- Email: [email protected]
Standardised packaging and tobacco-industry-funded research
Correspondence
5
van Meerbeeck JP, Kramer GW, Van Schil PE, et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Inst 2007; 99: 442–50. Felip E, Rosell R, Maestre JA, et al, and the Spanish Lung Cancer Group. Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alonein early-stage nonsmall-cell lung cancer. J Clin Oncol 2010; 28: 3138–45.
Authors’ reply We thank Gerard Hanna and
colleagues for their interest in our study, 1 and agree it raises questions about the best sequence of treatments for patients with operable non-small-cell lung cancer. We found no difference in the number of complete resections between patients receiving chemotherapy compared with those receiving immediate surgery. Equally, although the numbers of patients are small, we found no increase in the number of incomplete resections for patients receiving chemotherapy, although this finding was not clearly reported. Unfortunately, with the data we have collected, we cannot reliably distinguish between disease progression and disease recurrence. As described in our paper, the data on recurrence were analysed using a landmark date of 6 months. This allows for all patients to have completed their treatment. However, if we look at the crude rates of local recurrence by treatment group within the 6 months following randomisation (when treatment for those receiving preoperative chemotherapy would be ongoing), there is no excess of events in the chemotherapy group (6%) compared with the surgery group (6%). This is despite 25% of all local recurrences (as first events) being recorded during this period. It should be borne in mind that patients included here have been staged using older, less accurate methods than those used today. Patients seemingly progressing on www.thelancet.com Vol 384 July 19, 2014
preoperative chemotherapy might reflect the presence of metastatic disease at the time of randomisation. In the surgery-only group, these patients would likely have been categorised as having a recurrence when in reality they should also be regarded as having progressed. These findings are based on limited data, but taken together they do not suggest an increase in the number of progressions in the chemotherapy group or operable tumours becoming inoperable during preoperative chemotherapy. Overall there is still an absolute survival improvement of 5% for patients receiving preoperative chemotherapy and this approach might allow chemosensitivity testing of the tumour to avoid ineffective treatment after surgery. There are different potential reasons for giving either preoperative or postoperative chemotherapy in this setting. Patients selected for preoperative chemotherapy are more likely to have a better prognosis than those selected for postoperative chemotherapy, because unfit patients and patients with incomplete resection would be excluded. Our research hopefully reassures those treating patients that preoperative chemotherapy is better than surgery alone with a benefit size comparable to that of postoperative chemotherapy. Further investigations of these treatments might be warranted to explore whether certain patients benefit more or less from either preoperative or postoperative chemotherapy or indeed, a combination of both. We declare no competing interests.
*Sarah Burdett, Larysa HM Rydzewska, Jayne F Tierney, Anne Auperin, Jean-Pierre Pignon, Cécile Le Pechoux, Thierry Le Chevalier, Jan van Meerbeeck [email protected] MRC Clinical Trials Unit at UCL, London WC2B 6NH, UK (SB, LHMR, JFT); Service de Biostatistique et d’Epidemiologie, Institut Gustave-Roussy, Villejuif, France (AA, J-PP, CLP, TLC); and University Hospital Antwerp, Antwerp, Belgium (JvM)
1
NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small cell lung cancer: a systematic review and metaanalysis of individual participant data. Lancet 2014; 383: 1561–71.
Standardised packaging and tobacco-industryfunded research We recently assessed the (possible) effect of plain packaging on the smoking behaviour of young Australian individuals (aged 14–17 years). 1 Our conclusion was that there is no evidence that plain packaging has lowered smoking prevalence among young Australians. Our study1 has been criticised by Anthony Laverty and colleagues (April 19, p 1384).2 They state that “in view of the short time span since the measure was introduced, the variability in the measure, and the small sample size” failing to find any evidence for a plain packaging effect “is neither an unexpected nor a meaningful conclusion”.2 On the basis of a reasoning that is not explained in sufficient detail, they further claim that a reduction of 1·25 percentage points “would be required to be statistically significant using this analysis”.2 First, any actual reduction will only turn out to be statistically significant with a certain probability, and this probability is known as the power of the test. Therefore, the authors need to attach a power (number) to the specific effect of 1·25 percentage points (unless they have a power of 1 in mind, which is unrealistic). Second, an effect as large as 1·25 percentage points is not needed to be detected with any reasonable power. For example, power against a reduction of 0·5 percentage points is about 0·65; power against a reduction of 1·0 percentage point is about 0·80; and power against a reduction of 1·25 percentage points about 0·85.1 Power of 0·8 is a commonly accepted industry standard,3 so even
Associated Press
4
233
Correspondence
the power against a reduction of only 0·5 percentage points is not unreasonably low. Laverty and colleagues1 conclude that “the lesson from Australia is that the tobacco industry’s struggle against standardised packaging will not cease and it is essential to guard against continued misrepresentation of the evidence”. The data we have worked with are publicly available, and our analyses are described in detail and can be replicated. So, which evidence is supposed to be misrepresented is unclear to us. MW and AK have received fees from Philip Morris International.
Ashok Kaul, *Michael Wolf [email protected] Saarland University, Department of Economics, 66123 Saarbrucken, Germany (AK); and University of Zurich, Department of Economics, 8032 Zurich, Switzerland (MW) For more on the Global Standardized Hypertension Treatment Project see http:// www.cdc.gov/globalhealth/ncd/ hypertension-treatment.htm
1
2
3
Kaul A, Wolf M. The (possible) effect of plain packaging on the smoking prevalence of minors in Australia: a trend analysis. Working Paper ECON 149, Department of Economics, University of Zurich. http://www.econ.uzh.ch/ static/workingpapers.php?id=828 (accessed June 26, 2014). Laverty AA, Watt HC, Arnott D, Hopkinson NS. Standardised packaging and tobacco-industryfunded research. Lancet 2014; 383: 1384. FDA. Guidance for Industry—Diabetis mellitus: Developing drugs and therapeutic biologics for treatment and prevention. 2008. http://www. fda.gov/downloads/Drugs/Guidances/ ucm071624.pdf (accessed June 26, 2014).
Getty Images, Sandeep Subba
Hypertension in populations of different ethnic origins In their recent Editorial Hypertension: an urgent need for global control and prevention (May 31, p 1861),1 the Lancet’s Editors highlight the global need to address high blood pressure— the leading risk factor for mortality worldwide. This is particularly urgent in low-income and middle-income countries where prevalence is increasing. Present treatment guidelines, however, are largely based on white populations whereas evidence suggests that cardiovascular 234
disease varies with ethnic origin.2 South Asian populations, for example, have higher death rates from ischaemic heart disease at young ages compared with Western countries; Hispanic populations might achieve better blood pressure control with less treatment compared with non-hispanic groups.3,4 Thresholds for treatment, blood pressure targets, and antihypertensive regimens might differ between ethnic groups. Despite differences in general guidelines, the Eighth Joint National Committee (JNC8), American and International Societies of Hypertension, and European Society of Hypertension/ European Society of Cardiology all provided specific recommendations for black individuals.5–7 Ethnic variations could have implications for polypills and other initiatives to streamline management in low-income and middle-income settings, such as the Global Standardized Hypertension Treatment Project. Good quality data on hypertension in different ethnic populations are missing. Of the more than 180 studies that met the JNC8’s standards for inclusion, fewer than 30 include analysis of non-white, non-black groups. 5 Generating high-quality evidence for diverse populations should become a priority. Prospective cohort studies and randomised controlled trials are needed to define how blood pressure should best be managed among the groups found in low-income and middle-income countries where the burden of hypertension is growing.
1
2
3
4
5
6
7
The Lancet. Hypertension: an urgent need for global control and prevention. Lancet 2014; 383: 1861. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation 2001; 104: 2855–64. Joshi P, Islam S, Pais P,et al. Risk factors for early myocardial infarction in South Asians compared with individuals in other countries. JAMA 2007; 297: 286–94. Cooper-DeHoff R, Aranda Jr. JM, Gaxiola E, et al. Blood pressure control and cardiovascular outcomes in high-risk Hispanic patients— Findings from the International Verapamil SR/ Trandolapril Study (INVEST). Am Heart J 2006; 151: 1072–79. James PA, Oparil S, Carter BL, et al. 2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults: Report by the Panel Appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014; 311: 507–20. Weber MA, Schiffrin EL, White WB, et al. Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension. J Clinical Hypertens 2014; 16: 14–26. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension. J Hypertens 2013; 31: 1281–57.
We declare no competing interests.
*Ranu S Dhillon, Kiran Clair, Max Fraden, Marwah Abdalla [email protected] Division of Global Health Equity, Brigham and Women’s Hospital, Boston, MA 02115, USA (RSD); Earth Institute, Columbia University, New York, NY, USA (RSD); Department of Obstetrics and Gynecology, University of California Irvine, Orange, CA, USA (KC); Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA (MF); and Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA (MA)
www.thelancet.com Vol 384 July 19, 2014
5
van Meerbeeck JP, Kramer GW, Van Schil PE, et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Inst 2007; 99: 442–50. Felip E, Rosell R, Maestre JA, et al, and the Spanish Lung Cancer Group. Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alonein early-stage nonsmall-cell lung cancer. J Clin Oncol 2010; 28: 3138–45.
Authors’ reply We thank Gerard Hanna and
colleagues for their interest in our study, 1 and agree it raises questions about the best sequence of treatments for patients with operable non-small-cell lung cancer. We found no difference in the number of complete resections between patients receiving chemotherapy compared with those receiving immediate surgery. Equally, although the numbers of patients are small, we found no increase in the number of incomplete resections for patients receiving chemotherapy, although this finding was not clearly reported. Unfortunately, with the data we have collected, we cannot reliably distinguish between disease progression and disease recurrence. As described in our paper, the data on recurrence were analysed using a landmark date of 6 months. This allows for all patients to have completed their treatment. However, if we look at the crude rates of local recurrence by treatment group within the 6 months following randomisation (when treatment for those receiving preoperative chemotherapy would be ongoing), there is no excess of events in the chemotherapy group (6%) compared with the surgery group (6%). This is despite 25% of all local recurrences (as first events) being recorded during this period. It should be borne in mind that patients included here have been staged using older, less accurate methods than those used today. Patients seemingly progressing on www.thelancet.com Vol 384 July 19, 2014
preoperative chemotherapy might reflect the presence of metastatic disease at the time of randomisation. In the surgery-only group, these patients would likely have been categorised as having a recurrence when in reality they should also be regarded as having progressed. These findings are based on limited data, but taken together they do not suggest an increase in the number of progressions in the chemotherapy group or operable tumours becoming inoperable during preoperative chemotherapy. Overall there is still an absolute survival improvement of 5% for patients receiving preoperative chemotherapy and this approach might allow chemosensitivity testing of the tumour to avoid ineffective treatment after surgery. There are different potential reasons for giving either preoperative or postoperative chemotherapy in this setting. Patients selected for preoperative chemotherapy are more likely to have a better prognosis than those selected for postoperative chemotherapy, because unfit patients and patients with incomplete resection would be excluded. Our research hopefully reassures those treating patients that preoperative chemotherapy is better than surgery alone with a benefit size comparable to that of postoperative chemotherapy. Further investigations of these treatments might be warranted to explore whether certain patients benefit more or less from either preoperative or postoperative chemotherapy or indeed, a combination of both. We declare no competing interests.
*Sarah Burdett, Larysa HM Rydzewska, Jayne F Tierney, Anne Auperin, Jean-Pierre Pignon, Cécile Le Pechoux, Thierry Le Chevalier, Jan van Meerbeeck [email protected] MRC Clinical Trials Unit at UCL, London WC2B 6NH, UK (SB, LHMR, JFT); Service de Biostatistique et d’Epidemiologie, Institut Gustave-Roussy, Villejuif, France (AA, J-PP, CLP, TLC); and University Hospital Antwerp, Antwerp, Belgium (JvM)
1
NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small cell lung cancer: a systematic review and metaanalysis of individual participant data. Lancet 2014; 383: 1561–71.
Standardised packaging and tobacco-industryfunded research We recently assessed the (possible) effect of plain packaging on the smoking behaviour of young Australian individuals (aged 14–17 years). 1 Our conclusion was that there is no evidence that plain packaging has lowered smoking prevalence among young Australians. Our study1 has been criticised by Anthony Laverty and colleagues (April 19, p 1384).2 They state that “in view of the short time span since the measure was introduced, the variability in the measure, and the small sample size” failing to find any evidence for a plain packaging effect “is neither an unexpected nor a meaningful conclusion”.2 On the basis of a reasoning that is not explained in sufficient detail, they further claim that a reduction of 1·25 percentage points “would be required to be statistically significant using this analysis”.2 First, any actual reduction will only turn out to be statistically significant with a certain probability, and this probability is known as the power of the test. Therefore, the authors need to attach a power (number) to the specific effect of 1·25 percentage points (unless they have a power of 1 in mind, which is unrealistic). Second, an effect as large as 1·25 percentage points is not needed to be detected with any reasonable power. For example, power against a reduction of 0·5 percentage points is about 0·65; power against a reduction of 1·0 percentage point is about 0·80; and power against a reduction of 1·25 percentage points about 0·85.1 Power of 0·8 is a commonly accepted industry standard,3 so even
Associated Press
4
233
Correspondence
the power against a reduction of only 0·5 percentage points is not unreasonably low. Laverty and colleagues1 conclude that “the lesson from Australia is that the tobacco industry’s struggle against standardised packaging will not cease and it is essential to guard against continued misrepresentation of the evidence”. The data we have worked with are publicly available, and our analyses are described in detail and can be replicated. So, which evidence is supposed to be misrepresented is unclear to us. MW and AK have received fees from Philip Morris International.
Ashok Kaul, *Michael Wolf [email protected] Saarland University, Department of Economics, 66123 Saarbrucken, Germany (AK); and University of Zurich, Department of Economics, 8032 Zurich, Switzerland (MW) For more on the Global Standardized Hypertension Treatment Project see http:// www.cdc.gov/globalhealth/ncd/ hypertension-treatment.htm
1
2
3
Kaul A, Wolf M. The (possible) effect of plain packaging on the smoking prevalence of minors in Australia: a trend analysis. Working Paper ECON 149, Department of Economics, University of Zurich. http://www.econ.uzh.ch/ static/workingpapers.php?id=828 (accessed June 26, 2014). Laverty AA, Watt HC, Arnott D, Hopkinson NS. Standardised packaging and tobacco-industryfunded research. Lancet 2014; 383: 1384. FDA. Guidance for Industry—Diabetis mellitus: Developing drugs and therapeutic biologics for treatment and prevention. 2008. http://www. fda.gov/downloads/Drugs/Guidances/ ucm071624.pdf (accessed June 26, 2014).
Getty Images, Sandeep Subba
Hypertension in populations of different ethnic origins In their recent Editorial Hypertension: an urgent need for global control and prevention (May 31, p 1861),1 the Lancet’s Editors highlight the global need to address high blood pressure— the leading risk factor for mortality worldwide. This is particularly urgent in low-income and middle-income countries where prevalence is increasing. Present treatment guidelines, however, are largely based on white populations whereas evidence suggests that cardiovascular 234
disease varies with ethnic origin.2 South Asian populations, for example, have higher death rates from ischaemic heart disease at young ages compared with Western countries; Hispanic populations might achieve better blood pressure control with less treatment compared with non-hispanic groups.3,4 Thresholds for treatment, blood pressure targets, and antihypertensive regimens might differ between ethnic groups. Despite differences in general guidelines, the Eighth Joint National Committee (JNC8), American and International Societies of Hypertension, and European Society of Hypertension/ European Society of Cardiology all provided specific recommendations for black individuals.5–7 Ethnic variations could have implications for polypills and other initiatives to streamline management in low-income and middle-income settings, such as the Global Standardized Hypertension Treatment Project. Good quality data on hypertension in different ethnic populations are missing. Of the more than 180 studies that met the JNC8’s standards for inclusion, fewer than 30 include analysis of non-white, non-black groups. 5 Generating high-quality evidence for diverse populations should become a priority. Prospective cohort studies and randomised controlled trials are needed to define how blood pressure should best be managed among the groups found in low-income and middle-income countries where the burden of hypertension is growing.
1
2
3
4
5
6
7
The Lancet. Hypertension: an urgent need for global control and prevention. Lancet 2014; 383: 1861. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation 2001; 104: 2855–64. Joshi P, Islam S, Pais P,et al. Risk factors for early myocardial infarction in South Asians compared with individuals in other countries. JAMA 2007; 297: 286–94. Cooper-DeHoff R, Aranda Jr. JM, Gaxiola E, et al. Blood pressure control and cardiovascular outcomes in high-risk Hispanic patients— Findings from the International Verapamil SR/ Trandolapril Study (INVEST). Am Heart J 2006; 151: 1072–79. James PA, Oparil S, Carter BL, et al. 2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults: Report by the Panel Appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014; 311: 507–20. Weber MA, Schiffrin EL, White WB, et al. Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension. J Clinical Hypertens 2014; 16: 14–26. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension. J Hypertens 2013; 31: 1281–57.
We declare no competing interests.
*Ranu S Dhillon, Kiran Clair, Max Fraden, Marwah Abdalla [email protected] Division of Global Health Equity, Brigham and Women’s Hospital, Boston, MA 02115, USA (RSD); Earth Institute, Columbia University, New York, NY, USA (RSD); Department of Obstetrics and Gynecology, University of California Irvine, Orange, CA, USA (KC); Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA (MF); and Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, NY, USA (MA)
www.thelancet.com Vol 384 July 19, 2014