- Email: [email protected]
Access to essential medicines for children with cancer: a joint SIOP-CCI position statement
Comment
control the cancer burden. In Nigeria, about 102 000 new cases of cancer occur annually, and 75 000 deaths per year are caused by cancer.3 One key area in which the new agency can contribute to reducing cancer mortality in Nigeria is improving access to cancer medicines. In Nigeria, cancer is not covered under the national health insurance scheme and the cost of cancer medicines is prohibitive.2 For instance, a course of trastuzumab for patients with breast cancer costs more than US$1585,2 which is about 28-times the monthly wage of the lowest-paid government worker in Nigeria. Given that the challenge of access to cancer medications in low-income and middle-income countries such as Nigeria can only be effectively tackled through a combination of public and private efforts,4 the new agency would be in a position to coordinate and mobilise partnerships for funding and technical support for access to cancer medicines in Nigeria, similar to what has been achieved by the National Agency for the Control of AIDS, who has gained leverage over multistakeholder public–private partnerships to provide free or heavily subsided HIV medicines to Nigerian patients. Certainly, the model of national and international public–private partnerships deployed in the
improvement of financing and delivery of HIV medicines in low-income and middle-income countries is possible with cancer treatments.5 Therefore, the Nigerian Government is urged to expedite actions towards the take-off of the proposed agency and to engage with all relevant stakeholders from both the public and private sectors in its planning and operation to ensure effective and sustainable delivery of cancer care in Nigeria. Omotayo Fatokun Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, UCSI University, Cheras 56000, Kuala Lumpur, Malaysia [email protected] I declare no competing interests. 1
2
3 4 5
Federal Ministry of Health (Nigeria). FG to establish national agency for cancer control. http://www.health.gov.ng/index.php/news-media/pressreleases/9-uncategorised/286-fg-to-establish-national-agency-for-cancercontrol (accessed Nov 7, 2016). Chidebe RC. Cancer control agency and the burden of the disease in Nigeria. The Authority (Nigeria), Oct 20, 2016. http://www.authorityngr. com/2016/10/Cancer-%20Control-agency-and-the-burden-of-thedisease-in-Nigeria (accessed Nov 17, 2016). Stefan DC, Elzawawy AM, Khaled HM, et al. Developing cancer control plans in Africa: examples from five countries. Lancet Oncol 2013; 14: e189–95. Lopes GL, de Souza JA, Barrios C. Access to cancer medications in low- and middle-income countries. Nat Rev Clin Oncol 2013; 10: 314–22. Farmer P, Frenk J, Knaul FM, et al. Expansion of cancer care and control in countries of low and middle income: a call to action. Lancet 2010; 376: 1186–93.
Access to essential medicines for children with cancer: a joint SIOP-CCI position statement Treatment of cancer in childhood is both a major success of modern medicine and a stark reminder of its limits. In high-income countries, multimodality therapy cures more than 80% of children.1 In low-income and middle-income countries (LMICs), where most children with cancer live, far fewer children are cured than in high-income countries. Access to essential medicines is one of the key determinants of cancer survival globally. WHO’s Essential Medicines List (EML) sets the basic bar that all national governments should meet in provision of medicines.2 The revised EML includes an expanded list of core medicines required for multiple malignancies, including the most prevalent paediatric cancers.3 Ensuring access to such medicines is an explicit component of the broad right to health enshrined in international human rights conventions.4 20
The International Society of Paediatric Oncology (SIOP) and Childhood Cancer International (CCI) held a symposium at the 48th SIOP Congress in Dublin, Ireland, on Oct 19, 2016, entitled “Essential medicines for children with cancer: dynamics and challenges”. Major challenges and potential solutions related to access to these medicines in LMICs were explored, and priority actions to improve global access were identified. Access to medicines is a complex issue, involving components from drug development to delivery. This joint position statement summarises the symposium’s key consensus findings to galvanise the international oncology community to achieve sustained improvements in access to medicines for children with cancer, regardless of disease or geography. The deliberations, situational analysis, and recommendations were framed by four www.thelancet.com/oncology Vol 18 January 2017
Comment
commonly cited core domains of access: availability, accessibility, acceptability, and affordability; we included quality as a fifth domain.5 Availability relates to how medicines are produced and distributed. Barriers to availability include but are not limited to: inadequate drug production, secondary to weak market incentives or poor forecasting of childhood cancer treatment needs; national failures to comply with EML recommendations; and rigid regulatory frameworks governing drug licensing and importation. Accessibility refers to a given medicine’s location in relation to the person in need. Cancer medicines are often inaccessible in LMICs because of weak systems of supply management, including poor inventory controls, fractured supply channels, and inadequate infrastructure for proper transport and storage. These complexities are exacerbated by socioeconomic and geographical factors in many LMICs, principally the effects of poverty and rurality on patients’ abilities to reach needed medicines. Acceptability considers the design characteristics of existing medicines and how these align with patient and provider expectations and experiences. Medicines for children with cancer are distinct since many require formulation as sterile injectables; consequently, they are complicated to produce, require cold storage, and have short shelf lives. Moreover, they are dosed by weight or body surface area, making it difficult to manufacture vials that minimise waste, or for pills, doses appropriate to varying stages of child development. These characteristics often limit drug acceptability to provider and patient alike, particularly in LMICs. Affordability refers to the relationships between cost, price, and ability to pay and addresses issues related to drug price determination, how medicines are purchased, and the effects of these factors on patient access. Despite the fact that most cytotoxic agents for children are available in generic formulation, cost-related barriers persist. These barriers rest on multiple factors, including national resource constraints and competing health system priorities; small, fragmented markets for paediatric cancer drugs; thin industry profit margins due to patent expiry; and absence of public or employerbased health insurance. Quality incorporates appraisals of drug safety and efficacy and addresses problems related to drug www.thelancet.com/oncology Vol 18 January 2017
Panel: Recommendations to improve global access to childhood cancer medicines Availability • Development of a database listing reliable suppliers of essential medicines for children with cancer • Research to assess and understand barriers to national formulary compliance with EML recommendations across LMICs • WHO-led attempts to harmonise national regulatory regimes through regional collaboration to facilitate pooled procurement • Efforts to develop a not-for-profit capacity for development of off-patent cytotoxic drugs for children, with the potential for global scale-up Accessibility • Human resource investments in paediatric pharmacists, whose scientific and on-theground knowledge is crucial to sound policies on supply chain management for antineoplastic drugs • Development of specific guidelines on infrastructural and oversight requirements for injectable chemotherapeutics for children • Formalised voice for childhood cancer experts in national policy making on drug procurement and supply Acceptability • Development of intrainstitutional and interinstitutional policies to minimise waste of medicines • Regional partnerships with trusted producers to ensure reliable production processes, with a view to minimisation of introduction of potential harmful excipients • Research into patient and provider experiences of use of cancer medicines in LMIC settings Affordability • Expanded public insurance coverage for essential childhood cancer medicines for children with cancer • Regionally pooled purchasing • Reduction or removal of importation tariffs on childhood cancer medicines • Exploration of innovative financing approaches to provision of off-patent cytotoxic drugs Quality • Development of a WHO-certified list of reputable drug suppliers and formulations to guide national procurement • Improved methods of interinstitutional and health-care user knowledge sharing on drug quality, including through creative uses of mobile technology, to facilitate improved postmarketing quality surveillance • Enhanced training programs for LMIC pharmacists and bedside providers in safe and accurate preparation and administration of chemotherapeutics in children • Expanded research into new, cost-effective, point-of-care quality diagnostics EML=Essential Medicines List. LMIC=low-income and middle-income country.
provenance, including counterfeiting, improper production, and inadequate quality surveillance. The capacity for generic production of most essential medicines for children with cancer is a double-edged sword: it lowers prices but diffuses production, complicating assessments of drug origination and thus quality assurances. Such assurances are further compromised in many LMICs by weak or absent pharmacovigilance in the 21
Comment
face of decentralised and often labyrinthine systems of drug procurement and supply. Our recommendations to improve global access to childhood cancer medicines are summarised in the panel. Gathering appreciation of the mounting role that cancer will play in global childhood mortality has created a window of opportunity for political action on this issue. SIOP and CCI commit to joint engagement with key academic, policy, advocacy, and industry stakeholders to advance these recommendations. Ongoing efforts include formal collaboration with WHO on iterative updates to the EML for children and plans for cross-sectoral consultation at in-depth symposia during the 2017 SIOP and CCI Annual Congresses in Washington, DC, USA. Only sustained advocacy and effective policies in line with our recommendations will induce real and lasting gains in access to essential medicines for all children with cancer.
Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, M5G 1X8, Canada (AD); Tata Memorial Hospital, Mumbai, India (BA); Max Super Speciality Hospital, Saket, New Delhi, India (RSA); Childhood Cancer International, Manila, Philippines (CA); Childhood Cancer International, New Delhi, India (PB); Department of Pediatrics, McMaster University, Hamilton, Canada (RB); School of Nursing, University of California San Francisco, San Francisco, CA, USA (JC); World Child Cancer, London, UK (TE); Fundación Natalí Dafne Flexer, Buenos Aires, Argentina (EG); American Childhood Cancer Organization, Washington, DC, USA (RH); and Stanford University School of Medicine, Palo Alto, CA, USA (ML) [email protected] We declare no competing interests. We thank all participants in the joint International Society of Paediatric Oncology-Childhood Cancer International Essential Medicines Symposium at the 48th International Society of Paediatric Oncology Congress in Dublin, Ireland, on Oct 19, 2016, on whose insights and input this position statement is based. 1
2 3
*Avram Denburg, Brijesh Arora, Ramandeep Singh Arora, Carmen Auste, Poonam Bagai, Ronald Barr, Julia Challinor, Tim Eden, Edith Grynzspancholc, Ruth Hoffman, Michael Link
4
5
Rodriguez-Galindo C, Friedrich P, Alcasabas P, et al. Toward the cure of all children with cancer through collaborative efforts: pediatric oncology as a global challenge. J Clin Oncol 2015; 33: 3065–73. WHO. WHO model list of essential medicines: 19th list. Geneva: World Health Organization, 2015. WHO. The selection and use of essential medicines. Geneva: World Health Organization, 2015. UN. International covenant on economic, social and cultural rights. 16 Dec, 1966. http://www.ohchr.org/Documents/ProfessionalInterest/cescr.pdf (accessed Oct 20, 2016). Management Sciences for Health. Managing access to medicines and health technologies. Arlington: Management Sciences for Health, 2012.
Biosimilar and generic cancer drugs unlikely to bend cost curve in the USA
Sputnik/Science Photo Library
Although biosimilar and generic oncology drugs have been positioned as so-called cost game-changers to the worldwide drug market, this label might be premature as it is unlikely that they will bend the cancer cost curve in the USA.1,2 Generic drugs have the exact structure as their reference products, and assays indicate they typically have bioavailability between 80% and 125% of reference molecules. Oncology biosimilar products, which are close copies of biological medicines, were first approved in the USA in 2015 with the biosimilar filgrastim. The biosimilar regulatory framework is substantially different from that for generics and is rapidly evolving with substantial country-to-country variation. 10 years of filgrastim biosimilars in Europe have resulted in cost reductions of 45%–60%. 1 year with biosimilar filgrastim in the USA, on the other hand, has resulted in cost savings of only 10%;3 however, 22
in the USA there is only one biosimilar filgrastim and one reference filgrastim. Generic imatinib in the USA was associated with purchasing savings of 2%–4%;4 however, generic imatinib outside the USA has been associated with purchasing savings of 50%–95%.4,5 The price of patented imatinib in the USA is US$146 000 per year and $30 000–38 000 per year in Europe and Canada.5 The price of generic imatinib is $140 000 per year in the USA, but only $5000–8000 per year in Canada, and $400 per year in India and other developing nations.4 Why are cost savings so low in the USA for both biosimilars and generics? One reason might lie in litigation: the US Department of Justice and 18 state attorney generals have initiated lawsuits against generic manufacturers, alleging collusion in pricing. The US Food and Drug Administration (FDA) might also play a role: empirical data6 show that cost savings occur with www.thelancet.com/oncology Vol 18 January 2017
control the cancer burden. In Nigeria, about 102 000 new cases of cancer occur annually, and 75 000 deaths per year are caused by cancer.3 One key area in which the new agency can contribute to reducing cancer mortality in Nigeria is improving access to cancer medicines. In Nigeria, cancer is not covered under the national health insurance scheme and the cost of cancer medicines is prohibitive.2 For instance, a course of trastuzumab for patients with breast cancer costs more than US$1585,2 which is about 28-times the monthly wage of the lowest-paid government worker in Nigeria. Given that the challenge of access to cancer medications in low-income and middle-income countries such as Nigeria can only be effectively tackled through a combination of public and private efforts,4 the new agency would be in a position to coordinate and mobilise partnerships for funding and technical support for access to cancer medicines in Nigeria, similar to what has been achieved by the National Agency for the Control of AIDS, who has gained leverage over multistakeholder public–private partnerships to provide free or heavily subsided HIV medicines to Nigerian patients. Certainly, the model of national and international public–private partnerships deployed in the
improvement of financing and delivery of HIV medicines in low-income and middle-income countries is possible with cancer treatments.5 Therefore, the Nigerian Government is urged to expedite actions towards the take-off of the proposed agency and to engage with all relevant stakeholders from both the public and private sectors in its planning and operation to ensure effective and sustainable delivery of cancer care in Nigeria. Omotayo Fatokun Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, UCSI University, Cheras 56000, Kuala Lumpur, Malaysia [email protected] I declare no competing interests. 1
2
3 4 5
Federal Ministry of Health (Nigeria). FG to establish national agency for cancer control. http://www.health.gov.ng/index.php/news-media/pressreleases/9-uncategorised/286-fg-to-establish-national-agency-for-cancercontrol (accessed Nov 7, 2016). Chidebe RC. Cancer control agency and the burden of the disease in Nigeria. The Authority (Nigeria), Oct 20, 2016. http://www.authorityngr. com/2016/10/Cancer-%20Control-agency-and-the-burden-of-thedisease-in-Nigeria (accessed Nov 17, 2016). Stefan DC, Elzawawy AM, Khaled HM, et al. Developing cancer control plans in Africa: examples from five countries. Lancet Oncol 2013; 14: e189–95. Lopes GL, de Souza JA, Barrios C. Access to cancer medications in low- and middle-income countries. Nat Rev Clin Oncol 2013; 10: 314–22. Farmer P, Frenk J, Knaul FM, et al. Expansion of cancer care and control in countries of low and middle income: a call to action. Lancet 2010; 376: 1186–93.
Access to essential medicines for children with cancer: a joint SIOP-CCI position statement Treatment of cancer in childhood is both a major success of modern medicine and a stark reminder of its limits. In high-income countries, multimodality therapy cures more than 80% of children.1 In low-income and middle-income countries (LMICs), where most children with cancer live, far fewer children are cured than in high-income countries. Access to essential medicines is one of the key determinants of cancer survival globally. WHO’s Essential Medicines List (EML) sets the basic bar that all national governments should meet in provision of medicines.2 The revised EML includes an expanded list of core medicines required for multiple malignancies, including the most prevalent paediatric cancers.3 Ensuring access to such medicines is an explicit component of the broad right to health enshrined in international human rights conventions.4 20
The International Society of Paediatric Oncology (SIOP) and Childhood Cancer International (CCI) held a symposium at the 48th SIOP Congress in Dublin, Ireland, on Oct 19, 2016, entitled “Essential medicines for children with cancer: dynamics and challenges”. Major challenges and potential solutions related to access to these medicines in LMICs were explored, and priority actions to improve global access were identified. Access to medicines is a complex issue, involving components from drug development to delivery. This joint position statement summarises the symposium’s key consensus findings to galvanise the international oncology community to achieve sustained improvements in access to medicines for children with cancer, regardless of disease or geography. The deliberations, situational analysis, and recommendations were framed by four www.thelancet.com/oncology Vol 18 January 2017
Comment
commonly cited core domains of access: availability, accessibility, acceptability, and affordability; we included quality as a fifth domain.5 Availability relates to how medicines are produced and distributed. Barriers to availability include but are not limited to: inadequate drug production, secondary to weak market incentives or poor forecasting of childhood cancer treatment needs; national failures to comply with EML recommendations; and rigid regulatory frameworks governing drug licensing and importation. Accessibility refers to a given medicine’s location in relation to the person in need. Cancer medicines are often inaccessible in LMICs because of weak systems of supply management, including poor inventory controls, fractured supply channels, and inadequate infrastructure for proper transport and storage. These complexities are exacerbated by socioeconomic and geographical factors in many LMICs, principally the effects of poverty and rurality on patients’ abilities to reach needed medicines. Acceptability considers the design characteristics of existing medicines and how these align with patient and provider expectations and experiences. Medicines for children with cancer are distinct since many require formulation as sterile injectables; consequently, they are complicated to produce, require cold storage, and have short shelf lives. Moreover, they are dosed by weight or body surface area, making it difficult to manufacture vials that minimise waste, or for pills, doses appropriate to varying stages of child development. These characteristics often limit drug acceptability to provider and patient alike, particularly in LMICs. Affordability refers to the relationships between cost, price, and ability to pay and addresses issues related to drug price determination, how medicines are purchased, and the effects of these factors on patient access. Despite the fact that most cytotoxic agents for children are available in generic formulation, cost-related barriers persist. These barriers rest on multiple factors, including national resource constraints and competing health system priorities; small, fragmented markets for paediatric cancer drugs; thin industry profit margins due to patent expiry; and absence of public or employerbased health insurance. Quality incorporates appraisals of drug safety and efficacy and addresses problems related to drug www.thelancet.com/oncology Vol 18 January 2017
Panel: Recommendations to improve global access to childhood cancer medicines Availability • Development of a database listing reliable suppliers of essential medicines for children with cancer • Research to assess and understand barriers to national formulary compliance with EML recommendations across LMICs • WHO-led attempts to harmonise national regulatory regimes through regional collaboration to facilitate pooled procurement • Efforts to develop a not-for-profit capacity for development of off-patent cytotoxic drugs for children, with the potential for global scale-up Accessibility • Human resource investments in paediatric pharmacists, whose scientific and on-theground knowledge is crucial to sound policies on supply chain management for antineoplastic drugs • Development of specific guidelines on infrastructural and oversight requirements for injectable chemotherapeutics for children • Formalised voice for childhood cancer experts in national policy making on drug procurement and supply Acceptability • Development of intrainstitutional and interinstitutional policies to minimise waste of medicines • Regional partnerships with trusted producers to ensure reliable production processes, with a view to minimisation of introduction of potential harmful excipients • Research into patient and provider experiences of use of cancer medicines in LMIC settings Affordability • Expanded public insurance coverage for essential childhood cancer medicines for children with cancer • Regionally pooled purchasing • Reduction or removal of importation tariffs on childhood cancer medicines • Exploration of innovative financing approaches to provision of off-patent cytotoxic drugs Quality • Development of a WHO-certified list of reputable drug suppliers and formulations to guide national procurement • Improved methods of interinstitutional and health-care user knowledge sharing on drug quality, including through creative uses of mobile technology, to facilitate improved postmarketing quality surveillance • Enhanced training programs for LMIC pharmacists and bedside providers in safe and accurate preparation and administration of chemotherapeutics in children • Expanded research into new, cost-effective, point-of-care quality diagnostics EML=Essential Medicines List. LMIC=low-income and middle-income country.
provenance, including counterfeiting, improper production, and inadequate quality surveillance. The capacity for generic production of most essential medicines for children with cancer is a double-edged sword: it lowers prices but diffuses production, complicating assessments of drug origination and thus quality assurances. Such assurances are further compromised in many LMICs by weak or absent pharmacovigilance in the 21
Comment
face of decentralised and often labyrinthine systems of drug procurement and supply. Our recommendations to improve global access to childhood cancer medicines are summarised in the panel. Gathering appreciation of the mounting role that cancer will play in global childhood mortality has created a window of opportunity for political action on this issue. SIOP and CCI commit to joint engagement with key academic, policy, advocacy, and industry stakeholders to advance these recommendations. Ongoing efforts include formal collaboration with WHO on iterative updates to the EML for children and plans for cross-sectoral consultation at in-depth symposia during the 2017 SIOP and CCI Annual Congresses in Washington, DC, USA. Only sustained advocacy and effective policies in line with our recommendations will induce real and lasting gains in access to essential medicines for all children with cancer.
Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, M5G 1X8, Canada (AD); Tata Memorial Hospital, Mumbai, India (BA); Max Super Speciality Hospital, Saket, New Delhi, India (RSA); Childhood Cancer International, Manila, Philippines (CA); Childhood Cancer International, New Delhi, India (PB); Department of Pediatrics, McMaster University, Hamilton, Canada (RB); School of Nursing, University of California San Francisco, San Francisco, CA, USA (JC); World Child Cancer, London, UK (TE); Fundación Natalí Dafne Flexer, Buenos Aires, Argentina (EG); American Childhood Cancer Organization, Washington, DC, USA (RH); and Stanford University School of Medicine, Palo Alto, CA, USA (ML) [email protected] We declare no competing interests. We thank all participants in the joint International Society of Paediatric Oncology-Childhood Cancer International Essential Medicines Symposium at the 48th International Society of Paediatric Oncology Congress in Dublin, Ireland, on Oct 19, 2016, on whose insights and input this position statement is based. 1
2 3
*Avram Denburg, Brijesh Arora, Ramandeep Singh Arora, Carmen Auste, Poonam Bagai, Ronald Barr, Julia Challinor, Tim Eden, Edith Grynzspancholc, Ruth Hoffman, Michael Link
4
5
Rodriguez-Galindo C, Friedrich P, Alcasabas P, et al. Toward the cure of all children with cancer through collaborative efforts: pediatric oncology as a global challenge. J Clin Oncol 2015; 33: 3065–73. WHO. WHO model list of essential medicines: 19th list. Geneva: World Health Organization, 2015. WHO. The selection and use of essential medicines. Geneva: World Health Organization, 2015. UN. International covenant on economic, social and cultural rights. 16 Dec, 1966. http://www.ohchr.org/Documents/ProfessionalInterest/cescr.pdf (accessed Oct 20, 2016). Management Sciences for Health. Managing access to medicines and health technologies. Arlington: Management Sciences for Health, 2012.
Biosimilar and generic cancer drugs unlikely to bend cost curve in the USA
Sputnik/Science Photo Library
Although biosimilar and generic oncology drugs have been positioned as so-called cost game-changers to the worldwide drug market, this label might be premature as it is unlikely that they will bend the cancer cost curve in the USA.1,2 Generic drugs have the exact structure as their reference products, and assays indicate they typically have bioavailability between 80% and 125% of reference molecules. Oncology biosimilar products, which are close copies of biological medicines, were first approved in the USA in 2015 with the biosimilar filgrastim. The biosimilar regulatory framework is substantially different from that for generics and is rapidly evolving with substantial country-to-country variation. 10 years of filgrastim biosimilars in Europe have resulted in cost reductions of 45%–60%. 1 year with biosimilar filgrastim in the USA, on the other hand, has resulted in cost savings of only 10%;3 however, 22
in the USA there is only one biosimilar filgrastim and one reference filgrastim. Generic imatinib in the USA was associated with purchasing savings of 2%–4%;4 however, generic imatinib outside the USA has been associated with purchasing savings of 50%–95%.4,5 The price of patented imatinib in the USA is US$146 000 per year and $30 000–38 000 per year in Europe and Canada.5 The price of generic imatinib is $140 000 per year in the USA, but only $5000–8000 per year in Canada, and $400 per year in India and other developing nations.4 Why are cost savings so low in the USA for both biosimilars and generics? One reason might lie in litigation: the US Department of Justice and 18 state attorney generals have initiated lawsuits against generic manufacturers, alleging collusion in pricing. The US Food and Drug Administration (FDA) might also play a role: empirical data6 show that cost savings occur with www.thelancet.com/oncology Vol 18 January 2017