet medical needs. eHealth has the potential to improve the quality of health care and reach the unreached. We have sought to understand the kinds of eHealth programmes being offered in India today, the challenges they face and the nature of their financing. Methods: We have adopted an interview-based methodology. The 30 interviews represent 28 organizations, and include designers, implementers, evaluators and technology providers for eHealth programmes. Results: A range of programmes is being run, including point-of-care in rural and urban areas, treatment compliance, data collection and disease surveillance, and distant medical education. Most programmes provide point-ofcare to patients or other beneficiaries in rural areas. Technology is not a limiting factor but the unavailability of suitable health personnel is a major challenge, especially in rural areas. We have identified a few factors that help this situation. Financial sustainability is also a concern for most programmes, which have rarely been scaled up. There are recent for-profit efforts in urban areas, but no reliable business model has been identified yet. Government facilities have not been very effective in eHealth on their own, but collaborations between the government and non-profit (in particular) and for-profit organisations have led to impactful programmes.

Journal of epidemiology and global health, 2012

Serological tests for tuberculosis are inaccurate and WHO has recommended against their use. Alth... more Serological tests for tuberculosis are inaccurate and WHO has recommended against their use. Although not used by the Revised National TB Control Programme (RNTCP), serodiagnostics are widely used in the private sector in India. A root-cause analysis was undertaken to determine why serological tests are so popular, and seven root causes were identified that can be grouped into three categories: technical/medical, economic, and regulatory. Technical/medical: RNTCPÕs current low budget does not allow scale-up of the newer, WHO-endorsed technologies. Thus, under the RNTCP, most patients have access to only smear microscopy, a test that is insensitive and underused in the private sector. Because there is no accurate, validated, point-of-care test for TB, serological tests meet a perceived need among doctors and patients. Economic: While imported molecular or liquid culture tests are too expensive, there are no affordable Indian versions on the market, leaving serological tests as the main alternative. Although serological tests are inaccurate, various players along the value chain profit from their use, and this sustains a market for these tests. Regulatory: TB tests are poorly regulated and a large number of serological kits are on the market. Private healthcare in general is poorly regulated, and doctors in the private sector are outside the scope of RNTCP and do not necessarily follow standard guidelines. A clear understanding of these realities should facilitate market-based strategies that can help replace serological tests with accurate, validated tools.

BMC health services research, 2013

Background: Over 75% of the medical devices used in India are imported. Often, they are costly an... more Background: Over 75% of the medical devices used in India are imported. Often, they are costly and maladapted to low-resource settings. We have prepared case studies of six firms in Bangalore that could contribute to solving this problem. They have developed (or are developing) innovative health care products and therefore are pioneers in the Indian health care sector, better known for its reverse engineering skills. We have sought to understand what enablers and barriers they encountered. Methods: Information for the case studies was collected through semi-structured interviews. Initially, over 40 stakeholders of the diagnostics sector in India were interviewed to understand the sector. However the focus here is on the six featured companies. Further information was obtained from company material and other published resources.

Biophysical Analysis of Membrane Proteins, 2007

Value in Health, 2010

Journal of epidemiology and global health, 2012

BMC health services research, 2013