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Global Comparator Report on Funding and Access to Oncology Drugs with special reference to South Africa Dr Nils Wilking Karolinska Institutet, Stockholm, Sweden October 6, 2007. The 2007 report An up-date and extension of the 2005 European report • A global comparison regarding patient access to cancer drugs B. Jönsson1 & N. Wilking2 1Stockholm School of Economics; 2Karolinska Institute, Stockholm, Sweden Annals of Oncology 18 (Supplement 3) 2007 • The report looked at access in 25 countries: – 19 countries in Europe – United States, Canada, Japan, Australia, New Zealand and South Africa – Total population 984 million • The European countries included in the study constitute 76% of the European population (447 million) • Data on South Africa from a sub-report in manuscript. Key points • Incidence is increasing while mortality is constant or declining • Progress in medical treatments has meant that cancer is becoming a chronic condition, incurable but treatable. However, these benefits are only realised once the drugs get to the patients. • There are great inequities between countries in the uptake and use of these drugs. South Africa. Cancer numbers. 1997-1999 Most common Cancers • cervical cancer • Breast cancer • Prostate cancer • Lung cancer • Oesophageal cancer • Kaposis sarcoma Incidence • 15-9/100 000 Mortality • 8-9/100 000 Incidence of cancer in females in selected countries (Canada, Czech Republic, Denmark, Finland, New Zealand, Norway and Sweden) given as age-standardized rate per 100.000 inhabitants. Disease All sites but non-melanoma skin Sex Female age [0-85+] Incidence 400 Age Standardised Rate (World) 350 300 Country Canada 250 Czech republic Denmark Finland 200 New Zealand Norway Sweden 150 100 50 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 0 Year Incidence of cancer in males in selected countries (Canada, Czech Republic, Denmark, Finland, New Zealand, Norway and Sweden) given as age-standardized rate per 100.000 inhabitants. Disease All sites but non-melanoma skin Sex Male age [0-85+] Incidence 400 Age Standardised Rate (World) 350 300 Country Canada 250 Czech republic Denmark Finland 200 New Zealand Norway Sweden 150 100 50 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 0 Year Mortality of cancer in females in Norway, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom and the United States of America given as age-standardized rate. Disease All cancers Sex Female age [0-85+] Mortality 300 Age Standardised Rate (World) 250 Country 200 Norway Poland Portugal Spain Sweden 150 Switzerland United Kingdom United States of America 100 50 1950 1951 1952 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 0 Year Mortality of cancer in males in Norway, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom and the United States of America given as age-standardized rate. Disease All cancers Sex Male age [0-85+] Mortality 300 Age Standardised Rate (World) 250 Country 200 Norway Poland Portugal Spain Sweden 150 Switzerland United Kingdom United States of America 100 50 1950 1951 1952 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 0 Year Incidence of breast cancer in Canada, Czech Republic, Denmark, Finland, New Zealand, Norway and Sweden given as agestandardized rate. Disease Breast Sex (Alla) Incidence 100 Age Standardised Rate (World) 90 80 70 Country Canada 60 Czech republic Denmark 50 Finland New Zealand Norway 40 Sweden 30 20 10 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 0 Year Mortality of breast cancer in Norway, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom and the United States of America given as age-standardized rate. Disease Breast Sex (Alla) DataCategory (Alla) Mortality 35 Age Standardised Rate (World) 30 Country 25 Norway Poland 20 Portugal Spain Sweden Switzerland United Kingdom 15 United States of America 10 5 1950 1951 1952 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 0 Year Causes of Death and Disease Burden The ten disease groups with largest disease burden in South Africa, with statistics for Czech Republic/Hungary/Poland and the E-13 countries presented for comparison (2002 data) Czech Republic/ Hungary/Poland South Africa E-13 Population (million) 44.8 All disease groups Total DALY/ Total DALY/ Total DALY/ DALYs 1000 % DALYs 1000 % DALYs 1000 % 20,560,460 459.4 100 9,085,571 154.8 100.0 45,027,283 123.2 100.0 HIV/AIDS 58.7 365.4 10,421,670 232.8 50.7 8,536 0.1 0.1 154,758 0.4 0.3 Injuries 1,744,778 39.0 8.5 1,047,070 17.8 11.5 3,487,994 9.5 7.7 Mental disease 1,394,840 31.2 6.8 1,970,862 33.6 21.7 12,122,002 33.2 26.9 Cardiovascular disease 958,267 21.4 4.7 1,987,288 33.9 21.9 7,447,825 20.4 16.5 Diarrhoea 478,577 10.7 2.3 15,436 0.3 0.2 96,781 0.3 0.2 Cancer 459,145 10.3 2.2 1,483,130 25.3 16.3 7,507,887 20.5 16.7 Tuberculosis 445,863 10.0 2.2 24,812 0.4 0.3 35,504 0.1 0.1 Nutritional deficiencies 443,058 9.9 2.2 54,666 0.9 0.6 264,523 0.7 0.6 Respiratory disease 419,464 9.4 2.0 286,855 4.9 3.2 2,984,745 8.2 6.6 Cancer in developing countries The Size of the Problem The incidence of cancer is lower in countries at a lower level of economic development, but they account for more than half of global cancer and a higher fraction of patients die Estimates (Africa) Adopted from Dr Ian Magrath Actual deaths Deaths per 100,000 Tuberculosis 587,000 81 Malaria 900,000+ 124 AIDS 2,400,000 331 506,111 70 Cancer Cancer is rapidly increasing, but is neglected, compared to infectious diseases These diseases interact, increasing further the burden of disease Crude Rates by Regions Adopted from Dr Ian Magrath More affluent regions have higher actual incidence and mortality rates and lower mortality: incidence ratios ASR (World) by region: Comparison: Effect of Age Adopted from Dr Ian Magrath Adjustment of rates to a world standard population shows that incidence rates would remain lower but mortality rates would increase in low income regions as populations age The Global Pattern of Cancer; Contrasts Males INCIDENCE MORTALITY Crude ASR Crude ASR N. America 530 398 210 153 W.Europe 526 326 295 174 Middle Africa 78 142 66 121 South Central Asia 76 106 55 78 Globocan 2002 Less and More Developed Crude Incidence versus Cases Adopted from Dr Ian Magrath 3500 500 3000 400 2500 300 2000 200 1500 1000 100 0 500 0 Males Less Developed Females Males Less Developed More Developed Per 100,000 per annum Females More Developed Thousands per annum 2002 A Neglected Health Problem in Low Income Countries Adopted from Dr Ian Magrath • Cancer causes more deaths globally than AIDS, malaria and TB combined • In 2002, >50% of the 11 million estimated patients with cancer and 70% of cancer deaths were in developing countries, which have perhaps 5-10% of global resources • Developing countries will account for an ever increasing fraction of the global cancer burden • The WHA has approved a resolution (May 2005) recommending that countries develop and implement cancer control plans Cancer Registration; From CI on V Continents I-VIII Adopted from Dr Ian Magrath 4% 6% Fraction of World Population 10% 14% 47% Africa Latin America N America Asia Europe Oceania 14% 9% 5% 60% 11% 1% 19% Number of registries does not accurately reflect population coverage (e.g., African registries cover approx 7 million of the 888 million people Conclusions • Cancer services are limited and already overwhelmed in developing countries in spite of relatively low cancer burden • The cancer burden will increase markedly in the next decades (150m 2000-2020) • Building human capital is a priority, but obstacles include pool of teachers, losses of personnel to better circumstances (internal or external) • Material shortages – facilities, equipment, drugs etc. – and poorly structured health services compound the problem • Poverty, illiteracy, stigmata, traditional healers create additional obstacles to care Direct and indirect cost of cancer • Cancer accounts for about 5% of all health care expenditures in the USA • The share for cancer has been stable over the last 30 years • Cost of hospitalisation is the dominating cost item • Indirect costs in terms of lost production is more than double the direct health care costs Direct costs for cancer care in selected countries in 2004. Costs are PPP (Purchasing Power Parity) adjusted. Total in million euro, per capita in euro, and share of total health care costs(%) T Europe 56 664 125 6.4 (%) United States 62 321 212 4.7 (%) Canada Japan 5 013 19 750 157 155 6.7 (%) 9.3 (%) Cost of cancer drugs in perspective • 2-2.5 new drugs per year since 1995 • Drug costs increase by 15-20 % per year • 3.5-7 % of total drug expenditure are cancer drugs. • Cancer drugs account for a minor, but growing, part (10-15%) of total cancer care expenditure Total cancer drug sales 25000000 20000000 2003-2004 15000000 2000-2002 1995-1999 <1995 10000000 5000000 0 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 Total cancer drug sales (€000s) in all 25 countries. 1995-2005 by year of first world wide launch. Source IMS Health, IMS MIDAS Quantum Limitations in Resources: Anti-Cancer Drugs Anti-Cancer Drug Sales Cancer 16% 61% 5% 18% 5% 19% 18% 61% USA Europe Japan Rest of World Approval of cancer drugs No of molecules approved 1995-2005 Average years from first launch of drug (worldwide) to sale on country market in the specific country Including drugs with sale before Q2 2006 only South Africa Czech Republic Hungary Poland United Kingdom E-13 countries 15 19 20 24 23 23 2.1 2.1 2.3 2.4 1.0 1.4 *Drugs without sale before Q2 2006 were assumed to have sale in this quarter in the calculation of time lag Including all drugs* 6.3 3.0 3.4 3.2 1.8 2.1 Limitations in Resources for Radiotherapy Adopted from Dr Ian Magrath • In Dec 2004, there were approximately 2500 radiotherapy centers and 3700 machines for cancer therapy in the developing world (enough for 1.85 million patients per year compared to 3 million who need it. • Maldistribution worsens the situation: many countries have one machine for millions of patients (1 per 250,000 in high income countries). Over 20 countries – mostly African - have none (IAEA). • Many existing machines are idle for lack of maintenance, expired sources or lack of radiotherapists or physicists • Old cobalt sources require longer radiation times Inequities between countries in the uptake and use of these drugs South Africa Cze ch Re public/Hungary/Poland 45000 450000 40000 400000 35000 350000 30000 300000 25000 250000 20000 200000 15000 150000 10000 100000 5000 50000 0 0 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 1995 1996 1997 1998 1999 Unite d Kingdom 2000 2001 2002 2003 2004 2005 E-13 900000 8000000 2003-2004 800000 2000-2002 7000000 1995-1999 700000 <1995 6000000 600000 5000000 500000 4000000 400000 3000000 300000 2000000 200000 1000000 100000 0 0 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 0 All countries SA Insured pop. South Africa Poland New Zealand Czech Republic United Kingdom Hungary Australia Norway Canada Netherlands Denmark Italy Spain Sweden Germany Finland Belgium Austria Switzerland Japan France United States PPP-adjusted per capita cancer drug sales (€) in 22 of the study countries in 2005. Distributed on drugs of different “vintage” 40 35 30 25 2003-2004 20 2000-2002 1995-1999 15 <1995 10 5 PPP-adjusted per capita cancer drug sales (€) in 2005 (For South Africa sales per capita is presented also with two capita rates for the total population as well as for the insured part (18.5%) of the population 25 20 2003-2004 15 2000-2002 1995-1999 <1995 10 5 0 South Africa SA Insured pop. Poland United Kingdom Czech Republic Hungary E-13 Gemcitabine uptake in Czech Republic, E13, Hungary, Poland, South Africa insured pop., South Africa total pop. and the UK Molecule GEMCITABINE Sales 25 000 Sum EUR per Population (100 000) 20 000 Country Czech republic 15 000 E13 Hungary Poland South Africa Ins. South Africa Tot. United Kingdom 10 000 5 000 Y01 Q1 Y01 Q2 Y01 Q3 Y01 Q4 Y02 Q1 Y02 Q2 Y02 Q3 Y02 Q4 Y03 Q1 Y03 Q2 Y03 Q3 Y03 Q4 Y04 Q1 Y04 Q2 Y04 Q3 Y04 Q4 Y05 Q1 Y05 Q2 Y05 Q3 Y05 Q4 Y06 Q1 Y06 Q2 Y06 Q3 Y06 Q4 Y07 Q1 Y07 Q2 Y07 Q3 Y07 Q4 Y08 Q1 Y08 Q2 Y08 Q3 Y08 Q4 Y09 Q1 Y09 Q2 Y09 Q3 Y09 Q4 Y10 Q1 Y10 Q2 Y10 Q3 Y10 Q4 Y11 Q1 Y11 Q2 Y11 Q3 0 YearQuarter Imatinib uptake in Czech Republic, E13, Hungary, Poland, South Africa insured pop., South Africa total pop. and the UK Molecule IMATINIB Sales 60 000 Sum EUR per Population (100 000) 50 000 Country 40 000 Czech republic E13 Hungary Poland 30 000 South Africa Ins. South Africa Tot. 20 000 United Kingdom 10 000 0 Y01 Q1 Y01 Q2 Y01 Q3 Y01 Q4 Y02 Q1 Y02 Q2 Y02 Q3 Y02 Q4 Y03 Q1 Y03 Q2 Y03 Q3 YearQuarter Y03 Q4 Y04 Q1 Y04 Q2 Y04 Q3 Y04 Q4 Y05 Q1 Y05 Q2 Y05 Q3 Rituximab uptake in Czech Republic, E13, Hungary, Poland, South Africa insured pop., South Africa total pop. and the UK Molecule RITUXIMAB Sales 40 000 Sum EUR per Population (100 000) 35 000 30 000 Country Czech republic 25 000 E13 Hungary Poland 20 000 South Africa Ins. South Africa Tot. United Kingdom 15 000 10 000 5 000 YearQuarter Y09 Q1 Y08 Q4 Y08 Q3 Y08 Q2 Y08 Q1 Y07 Q4 Y07 Q3 Y07 Q2 Y07 Q1 Y06 Q4 Y06 Q3 Y06 Q2 Y06 Q1 Y05 Q4 Y05 Q3 Y05 Q2 Y05 Q1 Y04 Q4 Y04 Q3 Y04 Q2 Y04 Q1 Y03 Q4 Y03 Q3 Y03 Q2 Y03 Q1 Y02 Q4 Y02 Q3 Y02 Q2 Y02 Q1 Y01 Q4 Y01 Q3 Y01 Q2 Y01 Q1 0 Trastuzumab uptake in Czech Republic, E13, Hungary, Poland, South Africa insured pop., South Africa total pop. and the UK Molecule TRASTUZUMAB Sales 40 000 Sum EUR per Population (100 000) 35 000 30 000 Country Czech republic 25 000 E13 Hungary Poland 20 000 South Africa Ins. South Africa Tot. 15 000 United Kingdom 10 000 5 000 0 Y01 Y01 Y01 Y01 Y02 Y02 Y02 Y02 Y03 Y03 Y03 Y03 Y04 Y04 Y04 Y04 Y05 Y05 Y05 Y05 Y06 Y06 Y06 Y06 Y07 Y07 Y07 Y07 Y08 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 YearQuarter In many countries new drugs are not reaching patients quickly enough • Austria, France, Switzerland and the US are the leaders in the use of new cancer drugs, with France replacing Spain among the top four since the 2005 report was published. • Uptake of new cancer drugs is “low and slow” in New Zealand, Poland, Czech Republic, South Africa and the UK. Questions to be sorted out • Is improved cancer survival related to access to cancer drugs? – or to early detection; change in biology and diagnosis; surgery and radiation therapy? • Does survival improvement in clinical trials translate into survival effects in a population with cancer? – If yes: How do we measure this? – If no: “Then we have a real problem…” Contribution of the increase in cancer drug vintage to the decline in the age-adjusted cancer mortality rate. Frank Lichtenberg; Columbia University, NY,NY. 1.05 actual 1.00 if no increase in drug vintage 0.95 0.90 0.89 0.85 0.84 0.80 1995 1996 1997 1998 1999 2000 2001 2002 2003 Increase in drug vintage accounts for 30% of the 1995-2003 decline in the age-adjusted cancer mortality rate. Actions proposed • Give us better data!! – Move from 10 year old epidemiology data to real time data on ”Impact of Preventive, Diagnostic and Therapeutic Interventions” (iPDTi) • Common medical view on risks and benefits • Post marketing studies – CRT or non-interventional trials • Special budget for innovative treatments • Take a global perspective – • Cancer in the developing countries will be a major challenge. Re-think price and volume Final comments • Patients should have equal and early access to innovative treatments • Research on access of therapy is an important part of cancer research