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Ashraf AR, Mackey TK, Vida RG, Kulcsár G, Schmidt J, Balázs O, Domián BM, Li J, Csákó I, Fittler A. Multifactor Quality and Safety Analysis of Semaglutide Products Sold by Online Sellers Without a Prescription: Market Surveillance, Content Analysis, and Product Purchase Evaluation Study. J Med Internet Res 2024; 26:e65440. [PMID: 39509151 PMCID: PMC11582493 DOI: 10.2196/65440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 09/18/2024] [Accepted: 09/19/2024] [Indexed: 11/15/2024] Open
Abstract
BACKGROUND Over the past 4 decades, obesity has escalated into a global epidemic, with its worldwide prevalence nearly tripling. Pharmacological treatments have evolved with the recent development of glucagon-like peptide 1 agonists, such as semaglutide. However, off-label use of drugs such as Ozempic for cosmetic weight loss has surged in popularity, raising concerns about potential misuse and the emergence of substandard and falsified products in the unregulated supply chain. OBJECTIVE This study aims to conduct a multifactor investigation of product quality and patient safety risks associated with the unregulated online sale of semaglutide by examining product availability and vendor characteristics and assessing product quality through test purchases. METHODS We used a complex risk and quality assessment methodology combining online market surveillance, search engine results page analysis, website content assessment, domain traffic analytics, conducting targeted product test purchases, visual quality inspection of product packaging, microbiological sterility and endotoxin contamination evaluation, and quantitative sample analysis using liquid chromatography coupled with mass spectrometry. RESULTS We collected and evaluated 1080 links from search engine results pages and identified 317 (29.35%) links belonging to online pharmacies, of which 183 (57.7%) led to legal pharmacies and 134 (42.3%) directed users to 59 unique illegal online pharmacy websites. Web traffic data for the period between July and September 2023 revealed that the top 30 domains directly or indirectly affiliated with illegal online pharmacies accumulated over 4.7 million visits. Test purchases were completed from 6 illegal online pharmacies with the highest number of links offering semaglutide products for sale without prescription at the lowest price range. Three injection vial purchases were delivered; none of the 3 Ozempic prefilled injection pens were received due to nondelivery e-commerce scams. All purchased vials were considered probable substandard and falsified products, as visual inspection indicated noncompliance in more than half (59%-63%) of the evaluated criteria. The semaglutide content of samples substantially exceeded labeled amounts by 28.56%-38.69%, although no peptide-like impurities were identified. The lyophilized peptide samples were devoid of viable microorganisms at the time of testing; however, endotoxin was detected in all samples with levels ranging between 2.1645 EU/mg and 8.9511 EU/mg. Furthermore, the measured semaglutide purity was significantly low, ranging between 7.7% and 14.37% and deviating from the 99% claimed on product labels by manufacturers. CONCLUSIONS Glucagon-like peptide 1 agonist drugs promoted for weight loss, similar to erectile dysfunction medications more than 2 decades ago, are becoming the new blockbuster lifestyle medications for the illegal online pharmacy market. Protecting the pharmaceutical supply chain from substandard and falsified weight loss products and raising awareness regarding online medication safety must be a public health priority for regulators and technology platforms alike.
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Affiliation(s)
- Amir Reza Ashraf
- Department of Pharmaceutics, Faculty of Pharmacy, University of Pécs, Pécs, Hungary
| | - Tim Ken Mackey
- Global Health Program, Department of Anthropology, University of California San Diego, La Jolla, CA, United States
| | - Róbert György Vida
- Department of Pharmaceutics, Faculty of Pharmacy, University of Pécs, Pécs, Hungary
| | - Győző Kulcsár
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Pécs, Pécs, Hungary
| | - János Schmidt
- Institute of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Pécs, Hungary
| | - Orsolya Balázs
- Department of Pharmaceutics, Faculty of Pharmacy, University of Pécs, Pécs, Hungary
| | - Bálint Márk Domián
- Department of Pharmaceutics, Faculty of Pharmacy, University of Pécs, Pécs, Hungary
| | - Jiawei Li
- S-3 Research, San Diego, CA, United States
| | - Ibolya Csákó
- Criminal Department, Criminal Directorate, Hungarian National Police Headquarters, Budapest, Hungary
| | - András Fittler
- Department of Pharmaceutics, Faculty of Pharmacy, University of Pécs, Pécs, Hungary
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Community Pharmacy Staff Knowledge, Opinion and Practice toward Drug Shortages in Saudi Arabia. Saudi Pharm J 2022; 29:1383-1391. [PMID: 35002375 PMCID: PMC8720696 DOI: 10.1016/j.jsps.2021.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 09/11/2021] [Indexed: 11/24/2022] Open
Abstract
Drug shortages continue to pose a significant threat to public health and safety. Drug shortages not only worsen patient outcomes, but also significantly burden healthcare systems with additional costs. This study aimed to assess community pharmacy staff knowledge, opinion, and practice toward drug shortages in Saudi Arabia from November 2019 to March 2020. This was a cross-sectional study carried out among 1,008 community pharmacists from Saudi Arabia using a validated, self-administered and Internet-based survey. Analysis was done using chi square and fisher exact tests. Most participants were males (97.2%), less than 30 years old (48.1%), and non-Saudi citizens (94.4%), and 72.0% had good knowledge of drug shortages (score = 4–5). Around 36.0% reported that it takes 1–3 days to receive a response to the shortage report. There was a statistically significant association between the professional level of the community pharmacists and their opinion about reporting drug shortages (P < .05). Most community pharmacies (56.2%) did not receive any notification about drug shortages. In conclusion, most community pharmacists are knowledgeable and have good practice regarding drug shortages, but their opinions about drug shortages differ according to each pharmacy reporting policy.
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Moosivand A, Rangchian M, Zarei L, Peiravian F, Mehralian G, Sharifnia H. An application of multi-criteria decision-making approach to sustainable drug shortages management: evidence from a developing country. J Pharm Health Care Sci 2021; 7:14. [PMID: 33795021 PMCID: PMC8017892 DOI: 10.1186/s40780-021-00200-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 03/03/2021] [Indexed: 11/30/2022] Open
Abstract
Background Drug shortage is a significant public health problem, especially for drugs related to life threatening conditions. Almost all countries affected by variety of supply problems and spent a considerable amount of time and resources responding to shortage. The aim of present study is to determine and prioritize strategies to achieve best solutions for these considerable healthcare system challenges and to evaluate this strategies base on practical criteria. Methods To achieve the study objectives, the research was conducted in two phases. Determining of the strategies to control drug shortage, and comprehensive assessments of priority of possible strategies. For each phase, a self-design questionnaire was developed. The five main managerial strategies dimensions including: regulatory, financial, supply chain, information system and policy-making were set out. Forty-five alternatives were elicited from literature, and were evaluated and trimmed to 37 strategies based on experts’ opinion. The Multiple criteria decision-making (MCDM) methods were applied in second phase. Five important criteria including cost, time, labor, compliance with law and culture were weighed by Analytic Hierarchy Process (AHP) technique. Then, 37 alternatives have been rated base on the five criteria on the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) technique. Results “Creating integrated Supply chain information system to manage medicines inventory in the country”, “Creating and using the databases to predict the shortage of medicines”, “Using track and trace system” are alternatives 20th, 24th and 25th, which related to supply chain (SC) and information system (IS) dimensions have higher priority in the experts’ point of view. The results show IS dimension has 100 percentage of priority; following that policy and supply chain have higher priority, respectively. Conclusion Health systems rely on consistent supplying of pharmaceuticals to support patient care. The results show that information system, policy-making and supply chain are in the top-ranking priorities. Warning system needs to be improved to the advance system via better collaboration with stakeholders, publish precise and explicit national guidelines for drug shortage management, enforce the guidelines, and improve Iran FDA’s pharmaceutical market control capability.
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Affiliation(s)
- Asiye Moosivand
- Department of Pharmacoeconomics and Pharma Management, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Rangchian
- School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Leila Zarei
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Fars, Iran.
| | - Farzad Peiravian
- Department of Pharmacoeconomics and Pharma Management, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gholamhossein Mehralian
- Department of Pharmacoeconomics and Pharma Management, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hesameddin Sharifnia
- Department of Clinical Epidemiology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran
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AlAzmi AA, Jastaniah W, Alhamdan HS, AlYamani AO, AlKhudhyr WI, Abdullah SM, AlZahrani M, AlSahafi A, AlOhali TA, Alkhelawi T, AlObaida Y, Allam A, Al-Hashmi H, Murshid E, AlNajjar F, AlGethami A, AlHarbi A, AlFoheidi MO, AlSaeed AS, Elsolh H, Abosoudah I, Ben Obaid A, AlNahedh M. Addressing Cancer Treatment Shortages in Saudi Arabia: Results of a National Survey and Expert Panel Recommendations. JCO Glob Oncol 2020; 6:476-485. [PMID: 32202921 PMCID: PMC7113076 DOI: 10.1200/jgo.19.00230] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/11/2019] [Indexed: 12/02/2022] Open
Abstract
PURPOSE Cancer treatment shortages are complex and a persistent problem worldwide. Patients with cancer are most vulnerable to drug shortages, which provides opportunities to examine the extent of the challenge(s) facing Saudi Arabia and to provide recommendations toward mitigating the impact of cancer treatment shortages on patient outcomes. MATERIALS AND METHODS A qualitative methodologic approach was conducted in April 2019 using a validated questionnaire and structured panel discussion for data generation. RESULTS Overall, 55 responses were received from practicing oncology health care professionals (26 pharmacists and 29 physicians). The annual average number of treated patients with cancer per institution was 640 (adults [n = 400] and pediatric [n = 240]). All respondents (100%) reported that cancer treatment shortages constitute a current problem in their center, with an average of 5 (range, 1-9) per month. The panelists recognized 2 fundamental points. First, the definition of cancer drug shortages should be standardized and recognized at the national level. Second, the current system must be improved to ensure proper and efficient use of the current resources. On that basis, the panelists developed 9 recommendations for action. CONCLUSION Cancer drug shortage is a significant problem in all health centers in Saudi Arabia. This study presents challenges that should be addressed at the national level and essential consensus recommendations for a coordinated action developed by a panel of experts to tackle the current national problem of cancer treatment shortages. Implementing these recommendations will provide a blueprint for management of national drug shortages in general and cancer treatment shortages in particular.
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Affiliation(s)
- Aeshah A. AlAzmi
- Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Kingdom of Saudi Arabia
- King Abdullah International Medical Research Center, Kingdom of Saudi Arabia
- Department of Clinical Pharmacy, Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
| | - Wasil Jastaniah
- Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Kingdom of Saudi Arabia
- King Abdullah International Medical Research Center, Kingdom of Saudi Arabia
| | - Hani S. Alhamdan
- Pharmaceutical Care Services Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
| | - Arwa O. AlYamani
- Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Kingdom of Saudi Arabia
- King Abdullah International Medical Research Center, Kingdom of Saudi Arabia
- Oncology Quality & Patient Safety, Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
| | | | - Shaker M. Abdullah
- Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
- King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Kingdom of Saudi Arabia
- King Abdullah International Medical Research Center, Kingdom of Saudi Arabia
| | - Mohammed AlZahrani
- Medical Services, Ministry of National Guard Health Affairs, Western Region, Kingdom of Saudi Arabia
| | - Ashraf AlSahafi
- Clinical Services, Ministry of National Guard Health Affairs, Western Region, Kingdom of Saudi Arabia
| | - Tawfiq A. AlOhali
- National Unified Procurement Company, Riyadh, Kingdom of Saudi Arabia
| | - Trad Alkhelawi
- Policy & Market Access in Gulf Cooperation Council, Amgen, Kingdom of Saudi Arabia
| | | | | | - Hani Al-Hashmi
- Oncology Center, King Fahad Specialist Hospital, Dammam, Kingdom of Saudi Arabia
| | - Essam Murshid
- Department of Medical/Radiation Oncology, Prince Sultan Medical Military City, Riyadh, Kingdom of Saudi Arabia
| | - Fouad AlNajjar
- Pharmaceutical Care Services Department, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
| | - Ashwag AlGethami
- Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
- Department of Clinical Pharmacy, Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
| | - Atika AlHarbi
- Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
- Department of Clinical Pharmacy, Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
| | - Meteb O. AlFoheidi
- Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
- Saudi Oncology Society, Riyadh, Kingdom of Saudi Arabia
| | - Ahmad S. AlSaeed
- Princess Noorah Oncology Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
- Saudi Scientific Society of Blood and Marrow Transplantation, Riyadh, Kingdom of Saudi Arabia
| | - Hassan Elsolh
- Medical Affairs, King Faisal Specialist Hospital & Research Center, Riyadh, Kingdom of Saudi Arabia
| | - Ibraheem Abosoudah
- King Faisal Specialist Hospital & Research Center, Jeddah, Kingdom of Saudi Arabia
- Saudi Arabian Pediatric Hematology Oncology Society, Riyadh, Kingdom of Saudi Arabia
| | - Abdulaziz Ben Obaid
- Pharmaceutical Care Services Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
- Saudi Oncology Pharmacy Assembly, Riyadh, Kingdom of Saudi Arabia
| | - Mohammed AlNahedh
- Department of Pharmaceutical Care, Oncology Pharmacy Services, King Faisal Specialist Hospital & Research Center, Riyadh, Kingdom of Saudi Arabia
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Martei YM, Grover S, Bilker WB, Monare B, Setlhako DI, Ralefala TB, Manshimba P, Gross R, Shulman LN, DeMichele A. Impact of Essential Medicine Stock Outs on Cancer Therapy Delivery in a Resource-Limited Setting. J Glob Oncol 2019; 5:1-11. [PMID: 30969808 PMCID: PMC6528733 DOI: 10.1200/jgo.18.00230] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/19/2019] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Essential cancer medicine stock outs are occurring at an increasing frequency worldwide and represent a potential barrier to delivery of standard therapy in patients with cancer in low- and middle-income countries. The objective of this study was to measure the impact of cancer medicine stock outs on delivery of optimal therapy in Botswana. METHODS We conducted a retrospective analysis of patients with common solid tumor malignancies who received systemic cancer therapy in 2016 at Princess Marina Hospital, Gaborone, Botswana. Primary exposure was the duration of cancer medicine stock out during a treatment cycle interval, when the cancer therapy was intended to be administered. Mixed-effects univariable and multivariable logistic regression analyses were used to calculate the association of the primary exposure, with the primary outcome, suboptimal therapy delivery, defined as any dose reduction, dose delay, missed cycle, or switch in intended therapy. RESULTS A total of 378 patients met diagnostic criteria and received systemic chemotherapy in 2016. Of these, 76% received standard regimens consisting of 1,452 cycle intervals and were included in this analysis. Paclitaxel stock out affected the highest proportion of patients. In multivariable mixed-effects logistic regression, each week of any medicine stock out (odds ratio, 1.9; 95% CI, 1.7 to 2.13; P < .001) was independently associated with an increased risk of a suboptimal therapy delivery event. CONCLUSION Each week of cancer therapy stock out poses a substantial barrier to receipt of high-quality cancer therapy in low- and middle-income countries. A concerted effort between policymakers and cancer specialists is needed to design implementation strategies to build sustainable systems promoting a reliable supply of cancer medicines.
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Affiliation(s)
| | - Surbhi Grover
- University of Pennsylvania, Philadelphia, PA
- Botswana University of Pennsylvania Partnership, Gaborone, Botswana
| | | | - Barati Monare
- Botswana University of Pennsylvania Partnership, Gaborone, Botswana
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Nonzee NJ, Luu TH. The Drug Shortage Crisis in the United States: Impact on Cancer Pharmaceutical Safety. Cancer Treat Res 2019; 171:75-92. [PMID: 30552658 DOI: 10.1007/978-3-319-43896-2_6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Drug shortages pose a significant public health concern in the United States, and cancer drugs are among those most affected. Shortages present serious safety risks for patients and substantial burden on providers and the healthcare system. Multifaceted drivers of this complex problem include manufacturing disruptions, raw material shortages, regulatory issues, market dynamics, and limited financial incentives that reward quality and production of off-patent drugs. Oncology drugs in short supply have resulted in substitution of less effective or more toxic alternatives, medication errors, and treatment delays, and are especially concerning for medications with no adequate substitute. Consequently, patient outcomes such as disease progression and survival have been adversely affected. Furthermore, emerging gray markets have contributed to cost-prohibitive markups and introduction of counterfeit products that compromise patient safety. The Food and Drug Administration plays a key role in preventing and managing pharmaceutical shortages, largely through regulations requiring early notification of manufacturing interruptions. Other proposed strategies similarly target upstream causes and center on reducing regulatory hurdles for manufacturers and increasing incentives for market entry and quality improvement. Despite progress in preventing supply disruptions, continued exploration of underlying systemic drivers remains critical to informing long-term solutions and alleviating the clinical and economic impact of drug shortages.
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Affiliation(s)
- Narissa J Nonzee
- Department of Health Policy and Management, University of California, Los Angeles, CA, USA.
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Fittler A, Vida RG, Rádics V, Botz L. A challenge for healthcare but just another opportunity for illegitimate online sellers: Dubious market of shortage oncology drugs. PLoS One 2018; 13:e0203185. [PMID: 30153304 PMCID: PMC6112670 DOI: 10.1371/journal.pone.0203185] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2017] [Accepted: 06/20/2018] [Indexed: 12/18/2022] Open
Abstract
Introduction Drug shortages mean a challenge to healthcare systems. Exposed patients or health care providers may seek alternative resources for these products online. The purpose of our study was to analyze the online availability of oncology shortage drugs at national and at international levels in 2014 and 2016. Methods We tested the online accessibility of oncology shortage drugs by simulating the Internet search method of patients. Search results were evaluated according to operational, distributional, and patient safety characteristics. Results In 2014 and 2016 all (100%) antineoplastic agents affected by shortages were available on the Internet without medical prescription. The number of relevant websites among search engine results has decreased from 112 to 98, while online vendors actually offering oncology shortage drugs for sale has risen from 66.1% to 80.6% within relevant websites in the two evaluated years. None of the online sellers were classified as legitimate or accredited by LegitScript and VIPPS online pharmacy verification databases. Conclusion According to our findings shortage oncology drugs are widely available online. To manage shortages and illegal Internet trade national and international standardized shortage reporting and information systems, regularly updated Internet pharmacy verification databases are needed. As well, institutional procurement and medication use review policies are required.
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Affiliation(s)
- András Fittler
- Department of Pharmaceutics and Central Clinical Pharmacy, Faculty of Pharmacy, University of Pécs, Pécs, Hungary
- * E-mail:
| | - Róbert György Vida
- Department of Pharmaceutics and Central Clinical Pharmacy, Faculty of Pharmacy, University of Pécs, Pécs, Hungary
| | - Valter Rádics
- Department of Pharmaceutics and Central Clinical Pharmacy, Faculty of Pharmacy, University of Pécs, Pécs, Hungary
| | - Lajos Botz
- Department of Pharmaceutics and Central Clinical Pharmacy, Faculty of Pharmacy, University of Pécs, Pécs, Hungary
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Diagnosis and treatment of bronchiolitis obliterans syndrome accessible universally. Bone Marrow Transplant 2018; 54:383-392. [PMID: 30038355 DOI: 10.1038/s41409-018-0266-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 05/23/2018] [Accepted: 06/07/2018] [Indexed: 12/17/2022]
Abstract
The incidence of bronchiolitis obliterans syndrome (BOS), a devastating manifestation of chronic graft-versus-host-disease, may rise globally due to steady increases in utilization of allogeneic hematopoietic cell transplantation (HCT). Though some advances have occurred in the past decade regarding understanding of the pathogenesis, diagnosis and treatment of BOS, the overall mortality and morbidity remain very high. We sought to determine the current diagnostic and therapeutic challenges, which can potentially hinder optimal management of BOS both in developed and developing countries. We performed a comprehensive systematic review of both modern diagnostic modalities and treatments and then assessed which of them would be universally accessible. The 2014 National Institutes of Health chronic GVHD criteria remains the gold standard tool for diagnosing BOS. Important elements of treatment involve early and accurate detection, as well as utilizing the treatment modalities with known (but variable efficacy) e.g. fluticasone-azithromycin-montelukast [FAM] combination, etanercept, extra-corporeal photopheresis [ECP], lung transplantation, and prompt treatment of complications including infections in sufferers of BOS. Our results indicate that optimum diagnostic tools are not readily available in some parts of the world for early detection, which include a lack of CT scanners, unavailability of pulmonary function testing tools, absence of sub-specialists, lack of certain effective treatments and late referral for lung transplant. We present a systematic review of current literature along with recommendations for available therapies to guide practitioners to optimize the long-term outcomes in HCT survivors regardless of access to experts and expensive therapies.
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Thornburg CK, Walter T, Walker KD. Biocatalysis of a Paclitaxel Analogue: Conversion of Baccatin III to N-Debenzoyl-N-(2-furoyl)paclitaxel and Characterization of an Amino Phenylpropanoyl CoA Transferase. Biochemistry 2017; 56:5920-5930. [DOI: 10.1021/acs.biochem.7b00912] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Chelsea K. Thornburg
- Department of Chemistry and ‡Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, United States
| | - Tyler Walter
- Department of Chemistry and ‡Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, United States
| | - Kevin D. Walker
- Department of Chemistry and ‡Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, United States
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Beck JC, Chen B, Gordon BG. Physician approaches to drug shortages: Results of a national survey of pediatric hematologist/oncologists. World J Clin Oncol 2017; 8:336-342. [PMID: 28848700 PMCID: PMC5554877 DOI: 10.5306/wjco.v8.i4.336] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 05/04/2017] [Accepted: 07/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate personnel involved in scarce drug prioritization and distribution and the criteria used to inform drug distribution during times of shortage among pediatric hematologists/oncologists.
METHODS Using the American Society of Pediatric Hematology/Oncology (ASPHO) membership list, a 20 question survey of pediatric hematologists/oncologists was conducted via email to evaluate personnel involved in scarce drug prioritization and distribution and criteria used to inform scarce drug distribution.
RESULTS Nearly 65% of the 191 study respondents had patients directly affected by drug shortages. Most physicians find out about shortages from the pharmacist (n = 179, 98%) or other doctors (n = 75, 41%). One third of respondents do not know if there is a program or policy for handling drug shortages at their institution. The pharmacist was the most commonly cited decision maker for shortage drug distribution (n = 128, 70%), followed by physicians (n = 109, 60%). One fourth of respondents did not know who makes decisions about shortage drug distribution at their institution. The highest priority criterion among respondents was use of the shortage drug for curative, rather than palliative intent and lowest priority criterion was order of arrival or first-come first-served.
CONCLUSION Despite pediatric hematology/oncology physicians and patients being heavily impacted by drug shortages, institutional processes for handling shortages are lacking. There is significant disparity between how decisions for distribution of shortage drugs are currently made and how study respondents felt those decisions should be made. An institution-based, and more importantly, a societal approach to drug shortages is necessary to reconcile these disparities.
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Jecker NS, Wightman AG, Rosenberg AR, Diekema DS. From protection to entitlement: selecting research subjects for early phase clinical trials involving breakthrough therapies. JOURNAL OF MEDICAL ETHICS 2017; 43:391-400. [PMID: 28408724 DOI: 10.1136/medethics-2016-103868] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 01/25/2017] [Accepted: 02/13/2017] [Indexed: 06/07/2023]
Abstract
Our goals are to (1) set forth and defend a multiprinciple system for selecting individuals who meet trial eligibility criteria to participate in early phase clinical trials testing chimeric antigen receptor (CAR T-cell) for acute lymphoblastic leukaemia when demand for participation exceeds spaces available in a trial; (2) show the relevance of these selection criteria to other breakthrough experimental therapies; (3) argue that distinct distributive justice criteria apply to breakthrough experimental therapies, standard research and healthcare and (4) argue that as evidence of benefit increases, the emphasis of justice in research shifts from protecting subjects from harm to ensuring fair access to benefits.
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Affiliation(s)
- Nancy S Jecker
- University of Washington School of Medicine, Department of Bioethics & Humanities, Seattle, Washington, USA
| | - Aaron G Wightman
- University of Washington School of Medicine, Department of Pediatrics and Seattle Children's Hospital, Division of Nephrology, Seattle, Washington, USA
| | - Abby R Rosenberg
- University of Washington School of Medicine, Department of Pediatrics and Seattle Children's Hospital, Division of Hematology-Oncology, Seattle, Washington, USA
| | - Douglas S Diekema
- University of Washington Department of Pediatrics and Seattle Children's Hospital, Division of Emergency Medicine, Seattle, Washington, USA
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12
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Abstract
The practices of group purchasing organizations have been recently highlighted by several sources as a potential major root cause of generic chemotherapy drug shortages.
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13
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de Lemos ML, Waignein S, de Haan M. Evidence-based practice in times of drug shortage. J Oncol Pharm Pract 2015; 22:566-70. [DOI: 10.1177/1078155215589980] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Shortage of oncology drugs is a particularly complicated issue because there are usually limited therapeutic options. Moreover, oncology practice may employ medications for supportive indications which differ from their main usage. This means shortage of oncology drugs is not usually addressed by the major drug shortage guidelines. We have previously shown that, during a shortage crisis, it is possible to make a recommendation on the use of an expired drug supply based on a reasonable estimate of its safety and efficacy. Here, we would like to share further examples on how to deduce potential therapeutic alternatives based on pharmacokinetic and pharmacodynamic principles in the absence of direct clinical evidence in the literature.
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Affiliation(s)
- Mário L. de Lemos
- Provincial Pharmacy, Systemic Therapy Program, BC Cancer Agency, Vancouver, BC V5Z 1H5, Canada
| | - Sally Waignein
- Provincial Pharmacy, Systemic Therapy Program, BC Cancer Agency, Vancouver, BC V5Z 1H5, Canada
| | - Marie de Haan
- Provincial Pharmacy, Systemic Therapy Program, BC Cancer Agency, Vancouver, BC V5Z 1H5, Canada
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14
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Goodman E, Bernhardt MB, Li Y, Aplenc R, Adamson PC. The impact of chemotherapy shortages on COG and local clinical trials: a report from the Children's Oncology Group. Pediatr Blood Cancer 2015; 62:940-4. [PMID: 25704486 PMCID: PMC4670038 DOI: 10.1002/pbc.25445] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Accepted: 12/02/2014] [Indexed: 12/15/2022]
Abstract
BACKGROUND Oncology drug shortage is associated with increased patient adverse events and decreased enrollment on clinical trials for adult patients; however, the impact of oncology drug shortages has not been well studied in children with cancer. PROCEDURE The Children's Oncology Group (COG) distributed a 5-item survey to 226 COG site-specific principal investigators (PI's) and 14-item survey to 161 COG pharmacists to gather data the impact of chemotherapeutic shortages on clinical trials and patient care. RESULTS The response rate was 66.4% (150/226) for PI's and 29.8% (48/161) for pharmacists. COG PI's reported daunorubicin (73%), methotrexate (56%), asparaginase/PEG-asparaginase (42%), doxorubicin (26%), thiotepa (21%), and cytarabine (20%) were most commonly in shortage, while COG pharmacists reported daunorubicin (80%), methotrexate (66%), vincristine (21%), thiotepa (41%), asparaginase/PEG-asparaginase (34%), and cytarabine (34%) were most commonly in shortage over the past two years. Pharmacists were twice as likely to report a shortage compared with PI's (OR 2.1, 95% CI: 1.6-2.7, P < 0.0001). Fifty percent (74/147) of COG PI's reported at least one patient enrolled on a clinical trial was impacted by drug shortage, and 66% (98/148) of COG PI's reported at least one patient had clinical care impacted by drug shortage. CONCLUSIONS Chemotherapy shortages remain widespread across institutions, hinder clinical trials, and may contribute to adverse events in children with cancer. The increased frequency of chemotherapy shortages reported by pharmacists suggests that pharmacist efforts may mitigate negative impact chemotherapy shortages. Over half of pediatric institutions are implementing recommendations to address shortages, such as cross-institutional collaboration and center-level guidelines.
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Affiliation(s)
- Elizabeth Goodman
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania,Correspondence to: Elizabeth K. Goodman, AB, Perelman School of Medicine, University of Pennsylvania, 3501 Civic Center Blvd, CTRB 4200, Philadelphia, PA 19146, Tel: 267-426-7252,
| | | | - Yimei Li
- Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania,Department of Biostatistics, University of Pennsylvania
| | - Richard Aplenc
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Peter C. Adamson
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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15
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Kehl KL, Gray SW, Kim B, Kahn KL, Haggstrom D, Roudier M, Keating NL. Oncologists' experiences with drug shortages. J Oncol Pract 2015; 11:e154-62. [PMID: 25549653 PMCID: PMC4371121 DOI: 10.1200/jop.2014.000380] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
PURPOSE There have been numerous reports of shortages of injectable drugs for cancer in the last decade. We assessed physician experiences with drug shortages in a population-based cohort of medical oncologists caring for patients with lung or colorectal cancer. METHODS We surveyed medical oncologists caring for patients with lung or colorectal cancer in the Cancer Care Outcomes Research and Surveillance Consortium from 2012 to 2013 (participation rate, 53%). Oncologists reported experiences with shortages of leucovorin, fluorouracil, dexamethasone, cyanocobalamin, paclitaxel, cisplatin, and etoposide in the prior year and whether they had used a less-effective alternative because of a shortage. We used multivariable logistic regression to assess for associations between physician or practice characteristics and encountering shortages. RESULTS Among 330 respondents, 74% reported experiences with a shortage of at least one drug in our survey, and 28% reported using a less-effective alternative because of a shortage. Although physician demographic characteristics did not predict reports of drug shortages, practice characteristics did. Veterans Affairs (VA) oncologists were less likely to report experiencing any shortage than oncologists in single-specialty group practice (odds ratio [OR], 0.4; 95% CI, 0.2 to 0.9). The reported use of a less effective alternative to any drug was also less common among VA oncologists (OR, 0.3; 95% CI, 0.1 to 0.9) and oncologists affiliated with health maintenance organizations (OR, 0.4; 95% CI, 0.2 to 0.9) compared with physicians in single-specialty groups. CONCLUSION Most oncologists encountered drug shortages in the year before our survey, but experiences with shortages varied with practice structure. Further research is needed to quantitatively assess the impact of drug shortages on patients and evaluate various strategies for managing them.
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Affiliation(s)
- Kenneth L Kehl
- The University of Texas MD Anderson Cancer Center, Houston, TX; Dana-Farber Cancer Institute; Frontier Science & Technology Research Foundation; Harvard Medical School; Brigham and Women's Hospital, Boston, MA; University of California San Francisco, San Francisco; University of California Los Angeles, Los Angeles; RAND Corporation, Santa Monica, CA; Veterans Affairs (VA) Health Services Research & Development, Roudebush VA; and Indiana University School of Medicine, Indianapolis, IN
| | - Stacy W Gray
- The University of Texas MD Anderson Cancer Center, Houston, TX; Dana-Farber Cancer Institute; Frontier Science & Technology Research Foundation; Harvard Medical School; Brigham and Women's Hospital, Boston, MA; University of California San Francisco, San Francisco; University of California Los Angeles, Los Angeles; RAND Corporation, Santa Monica, CA; Veterans Affairs (VA) Health Services Research & Development, Roudebush VA; and Indiana University School of Medicine, Indianapolis, IN
| | - Benjamin Kim
- The University of Texas MD Anderson Cancer Center, Houston, TX; Dana-Farber Cancer Institute; Frontier Science & Technology Research Foundation; Harvard Medical School; Brigham and Women's Hospital, Boston, MA; University of California San Francisco, San Francisco; University of California Los Angeles, Los Angeles; RAND Corporation, Santa Monica, CA; Veterans Affairs (VA) Health Services Research & Development, Roudebush VA; and Indiana University School of Medicine, Indianapolis, IN
| | - Katherine L Kahn
- The University of Texas MD Anderson Cancer Center, Houston, TX; Dana-Farber Cancer Institute; Frontier Science & Technology Research Foundation; Harvard Medical School; Brigham and Women's Hospital, Boston, MA; University of California San Francisco, San Francisco; University of California Los Angeles, Los Angeles; RAND Corporation, Santa Monica, CA; Veterans Affairs (VA) Health Services Research & Development, Roudebush VA; and Indiana University School of Medicine, Indianapolis, IN
| | - David Haggstrom
- The University of Texas MD Anderson Cancer Center, Houston, TX; Dana-Farber Cancer Institute; Frontier Science & Technology Research Foundation; Harvard Medical School; Brigham and Women's Hospital, Boston, MA; University of California San Francisco, San Francisco; University of California Los Angeles, Los Angeles; RAND Corporation, Santa Monica, CA; Veterans Affairs (VA) Health Services Research & Development, Roudebush VA; and Indiana University School of Medicine, Indianapolis, IN
| | - Maryse Roudier
- The University of Texas MD Anderson Cancer Center, Houston, TX; Dana-Farber Cancer Institute; Frontier Science & Technology Research Foundation; Harvard Medical School; Brigham and Women's Hospital, Boston, MA; University of California San Francisco, San Francisco; University of California Los Angeles, Los Angeles; RAND Corporation, Santa Monica, CA; Veterans Affairs (VA) Health Services Research & Development, Roudebush VA; and Indiana University School of Medicine, Indianapolis, IN
| | - Nancy L Keating
- The University of Texas MD Anderson Cancer Center, Houston, TX; Dana-Farber Cancer Institute; Frontier Science & Technology Research Foundation; Harvard Medical School; Brigham and Women's Hospital, Boston, MA; University of California San Francisco, San Francisco; University of California Los Angeles, Los Angeles; RAND Corporation, Santa Monica, CA; Veterans Affairs (VA) Health Services Research & Development, Roudebush VA; and Indiana University School of Medicine, Indianapolis, IN
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16
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Costelloe EM, Guinane M, Nugent F, Halley O, Parsons C. An audit of drug shortages in a community pharmacy practice. Ir J Med Sci 2014; 184:435-40. [PMID: 24859372 DOI: 10.1007/s11845-014-1139-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Accepted: 05/05/2014] [Indexed: 11/24/2022]
Abstract
BACKGROUND There are no firm data on drug shortages in Irish community pharmacy. This prospective observational study aimed to characterise the drug shortage problem in an Irish community pharmacy. AIMS The primary aim was to determine numbers and durations of drug shortages. Secondary aims included comparing these shortages with Irish Pharmacy Union (IPU) drug shortage lists and determining the frequency with which notifications were received prior to shortages. Further secondary aims were to examine relationships between causes of drug shortages and drug costs and between causes of drug shortages and shortage durations. METHODS The study took place in a community pharmacy in a Limerick City suburb between October 2012 and February 2013. Data were collected daily regarding drugs that were dispensed, but unavailable to purchase. Suppliers/manufacturers provided data on the reasons for shortages. RESULTS 65/1,232 dispensed drugs (5.3%) were in short supply over the study period. Median shortage duration was 13 days (interquartile range 4-32 days) and median cost was <euro>8.10. Numbers of unavailable drugs by month varied from 13 to 38. Monthly IPU drug shortage lists identified between six and eight of these shortages depending on the month. Two notifications were received from suppliers/manufacturers regarding shortages. Parallel exports had the highest mean costs (mean <euro>38.05) and manufacturing problems were associated with the longest durations (mean 57.44 days). CONCLUSIONS This study highlights the drug shortage problem in an Irish community pharmacy. We propose that enhanced communication between all stakeholders is the most worthwhile solution. Further studies are needed.
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17
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McKeever AE, Bloch JR, Bratic A. Drug shortages and the burden of access to care: a critical issue affecting patients with cancer. Clin J Oncol Nurs 2014; 17:490-5. [PMID: 24080048 DOI: 10.1188/13.cjon.490-495] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Pharmaceutical drug shortages are multifaceted and complex problems that affect all aspects of health care, including patients, caregivers, healthcare providers, third-party payers, the pharmaceutical industry, and regulators. Drug shortages have increased significantly since 2000, which cause increases in healthcare costs and compromised patient care. New government regulations have led the U.S. Food and Drug Administration to focus efforts on updating policies and improving regulation of the pharmaceutical industry to limit and avoid drug shortages. This article discusses the current issues surrounding the pharmaceutical drug shortage and the implications for patients and healthcare providers. A review of the literature presents the multidimensional impact of the pharmaceutical drug shortage, and the analysis shows patients who are most burdened by drug shortages and have experienced substandard care, increased cost of care, and compromised quality of health care.
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Affiliation(s)
- Amy E McKeever
- College of Nursing, Villanova University in Pennsylvania
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18
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DeCamp M, Joffe S, Fernandez CV, Faden RR, Unguru Y. Chemotherapy drug shortages in pediatric oncology: a consensus statement. Pediatrics 2014; 133:e716-24. [PMID: 24488741 PMCID: PMC3934344 DOI: 10.1542/peds.2013-2946] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Shortages of essential drugs, including critical chemotherapy drugs, have become commonplace. Drug shortages cost significant time and financial resources, lead to adverse patient outcomes, delay clinical trials, and pose significant ethical challenges. Pediatric oncology is particularly susceptible to drug shortages, presenting an opportunity to examine these ethical issues and provide recommendations for preventing and alleviating shortages. We convened the Working Group on Chemotherapy Drug Shortages in Pediatric Oncology (WG) and developed consensus on the core ethical values and practical actions necessary for a coordinated response to the problem of shortages by institutions, agencies, and other stakeholders. The interdisciplinary and multiinstitutional WG included practicing pediatric hematologist-oncologists, nurses, hospital pharmacists, bioethicists, experts in emergency management and public policy, legal scholars, patient/family advocates, and leaders of relevant professional societies and organizations. The WG endorsed 2 core ethical values: maximizing the potential benefits of effective drugs and ensuring equitable access. From these, we developed 6 recommendations: (1) supporting national polices to prevent shortages, (2) optimizing use of drug supplies, (3) giving equal priority to evidence-based uses of drugs whether they occur within or outside clinical trials, (4) developing an improved clearinghouse for sharing drug shortage information, (5) exploring the sharing of drug supplies among institutions, and (6) developing proactive stakeholder engagement strategies to facilitate prevention and management of shortages. Each recommendation includes an ethical rationale, action items, and barriers that must be overcome. Implemented together, they provide a blueprint for effective and ethical management of drug shortages in pediatric oncology and beyond.
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Affiliation(s)
- Matthew DeCamp
- Johns Hopkins Berman Institute of Bioethics, Baltimore, Maryland;,Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Steven Joffe
- Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Conrad V. Fernandez
- Division of Pediatric Hematology/Oncology, IWK Health Centre and Dalhousie University, Halifax, Nova Scotia; and
| | - Ruth R. Faden
- Johns Hopkins Berman Institute of Bioethics, Baltimore, Maryland
| | - Yoram Unguru
- Johns Hopkins Berman Institute of Bioethics, Baltimore, Maryland;,Division of Pediatric Hematology/Oncology, The Herman and Walter Samuelson Children’s Hospital at Sinai, Baltimore, Maryland
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19
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Denburg AE, Knaul FM, Atun R, Frazier LA, Barr RD. Beyond the bench and the bedside: economic and health systems dimensions of global childhood cancer outcomes. Pediatr Blood Cancer 2014; 61:572-6. [PMID: 24249518 DOI: 10.1002/pbc.24858] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 10/18/2013] [Indexed: 11/11/2022]
Abstract
Globally, the number of new cases of childhood cancer continues to rise, with a widening gulf in outcomes across countries, despite the availability of effective cure options for many pediatric cancers. Economic forces and health system realities are deeply embedded in the foundation of disparities in global childhood cancer outcomes. A truly global effort to close the childhood cancer divide therefore requires systemic solutions. Analysis of the economic and health system dimensions of childhood cancer outcomes is essential to progress in childhood cancer survival around the globe. The conceptual power of this approach is significant. It provides insight into how and where pediatric oncology entwines with broader political and economic conditions, and highlights the mutual benefit derived from systems-oriented solutions.
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Affiliation(s)
- Avram E Denburg
- Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada; Dana-Farber Children's Cancer Center, Boston, Massachusetts; Harvard Global Equity Initiative, Harvard University, Boston, Massachusetts; Harvard Medical School, Harvard University, Boston, Massachusetts
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20
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St Germain D, Denicoff AM, Dimond EP, Carrigan A, Enos RA, Gonzalez MM, Wilkinson K, Mathiason MA, Duggan B, Einolf S, McCaskill-Stevens W, Bryant DM, Thompson MA, Grubbs SS, Go RS. Use of the National Cancer Institute Community Cancer Centers Program screening and accrual log to address cancer clinical trial accrual. J Oncol Pract 2014; 10:e73-80. [PMID: 24424313 PMCID: PMC3948711 DOI: 10.1200/jop.2013.001194] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Screening logs have the potential to help oncology clinical trial programs at the site level, as well as trial leaders, address enrollment in real time. Such an approach could be especially helpful in improving representation of racial/ethnic minority and other underrepresented populations in clinical trials. METHODS The National Cancer Institute Community Cancer Centers Program (NCCCP) developed a screening log. Log data collected from March 2009 through May 2012 were analyzed for number of patients screened versus enrolled, including for demographic subgroups; screening methods; and enrollment barriers, including reasons for ineligibility and provider and patient reasons for declining to offer or participate in a trial. User feedback was obtained to better understand perceptions of log utility. RESULTS Of 4,483 patients screened, 18.4% enrolled onto NCCCP log trials. Reasons for nonenrollment were ineligibility (51.6%), patient declined (25.8%), physician declined (15.6%), urgent need for treatment (6.6%), and trial suspension (0.4%). Major reasons for patients declining were no desire to participate in trials (43.2%) and preference for standard of care (39%). Major reasons for physicians declining to offer trials were preference for standard of care (53%) and concerns about tolerability (29.3%). Enrollment rates onto log trials did not differ between white and black (P = .15) or between Hispanic and non-Hispanic patients (P = .73). Other races had lower enrollment rates than whites and blacks. Sites valued the ready access to log data on enrollment barriers, with some sites changing practices to address those barriers. CONCLUSION Use of screening logs to document enrollment barriers at the local level can facilitate development of strategies to enhance clinical trial accrual.
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Affiliation(s)
- Diane St Germain
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Andrea M. Denicoff
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Eileen P. Dimond
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Angela Carrigan
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Rebecca A. Enos
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Maria M. Gonzalez
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Kathy Wilkinson
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Michelle A. Mathiason
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Brenda Duggan
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Shaun Einolf
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Worta McCaskill-Stevens
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Donna M. Bryant
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Michael A. Thompson
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Stephen S. Grubbs
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
| | - Ronald S. Go
- National Cancer Institute, Bethesda; SAIC-Frederick, Frederick National Laboratory for Cancer Research, Frederick; The EMMES Corporation, Rockville, MD; St Joseph Hospital of Orange, Orange, CA; Billings Clinic Cancer Center, Billings, MT; Gundersen Health System, La Crosse; Waukesha Memorial Hospital (ProHealth Care), Waukesha, WI; The Cancer Program of Our Lady of the Lake and Mary Bird Perkins Cancer Center, Baton Rouge, LA; Delaware Cancer Consortium, Dover; Helen F. Graham Cancer Center, Newark, DE
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Jagsi R, Spence R, Rathmell WK, Bradbury A, Peppercorn J, Grubbs S, Moy B. Ethical considerations for the clinical oncologist in an era of oncology drug shortages. Oncologist 2014; 19:186-92. [PMID: 24449096 DOI: 10.1634/theoncologist.2013-0301] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Shortages of injectable drugs affect many cancer patients and providers in the U.S. today. Scholars and policymakers have recently begun to devote increased attention to these issues, but only a few tangible resources exist to guide clinical oncologists in developing strategies for dealing with drug shortages on a recurring basis. This article discusses existing information from the scholarly literature, policy analyses, and other relevant sources and seeks to provide practical ethical guidance to the broad audience of oncology professionals who are increasingly confronted with such cases in their practice. We begin by providing a brief overview of the history, causes, and regulatory context of oncology drug shortages in the U.S., followed by a discussion of ethical frameworks that have been proposed in this setting. We conclude with practical recommendations for ethical professional behavior in these increasingly common and challenging situations.
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Affiliation(s)
- Reshma Jagsi
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA; American Society of Clinical Oncology, Alexandria, Virginia, USA; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; University of Pennsylvania, Philadelphia, Pennsylvania USA; Duke University, Durham, North Carolina, USA; Medical Oncology Hematology Consultants, Newark, Delaware, USA; Massachusetts General Hospital, Boston, Massachusetts, USA
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23
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Kantarjian H, Zwelling L. Cancer drug prices and the free-market forces. Cancer 2013; 119:3903-5. [DOI: 10.1002/cncr.28330] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2013] [Revised: 07/24/2013] [Accepted: 07/30/2013] [Indexed: 11/05/2022]
Affiliation(s)
- Hagop Kantarjian
- Department of Leukemia; Division of Cancer Medicine; The University of Texas MD Anderson Cancer Center; Houston Texas
| | - Leonard Zwelling
- Department of Experimental Therapeutics; The University of Texas MD Anderson Cancer Center; Houston Texas
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Mehta PS, Wiernikowski JT, Petrilli JAS, Barr RD. Essential medicines for pediatric oncology in developing countries. Pediatr Blood Cancer 2013; 60:889-91. [PMID: 23450774 DOI: 10.1002/pbc.24476] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Accepted: 12/26/2012] [Indexed: 11/11/2022]
Abstract
The burden of cancer in children in low and middle income countries (LMICs) is substantial, comprising at least 80% of incident cases globally, and an even higher proportion of cancer-related deaths. With survival rates exceeding 80% in high income countries, it is imperative to transfer these successes to LMICs. A major challenge is the poor availability of safe, cost-effective chemotherapy. A list of 51 drugs-chemotherapeutics, infectious disease agents, and supportive care medications-is proposed as essential to improving the survival of children with cancer in LMICs with an additional 13 drugs identified as being of further value.
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Affiliation(s)
- Parth S Mehta
- Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77094, USA.
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McBride A, Holle LM, Westendorf C, Sidebottom M, Griffith N, Muller RJ, Hoffman JM. National survey on the effect of oncology drug shortages on cancer care. Am J Health Syst Pharm 2013; 70:609-17. [DOI: 10.2146/ajhp120563] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- Ali McBride
- Department of Pharmacy, The James Cancer Hospital and Solove Research Institute and The Ohio State University, Columbus
| | - Lisa M. Holle
- School of Pharmacy, University of Connecticut, Storrs
| | - Colleen Westendorf
- St. Jude Children’s Research Hospital, Memphis, TN; at the time of writing she was Oncology Pharmacy Resident, University of Kentucky, Lexington
| | | | - Niesha Griffith
- The James Cancer Hospital and Solove Research Institute and The Ohio State University, Columbus
| | - Raymond J. Muller
- Division of Pharmacy Services, Memorial Sloan Kettering Cancer Center, New York, NY
| | - James M. Hoffman
- Pharmaceutical Services, and Associate Member, Pharmaceutical Sciences, St. Jude Children’s Research Hospital, and Associate Professor of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis
- Department of Pharmacy, The James Cancer Hospital and Solove Research Institute and The Ohio State University, Columbus
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26
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Patel S, Liedtke M, Ngo D, Medeiros BC. A single-center experience of the nationwide daunorubicin shortage: substitution with doxorubicin in adult acute lymphoblastic leukemia. Leuk Lymphoma 2013; 54:2231-5. [DOI: 10.3109/10428194.2013.772606] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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27
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Affiliation(s)
- Michael P. Link
- From the American Society of Clinical Oncology, Alexandria, VA
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28
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Unguru Y, Joffe S, Fernandez CV, Yu AL. Ethical issues for control-arm patients after revelation of benefits of experimental therapy: a framework modeled in neuroblastoma. J Clin Oncol 2013; 31:641-6. [PMID: 23295797 PMCID: PMC3565183 DOI: 10.1200/jco.2012.47.1227] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
In 2009, the Children's Oncology Group (COG) phase III randomized controlled trial, ANBL0032, found that adding immunotherapy (Ch14.18) to standard therapy significantly improved outcomes in patients with high-risk neuroblastoma when administered within 110 days after autologous stem-cell transplantation (SCT). After careful deliberation and consultation, the COG Neuroblastoma Committee decided to offer Ch14.18 to prior trial participants who had been randomly assigned to the control arm (no immunotherapy), regardless of the time that had elapsed since SCT. This decision occurred in the context of a limited supply of Ch14.18 and no data regarding its role when administered beyond 110 days. In this article, we analyze the numerous ethical challenges highlighted by the ANBL0032 trial, including the limits of researchers' reciprocity-based obligations to study participants, post-trial access to beneficial therapies, and the balance between scientific knowledge and parental hope. These deliberations may be useful to other researchers when considering their ethical obligations to control-arm participants in the wake of a positive randomized trial.
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Affiliation(s)
- Yoram Unguru
- Division of Pediatric Hematology/Oncology, The Herman and Walter Samuelson Children's Hospital at Sinai, 2401 West Belvedere Ave, Baltimore, MD 21215-5271, USA.
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29
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Neglected infectious diseases: are push and pull incentive mechanisms suitable for promoting drug development research? HEALTH ECONOMICS POLICY AND LAW 2013; 8:185-208. [PMID: 23343639 PMCID: PMC3592259 DOI: 10.1017/s1744133112000321] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Infectious diseases are among the main causes of death and disability in developing countries, and they are a major reason for the health disparity between rich and poor countries. One of the reasons for this public health tragedy is a lack of lifesaving essential medicines, which either do not exist or badly need improvements. In this article, we analyse which of the push and pull mechanisms proposed in the recent literature may serve to promote research into neglected infectious diseases. A combination of push programmes that subsidise research inputs through direct funding and pull programmes that reward research output rather than research input may be the appropriate strategy to stimulate research into neglected diseases. On the one hand, early-stage (basic) research should be supported through push mechanisms, such as research grants or publicly financed research institutions. On the other hand, pull mechanisms, such as prize funds that link reward payments to the health impacts of effective medicines, have the potential to stimulate research into neglected diseases.
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30
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Metzger ML, Billett A, Link MP. The impact of drug shortages on children with cancer--the example of mechlorethamine. N Engl J Med 2012; 367:2461-3. [PMID: 23268661 DOI: 10.1056/nejmp1212468] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Monika L Metzger
- St. Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis, USA
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31
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Perko R, Harreld JH, Helton KJ, Sabin ND, Haidar CE, Wright KD. What goes around comes around? Wernicke encephalopathy and the nationwide shortage of intravenous multivitamins revisited. J Clin Oncol 2012; 30:e318-20. [PMID: 23008290 DOI: 10.1200/jco.2012.42.7237] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Ross Perko
- St Jude Children's Research Hospital, Memphis, TN 38105, USA
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