© 2007 European Society for Medical Oncology
letters to the editor |
Reply to ‘Not credible: a subversion of science by the pharmaceutical industry. Commentary on A global comparison regarding patient access to cancer drugs (Annals of Oncology 2007, vol 18, Suppl 3, pp1-75)’ by Michel P Coleman
Declaration of interest: All authors have received research grants and honoraria for lectures and advisory from the pharmaceutical industry at different occasions, including funding from Roche for the study A Global comparison regarding patient access to cancer drugs.Professor Coleman wrongly states that the key question addressed in our report is ‘whether national cancer survival is associated with national cancer drug licensing’. That explains his comments, but also reveals that he has no interest in, or contribution to, the main issues addressed: how does patients' access to cancer drugs vary between countries, what are the explanations for this variation, and what are the possible policy responses at national and international levels. In particular we are interested in the impact of health technology assessment, and the role of reimbursement and mechanisms for funding. Everyone who is interested in these issues has to read the report.
When the Karolinska report was published in 2005, Professor Coleman made sweeping criticisms of the chapter on the relation between new drug introduction and survival (5 pages out of 95) in different media. This chapter was a summary of two studies by Professor Frank Lichtenberg, Columbia University, which were of interest in the context of the report, but not its core. However, his interest and critique triggered us to address some shortcomings of those studies: mainly that they were based on availability and not actual utilization of drugs introduced at different times, which we call ‘vintage’. In the extended and updated report we therefore include three new studies with new data sets. Coleman chooses to ignore two of them, and focus on the third.
We will take Coleman's critical points on this study seriously and try to address them, even if it becomes a little technical. The method used in one of the three analyses is to examine the relationship between drug vintage and survival rates for 18 different types of cancer in France, Spain, Germany, Italy and the UK. Vintage is measured as the share of the sample treated with drugs introduced after 1985. Survival rates are estimated by dividing 1-year and 5-year prevalence with incidence. In the statistical analysis the country dummies (
i's) in Equation 2 control for overall (not site-specific) differences across countries in expected survival (background mortality). The cancer-site dummies (
j's) in Equation 2 control for average (across countries) differences across cancer sites in expected survival [1].
Since the survival rate is the dependent variable in Equation 2, random errors of measurement will not bias the drug vintage coefficient. Moreover, if survival estimates for a given country are systematically over- or under-estimated (e.g. estimates for France are overestimated by 25% for every cancer site), this will have no effect on our estimates of the effect of vintage on survival (due to inclusion of country dummies (i's) in Equation 2).
The fact that the periods studied do not completely overlap for drug usage and survival estimates is also a shortcoming, but nothing that necessary leads to systematic bias. But it may explain why the difference in post-1985 drugs accounts for only 14–19% of the observed survival difference between UK and the other countries. We are looking forward to re-estimating the model when the data from EUROCARE-4 are published later this year, and see if the results change.
The idea to use individual patient data from IMS Oncology, and include other treatments as explanatory variables may work, but it has to be investigated further. Actually, in the US survival study, the first of our studies which is ignored by Professor Coleman, we are including measures of innovation in surgery and radiology, but they do not show any systematic effect. It may be that the measures are too crude or that the effect is small. To address the problem with survival measures we also did a third study with mortality as outcome. That also has its pros and cons, but is certainly of interest since reduction in cancer mortality is a defined goal for many cancer programs.
Being aware of the data problems involved we approach the question about the relation between drug ‘vintage’ and survival in three different ways. We got consistent results so far.
The studies on the relation between innovation and survival have never been intended for use by regulatory authorities as basis for claims of effectiveness of specific drugs. They belong in a very different research tradition where the purpose is to understand the forces behind and consequences of medical research and innovation[2, 3, 4, 5]. That this field uses other data sets and research methods, developed in economics and econometrics gives no reason to label them as unscientific. They are complementary to clinical and epidemiological studies, but of course compete with such studies for policy relevance. It is understandable that Professor Coleman is irritated that economists dare to come into his field, but to call such studies ‘a subversion of science by pharmaceutical industry’ does not contribute to a serious discussion. Professor Coleman's comments indicate that he doesn't really understand the econometric methods, and is eager to use any imperfections in the data as an excuse to dismiss the results, even when those imperfections in the data are irrelevant or even render our tests of the key hypothesis ‘strong tests’.
Let us make this clear. Despite insinuations about the opposite, neither Roche nor any other pharmaceutical firm influenced the content of the report. The potential conflict of interest related to the funding from Roche has been openly declared. We have had no knowledge about anything related to Cancer United, and we have not approved their use of our report. We have not made any attempts to market the results to influence the UK health policy debate. Our study includes 29 countries, of which the UK is only one. As for other countries we make some observations. For UK we stressed in the first report particularly that HTA studies to be a useful instrument in policy have to be timely, and can also note that NICE has taken account of this. We also observed that it was nearly impossible to find any reliable estimates about cancer spending in the UK, and that this may explain the lack of correspondence between assessment and resource allocation. Our advice was to make sure that this information should be produced and made public. We can have an informed debate about priorities only if we know what we spend.
‘Prof Coleman, Harpal Kumar, the new chief executive of Cancer Research UK, and the government's cancer tsar, Mike Richards, all dismissed a report last week’ (The Guardian, 16 May 2007 after the publication in Annals). Of course the UK public can be reassured that everything is fine, guaranteed by science, the country's leading cancer funding body and the government, but does it make Professor Coleman's critique of our report credible? How independent are you in this discussion when you head ‘Cancer Research UK Survival group’?
As Professor Coleman recognizes in his conclusions, the issues we are researching are interesting and important. We have not misused, and have no intention of misusing, cancer statistics for any purposes. The problem is that current cancer statistics is inadequate to address the important issues we are studying, and the need for improvements is urgent. If Professor Coleman agrees, we are happy to collaborate on both data and methodology in any future studies.
1 Department of Economics, Stockholm School of Economics, Box 6501, SE 113 83 Stockholm, Sweden
2 University of Columbia, NY, USA
3 Karolinska Institute, Stockholm, Sweden
* E-mail: Bengt.Jonsson{at}hhs.se
References
1. Jönsson B, Wilking N. A global comparison regarding patient access to cancer drugs. Ann Oncol (2007) 18(Suppl. 3). 72.
2. Murphy KM, Topel RH. Measuring the gains from medical research. An economic approach. (2003) The University of Chicago Press.
3. Luce BR, Mauskopf J, Sloan FA, Osterman J, Paramore LC. The Return on Investment in Health Care: From 1980–2000. Value in Health (2006) 9:146–156.[CrossRef][Web of Science][Medline]
4. Buxton M. Substantial Returns to Health care Spending: But Do We Spend to Little or Too Much? Value in Health (2006) 9:144–145.[CrossRef][Web of Science][Medline]
5. Lichtenberg F. The impact of new drug launches on longevity: evidence from longitudinal disease level data from 52 countries, 1982–2001. Int J Health care Finance Econ (2005) 5:47–73.[CrossRef][Medline]
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