- Email: [email protected]
The Goldilocks' problem of cancer medicines
Reflection and Reaction
mortality from the use of 3 years’ therapy as compared with only 6 months of treatment—which has also been shown to provide a survival benefit when compared with no use of hormone therapy.3 Pending additional study, whether older men in whom testosterone rebound can be prolonged (eg, average of 16 months after 6 months of hormonal therapy in men aged 65 years and older3) require 3 years of hormonal therapy and its added toxicity as compared with 6 months’ therapy to obtain a survival benefit remains unclear. Moreover, the survival benefit of hormonal therapy might be lost in men with underlying congestive heart failure or myocardial infarction induced by coronary artery disease. Therefore, 3 years of hormonal therapy might be necessary to improve survival only for younger (age <65 years) and healthier men without coronary artery disease.
Brigham and Women’s Hospital, Dana Farber Cancer Institute, Department of Radiation Oncology, Boston, MA, USA [email protected] The author declared no conflicts of interest. 1
2
3
4
5
6
Bolla M, Gonzalez D, Warde P, et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 1997; 337: 295–300. Bolla M, Van Tienhoven G, Warde P, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol 2010; published online Oct 7. DOI:10.1016/S14702045(10)70223-0. D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Interval to testosterone recovery after hormonal therapy for prostate cancer and risk of death. Int J Radiat Oncol Biol Phys 2009; 75: 10–15. Nanda A, Chen MH, Braccioforte MH, Moran BJ, D’Amico AV. Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction. JAMA 2009; 302: 866–73. Bolla M, Collette L, Blank L, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 2002; 360: 103–08. Bolla M, de Reijke TM, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 2009; 360: 2516–27.
Anthony V D’Amico
Rarely does a week go past without a further addition to the already monumental corpus of literature on pharmaceutical policy. Cancer medicines and particularly NICE-related issues in policies and access to cancer drugs have now become the major news item for the UK media,1 adding fuel to an already flammable mixture of pharmaceutical industry and politics. In the heat of these ongoing debates, however, serious policy issues of cancer drug access, affordability, and usage remain ever present. The most recent addition to this policy debate has attempted to look into the extent and causes of international variations in drug usage in 14 countries with 14 different categories of drugs.2 This complex study used data supplied by a consulting company, IMS Health, and the manufacturers themselves. Data for drug usage were delivered as a country ranking or as a percentage of a European average made up of different combinations of countries, or as both. Overall, the UK ranked twelfth, but this method of ranking drug usage hid major variation. For example, for cancer drugs launched between 6 and 10 years ago, the UK was ranked ninth in usage but, for some individual drugs such as alemtuzumab, we were ranked first. So what are we to make of these results? The first issue, freely admitted in the report, is one of methodology. IMS www.thelancet.com/oncology Vol 11 November 2010
data has the perennial problem of being unable to directly follow through from supplier to patient, because of issues such as parallel exports and different country-specific supply chains. Furthermore, no manufacturer will allow individual country data of drug usage to be directly reported because of commercial confidentiality. Moreover, the ad-hoc expert opinions behind the various hypotheses used to explain the causes of international variations, although comprehensive, have no linkage with the data presented. Thus, we are none the wiser as to the underlying causes of these variations. The other major issue that arises from this report is whether it can tell us anything about the level of medical care for patients with cancer. Coincidentally, at the same time as this report, the New England Journal of Medicine published a study of the geographical variation in Medicare drug spending.3 This study reported a very weak correlation between the level of medical spending and that of drug spending—a finding consistent with drugs being a substitute for medical care for some patients, and a complement to medical care for others. As the authors of the New England Journal of Medicine paper note, pharmaceutical spending is variable in its own right and is not strongly associated with variations in medical spending. The IMS report therefore begs the question:
Victor Habbick Visions/Science Photo Library
The Goldilocks’ problem of cancer medicines
Published Online October 7, 2010 DOI:10.1016/S14702045(10)70224-2 See Editorial Lancet 2010; 376: 389
1017
Reflection and Reaction
are patients receiving too much, too little, or just about the right amount of cancer drugs?—the Goldilocks’ problem. Unfortunately, we are still none the wiser; with such a strong emphasis in NHS policy on patient-centred outcomes, it is a sad indictment of current research that we still cannot leverage the detailed information needed to address this question. In light of the Karolinska and subsequent imbroglio that followed report,4 the attempt to link survival with drug prescribing, opening up the necessary data to analysis would seem to be in everyone’s interest.5 It is also worth pausing for a moment to be reminded that other methods of treatment—such as surgery and radiotherapy—provide a far greater contribution to treatment and survival in solid cancers which far outweighs the contribution made by drug treatment.6 Furthermore, better physical and mental health could also contribute to better outcomes and merits further study. Assessment of cancer drug usage and the reasons for the existing variations is important, but equally, the same focus by policy makers
on the aforementioned areas would provide a far better contribution to patient outcome and wellbeing.
Richard Sullivan*, Arnie D Purushotham Kings Health Partners Integrated Cancer Centre, IEO-ICC Centre for OncoPolicy, Section of Research Oncology, Bermondsey Wing, Guy’s Hospital, Great Maze Pond, London SE1 9RT, UK. [email protected] RS has received honorarium for lectures from Pfizer and Celgene. 1
2
3 4 5
6
Lewison G, Tootell S, Roe P, Sullivan R. How do the media report cancer research? A study of the UK’s BBC website. Br J Cancer 2008; 99: 569–76. Richards MA. Extent and causes of international variations in drug usage: a report for the Secretary of State by Sir Mike Richards CBE. London: COI, 2010. http://www.dh.gov.uk/en/Publicationsandstatistics/ Publications/PublicationsPolicyAndGuidance/DH_117962 (accessed Sept 14, 2010) Zhang Y, Baicker K, Newhouse JP. Geographic variation in Medicare drug spending. N Engl J Med 2010; 363: 405–09. Coleman M. New drugs and survival: does the Karolinska report make sense? Cancer World 2006; 26–35. Coleman M. Not credible: a subversion of science by the pharmaceutical industry. Commentary on a global comparison regarding patient access to cancer drugs. Ann Oncol 2007; 18: 1433–35. Morgan G, Ward R, Barton M. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clin Oncol (R Coll Radiol) 2004; 16: 549–60.
The World Cancer Declaration: is the world catching up?
Published Online September 20, 2010 DOI:10.1016/S14702045(10)70228-X
For more on the World Cancer Declaration see Lancet Oncol 2008; 9: 810–11 For the NCD Alliance advocacy website see http:// www.NCDAlliance.org
1018
In 2008, at the Union for International Cancer Control (UICC) World Cancer Congress, cancer leaders approved and issued the World Cancer Declaration,1 demonstrating their desire to see cancer eliminated as a life-threatening disease for future generations. The declaration presented 11 targets which, if achieved by 2020, would establish momentum towards their longer term ambition. The declaration calls on leaders around the world to develop and implement national cancer control plans, to build and use population-based cancer registries, to implement policies to reduce the burden of cancer risk factors and prevent those cancers that can be prevented, to enhance screening and early detection capabilities, improve access to diagnosis and treatment, improve training and support for cancer health workers, and to ensure that palliative care and pain relief is made available to all patients in need, but especially in the last days of life. There are now 386 member organisations of UICC in over 100 countries and this number is expected to double in the next 18 months. Independent of governments, the growing number of UICC member organisations—eg, the American Cancer Society and the Lance Armstrong Foundation—has demonstrated that
there are effective solutions to address cancer issues and deliver elements of the declaration. For example, World Cancer Day, which took place on Feb 4, 2010, united UICC members in raising the profile of the link between infections and cancer. More than 2·4 billion people were exposed to the key message of the campaign—that cancer can be prevented too—and members in individual countries ran their own events to ensure the day was recognised and publicised by their local media. UICC has recently become more active in advocating its ambitions in the political sphere. In early 2009, UICC joined forces with the International Diabetes Federation and the World Heart Federation to form the Non-Communicable Disease (NCD) Alliance. This unique, common interest Alliance was established as an advocacy group to raise political awareness of the worldwide socioeconomic and health impact of NCDs, which account for 35 million (60%) of deaths in the world each year, 9 million of which can be considered premature and therefore avoidable deaths.2 In February this year, the International Union Against Tuberculosis and Lung Disease joined the Alliance, bringing the total number of organisations represented by the NCD www.thelancet.com/oncology Vol 11 November 2010
mortality from the use of 3 years’ therapy as compared with only 6 months of treatment—which has also been shown to provide a survival benefit when compared with no use of hormone therapy.3 Pending additional study, whether older men in whom testosterone rebound can be prolonged (eg, average of 16 months after 6 months of hormonal therapy in men aged 65 years and older3) require 3 years of hormonal therapy and its added toxicity as compared with 6 months’ therapy to obtain a survival benefit remains unclear. Moreover, the survival benefit of hormonal therapy might be lost in men with underlying congestive heart failure or myocardial infarction induced by coronary artery disease. Therefore, 3 years of hormonal therapy might be necessary to improve survival only for younger (age <65 years) and healthier men without coronary artery disease.
Brigham and Women’s Hospital, Dana Farber Cancer Institute, Department of Radiation Oncology, Boston, MA, USA [email protected] The author declared no conflicts of interest. 1
2
3
4
5
6
Bolla M, Gonzalez D, Warde P, et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 1997; 337: 295–300. Bolla M, Van Tienhoven G, Warde P, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol 2010; published online Oct 7. DOI:10.1016/S14702045(10)70223-0. D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Interval to testosterone recovery after hormonal therapy for prostate cancer and risk of death. Int J Radiat Oncol Biol Phys 2009; 75: 10–15. Nanda A, Chen MH, Braccioforte MH, Moran BJ, D’Amico AV. Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction. JAMA 2009; 302: 866–73. Bolla M, Collette L, Blank L, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 2002; 360: 103–08. Bolla M, de Reijke TM, Van Tienhoven G, et al. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 2009; 360: 2516–27.
Anthony V D’Amico
Rarely does a week go past without a further addition to the already monumental corpus of literature on pharmaceutical policy. Cancer medicines and particularly NICE-related issues in policies and access to cancer drugs have now become the major news item for the UK media,1 adding fuel to an already flammable mixture of pharmaceutical industry and politics. In the heat of these ongoing debates, however, serious policy issues of cancer drug access, affordability, and usage remain ever present. The most recent addition to this policy debate has attempted to look into the extent and causes of international variations in drug usage in 14 countries with 14 different categories of drugs.2 This complex study used data supplied by a consulting company, IMS Health, and the manufacturers themselves. Data for drug usage were delivered as a country ranking or as a percentage of a European average made up of different combinations of countries, or as both. Overall, the UK ranked twelfth, but this method of ranking drug usage hid major variation. For example, for cancer drugs launched between 6 and 10 years ago, the UK was ranked ninth in usage but, for some individual drugs such as alemtuzumab, we were ranked first. So what are we to make of these results? The first issue, freely admitted in the report, is one of methodology. IMS www.thelancet.com/oncology Vol 11 November 2010
data has the perennial problem of being unable to directly follow through from supplier to patient, because of issues such as parallel exports and different country-specific supply chains. Furthermore, no manufacturer will allow individual country data of drug usage to be directly reported because of commercial confidentiality. Moreover, the ad-hoc expert opinions behind the various hypotheses used to explain the causes of international variations, although comprehensive, have no linkage with the data presented. Thus, we are none the wiser as to the underlying causes of these variations. The other major issue that arises from this report is whether it can tell us anything about the level of medical care for patients with cancer. Coincidentally, at the same time as this report, the New England Journal of Medicine published a study of the geographical variation in Medicare drug spending.3 This study reported a very weak correlation between the level of medical spending and that of drug spending—a finding consistent with drugs being a substitute for medical care for some patients, and a complement to medical care for others. As the authors of the New England Journal of Medicine paper note, pharmaceutical spending is variable in its own right and is not strongly associated with variations in medical spending. The IMS report therefore begs the question:
Victor Habbick Visions/Science Photo Library
The Goldilocks’ problem of cancer medicines
Published Online October 7, 2010 DOI:10.1016/S14702045(10)70224-2 See Editorial Lancet 2010; 376: 389
1017
Reflection and Reaction
are patients receiving too much, too little, or just about the right amount of cancer drugs?—the Goldilocks’ problem. Unfortunately, we are still none the wiser; with such a strong emphasis in NHS policy on patient-centred outcomes, it is a sad indictment of current research that we still cannot leverage the detailed information needed to address this question. In light of the Karolinska and subsequent imbroglio that followed report,4 the attempt to link survival with drug prescribing, opening up the necessary data to analysis would seem to be in everyone’s interest.5 It is also worth pausing for a moment to be reminded that other methods of treatment—such as surgery and radiotherapy—provide a far greater contribution to treatment and survival in solid cancers which far outweighs the contribution made by drug treatment.6 Furthermore, better physical and mental health could also contribute to better outcomes and merits further study. Assessment of cancer drug usage and the reasons for the existing variations is important, but equally, the same focus by policy makers
on the aforementioned areas would provide a far better contribution to patient outcome and wellbeing.
Richard Sullivan*, Arnie D Purushotham Kings Health Partners Integrated Cancer Centre, IEO-ICC Centre for OncoPolicy, Section of Research Oncology, Bermondsey Wing, Guy’s Hospital, Great Maze Pond, London SE1 9RT, UK. [email protected] RS has received honorarium for lectures from Pfizer and Celgene. 1
2
3 4 5
6
Lewison G, Tootell S, Roe P, Sullivan R. How do the media report cancer research? A study of the UK’s BBC website. Br J Cancer 2008; 99: 569–76. Richards MA. Extent and causes of international variations in drug usage: a report for the Secretary of State by Sir Mike Richards CBE. London: COI, 2010. http://www.dh.gov.uk/en/Publicationsandstatistics/ Publications/PublicationsPolicyAndGuidance/DH_117962 (accessed Sept 14, 2010) Zhang Y, Baicker K, Newhouse JP. Geographic variation in Medicare drug spending. N Engl J Med 2010; 363: 405–09. Coleman M. New drugs and survival: does the Karolinska report make sense? Cancer World 2006; 26–35. Coleman M. Not credible: a subversion of science by the pharmaceutical industry. Commentary on a global comparison regarding patient access to cancer drugs. Ann Oncol 2007; 18: 1433–35. Morgan G, Ward R, Barton M. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clin Oncol (R Coll Radiol) 2004; 16: 549–60.
The World Cancer Declaration: is the world catching up?
Published Online September 20, 2010 DOI:10.1016/S14702045(10)70228-X
For more on the World Cancer Declaration see Lancet Oncol 2008; 9: 810–11 For the NCD Alliance advocacy website see http:// www.NCDAlliance.org
1018
In 2008, at the Union for International Cancer Control (UICC) World Cancer Congress, cancer leaders approved and issued the World Cancer Declaration,1 demonstrating their desire to see cancer eliminated as a life-threatening disease for future generations. The declaration presented 11 targets which, if achieved by 2020, would establish momentum towards their longer term ambition. The declaration calls on leaders around the world to develop and implement national cancer control plans, to build and use population-based cancer registries, to implement policies to reduce the burden of cancer risk factors and prevent those cancers that can be prevented, to enhance screening and early detection capabilities, improve access to diagnosis and treatment, improve training and support for cancer health workers, and to ensure that palliative care and pain relief is made available to all patients in need, but especially in the last days of life. There are now 386 member organisations of UICC in over 100 countries and this number is expected to double in the next 18 months. Independent of governments, the growing number of UICC member organisations—eg, the American Cancer Society and the Lance Armstrong Foundation—has demonstrated that
there are effective solutions to address cancer issues and deliver elements of the declaration. For example, World Cancer Day, which took place on Feb 4, 2010, united UICC members in raising the profile of the link between infections and cancer. More than 2·4 billion people were exposed to the key message of the campaign—that cancer can be prevented too—and members in individual countries ran their own events to ensure the day was recognised and publicised by their local media. UICC has recently become more active in advocating its ambitions in the political sphere. In early 2009, UICC joined forces with the International Diabetes Federation and the World Heart Federation to form the Non-Communicable Disease (NCD) Alliance. This unique, common interest Alliance was established as an advocacy group to raise political awareness of the worldwide socioeconomic and health impact of NCDs, which account for 35 million (60%) of deaths in the world each year, 9 million of which can be considered premature and therefore avoidable deaths.2 In February this year, the International Union Against Tuberculosis and Lung Disease joined the Alliance, bringing the total number of organisations represented by the NCD www.thelancet.com/oncology Vol 11 November 2010