Principles of epidemiological research on adverse and beneficial drug effects

The important general principles of drug epidemiological research that should be used to assess the quality and validity of studies are described.

Abstract

Several important public-health issues about drug effects have been discussed in recent articles that were based on observational (non-experimental) information. 1 Farley TMM Meirik O Chang CL Marmot MG Poulter NR Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. Lancet. 1995; 346: 1582-1588 Summary Full Text PDF PubMed Scopus (623) Google Scholar , 2 Jick H Jick SS Gurewich V Myers MW Vasilakis C Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptive with differing progestagen components. Lancet. 1995; 346: 1589-1593 PubMed Scopus (737) Google Scholar , 3 Bloemenkamp KWM Rosendaal FR Helmerhorst FM Buller HR Vandenbroucke JP Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestogen. Lancet. 1995; 346: 1593-1596 PubMed Scopus (623) Google Scholar , 4 Farmer RDT Lawrenson RA Thompson CR Kennedy JG Hambleton IR Population-based study of risk of venous thromboembolism associated with various oral contraceptives. Lancet. 1997; 349: 83-88 Summary Full Text Full Text PDF PubMed Scopus (347) Google Scholar , 5 Lidegaard O Edstrom B Kreiner S Oral contraceptives and venous thromboembolism. WHO Technical Report Series 877. WHO, Geneva1998 Google Scholar , 6 Tang MX Jacobs D Stern Y et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet. 1996; 348: 429-432 Summary Full Text Full Text PDF PubMed Scopus (1587) Google Scholar , 7 Brenner DE Kukull WA Stergachis A et al. Postmenopausal estrogen replacement therapy and the risk of Alzheimer's disease: a population-based case-control study. Am J Epidemiol. 1994; 140: 262-267 Crossref PubMed Scopus (284) Google Scholar , 8 Psaty BM Heckbert SR Koepsell TD et al. The risk of myocardial infarction association with antihypertensive therapies. JAMA. 1995; 274: 620-625 Crossref PubMed Scopus (972) Google Scholar , 9 Pahor M Guralnik JM Corti MC Foley DJ Carbonin P Havlik RJ Long-term survival and use of antihypertensive medications in older persons. J Am Geriatr Soc. 1995; 43: 1191-1197 Crossref PubMed Scopus (296) Google Scholar , 10 Jick H Derby LE Gurewich V Vasilakis C The risk of myocardial infarction associated with antihypertensive drug treatment in persons with uncomplicated essential hypertension. Pharmacotherapy. 1996; 16: 321-326 PubMed Google Scholar , 11 Pahor M Guralnik JM Ferrucci L et al. Calcium-channel blockade and incidence of cancer in aged populations. Lancet. 1996; 348: 493-497 Summary Full Text Full Text PDF PubMed Scopus (327) Google Scholar , 12 Jick H Jick SS Derby LE Vasilakis C Myers MW Meier CR Calcium channel blockers and risk of cancer. Lancet. 1997; 349: 525-528 Summary Full Text Full Text PDF PubMed Scopus (190) Google Scholar , 13 Rosenberg L Sowmya R Palmer JR et al. Calcium channel blockers and the risk of cancer. JAMA. 1998; 279: 1000-1004 Crossref PubMed Scopus (130) Google Scholar , 14 Fitzpatrick AL Daling JR Furberg CD Kronmal RA Weissfeld JL Use of calcium channel blockers and breast carcinoma risk in postmenopausal women. Cancer. 1997; 80: 1438-1447 Crossref PubMed Scopus (118) Google Scholar , 15 Pahor M Guralnik JM Furberg CD Carbonin P Havlik RJ Risk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old. Lancet. 1996; 347: 1061-1065 Summary PubMed Scopus (200) Google Scholar , 16 Lindberg G Bingefors K Ranstam J Råstam L Melander A Use of calcium channel blockers and risk of suicide: ecological findings confirmed in population based cohort study. BMJ. 1998; 316: 741-745 Crossref PubMed Scopus (62) Google Scholar , 17 Andersen K Launer LJ Ott A Hoes AW Breteler MMB Hofman A Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease?. Neurology. 1995; 45: 1441-1445 Crossref PubMed Scopus (302) Google Scholar , 18 Stewart WF Kawas C Corrada M Metter EJ Risk of Alzheimer's disease and duration of NSAID use. Neurology. 1997; 48: 626-632 Crossref PubMed Scopus (1049) Google Scholar , 19 Rich JB Rasmussen DX Folstein MF Carson KA Kawas C Brandt J Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology. 1995; 45: 51-55 Crossref PubMed Scopus (433) Google Scholar The issues include the relation of oestrogen-containing drugs, 1 Farley TMM Meirik O Chang CL Marmot MG Poulter NR Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. Lancet. 1995; 346: 1582-1588 Summary Full Text PDF PubMed Scopus (623) Google Scholar , 2 Jick H Jick SS Gurewich V Myers MW Vasilakis C Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptive with differing progestagen components. Lancet. 1995; 346: 1589-1593 PubMed Scopus (737) Google Scholar , 3 Bloemenkamp KWM Rosendaal FR Helmerhorst FM Buller HR Vandenbroucke JP Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestogen. Lancet. 1995; 346: 1593-1596 PubMed Scopus (623) Google Scholar , 4 Farmer RDT Lawrenson RA Thompson CR Kennedy JG Hambleton IR Population-based study of risk of venous thromboembolism associated with various oral contraceptives. Lancet. 1997; 349: 83-88 Summary Full Text Full Text PDF PubMed Scopus (347) Google Scholar , 5 Lidegaard O Edstrom B Kreiner S Oral contraceptives and venous thromboembolism. WHO Technical Report Series 877. WHO, Geneva1998 Google Scholar , 6 Tang MX Jacobs D Stern Y et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet. 1996; 348: 429-432 Summary Full Text Full Text PDF PubMed Scopus (1587) Google Scholar , 7 Brenner DE Kukull WA Stergachis A et al. Postmenopausal estrogen replacement therapy and the risk of Alzheimer's disease: a population-based case-control study. Am J Epidemiol. 1994; 140: 262-267 Crossref PubMed Scopus (284) Google Scholar antihypertensive agents, 8 Psaty BM Heckbert SR Koepsell TD et al. The risk of myocardial infarction association with antihypertensive therapies. JAMA. 1995; 274: 620-625 Crossref PubMed Scopus (972) Google Scholar , 9 Pahor M Guralnik JM Corti MC Foley DJ Carbonin P Havlik RJ Long-term survival and use of antihypertensive medications in older persons. J Am Geriatr Soc. 1995; 43: 1191-1197 Crossref PubMed Scopus (296) Google Scholar , 10 Jick H Derby LE Gurewich V Vasilakis C The risk of myocardial infarction associated with antihypertensive drug treatment in persons with uncomplicated essential hypertension. Pharmacotherapy. 1996; 16: 321-326 PubMed Google Scholar , 11 Pahor M Guralnik JM Ferrucci L et al. Calcium-channel blockade and incidence of cancer in aged populations. Lancet. 1996; 348: 493-497 Summary Full Text Full Text PDF PubMed Scopus (327) Google Scholar , 12 Jick H Jick SS Derby LE Vasilakis C Myers MW Meier CR Calcium channel blockers and risk of cancer. Lancet. 1997; 349: 525-528 Summary Full Text Full Text PDF PubMed Scopus (190) Google Scholar , 13 Rosenberg L Sowmya R Palmer JR et al. Calcium channel blockers and the risk of cancer. JAMA. 1998; 279: 1000-1004 Crossref PubMed Scopus (130) Google Scholar , 14 Fitzpatrick AL Daling JR Furberg CD Kronmal RA Weissfeld JL Use of calcium channel blockers and breast carcinoma risk in postmenopausal women. Cancer. 1997; 80: 1438-1447 Crossref PubMed Scopus (118) Google Scholar , 15 Pahor M Guralnik JM Furberg CD Carbonin P Havlik RJ Risk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old. Lancet. 1996; 347: 1061-1065 Summary PubMed Scopus (200) Google Scholar , 16 Lindberg G Bingefors K Ranstam J Råstam L Melander A Use of calcium channel blockers and risk of suicide: ecological findings confirmed in population based cohort study. BMJ. 1998; 316: 741-745 Crossref PubMed Scopus (62) Google Scholar and non-steroidal anti-inflammatory drugs (NSAIDs) 17 Andersen K Launer LJ Ott A Hoes AW Breteler MMB Hofman A Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease?. Neurology. 1995; 45: 1441-1445 Crossref PubMed Scopus (302) Google Scholar , 18 Stewart WF Kawas C Corrada M Metter EJ Risk of Alzheimer's disease and duration of NSAID use. Neurology. 1997; 48: 626-632 Crossref PubMed Scopus (1049) Google Scholar , 19 Rich JB Rasmussen DX Folstein MF Carson KA Kawas C Brandt J Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology. 1995; 45: 51-55 Crossref PubMed Scopus (433) Google Scholar to cardiovascular disease, 1 Farley TMM Meirik O Chang CL Marmot MG Poulter NR Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. Lancet. 1995; 346: 1582-1588 Summary Full Text PDF PubMed Scopus (623) Google Scholar , 2 Jick H Jick SS Gurewich V Myers MW Vasilakis C Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptive with differing progestagen components. Lancet. 1995; 346: 1589-1593 PubMed Scopus (737) Google Scholar , 3 Bloemenkamp KWM Rosendaal FR Helmerhorst FM Buller HR Vandenbroucke JP Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestogen. Lancet. 1995; 346: 1593-1596 PubMed Scopus (623) Google Scholar , 4 Farmer RDT Lawrenson RA Thompson CR Kennedy JG Hambleton IR Population-based study of risk of venous thromboembolism associated with various oral contraceptives. Lancet. 1997; 349: 83-88 Summary Full Text Full Text PDF PubMed Scopus (347) Google Scholar , 5 Lidegaard O Edstrom B Kreiner S Oral contraceptives and venous thromboembolism. WHO Technical Report Series 877. WHO, Geneva1998 Google Scholar , 8 Psaty BM Heckbert SR Koepsell TD et al. The risk of myocardial infarction association with antihypertensive therapies. JAMA. 1995; 274: 620-625 Crossref PubMed Scopus (972) Google Scholar , 9 Pahor M Guralnik JM Corti MC Foley DJ Carbonin P Havlik RJ Long-term survival and use of antihypertensive medications in older persons. J Am Geriatr Soc. 1995; 43: 1191-1197 Crossref PubMed Scopus (296) Google Scholar , 10 Jick H Derby LE Gurewich V Vasilakis C The risk of myocardial infarction associated with antihypertensive drug treatment in persons with uncomplicated essential hypertension. Pharmacotherapy. 1996; 16: 321-326 PubMed Google Scholar cancer, 11 Pahor M Guralnik JM Ferrucci L et al. Calcium-channel blockade and incidence of cancer in aged populations. Lancet. 1996; 348: 493-497 Summary Full Text Full Text PDF PubMed Scopus (327) Google Scholar , 12 Jick H Jick SS Derby LE Vasilakis C Myers MW Meier CR Calcium channel blockers and risk of cancer. Lancet. 1997; 349: 525-528 Summary Full Text Full Text PDF PubMed Scopus (190) Google Scholar , 13 Rosenberg L Sowmya R Palmer JR et al. Calcium channel blockers and the risk of cancer. JAMA. 1998; 279: 1000-1004 Crossref PubMed Scopus (130) Google Scholar , 14 Fitzpatrick AL Daling JR Furberg CD Kronmal RA Weissfeld JL Use of calcium channel blockers and breast carcinoma risk in postmenopausal women. Cancer. 1997; 80: 1438-1447 Crossref PubMed Scopus (118) Google Scholar Alzheimer's disease, 6 Tang MX Jacobs D Stern Y et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet. 1996; 348: 429-432 Summary Full Text Full Text PDF PubMed Scopus (1587) Google Scholar , 7 Brenner DE Kukull WA Stergachis A et al. Postmenopausal estrogen replacement therapy and the risk of Alzheimer's disease: a population-based case-control study. Am J Epidemiol. 1994; 140: 262-267 Crossref PubMed Scopus (284) Google Scholar , 17 Andersen K Launer LJ Ott A Hoes AW Breteler MMB Hofman A Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease?. Neurology. 1995; 45: 1441-1445 Crossref PubMed Scopus (302) Google Scholar , 18 Stewart WF Kawas C Corrada M Metter EJ Risk of Alzheimer's disease and duration of NSAID use. Neurology. 1997; 48: 626-632 Crossref PubMed Scopus (1049) Google Scholar , 19 Rich JB Rasmussen DX Folstein MF Carson KA Kawas C Brandt J Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology. 1995; 45: 51-55 Crossref PubMed Scopus (433) Google Scholar gastrointestinal bleeding, 15 Pahor M Guralnik JM Furberg CD Carbonin P Havlik RJ Risk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old. Lancet. 1996; 347: 1061-1065 Summary PubMed Scopus (200) Google Scholar and suicide. 16 Lindberg G Bingefors K Ranstam J Råstam L Melander A Use of calcium channel blockers and risk of suicide: ecological findings confirmed in population based cohort study. BMJ. 1998; 316: 741-745 Crossref PubMed Scopus (62) Google Scholar Most of the controversial issues relate to possible adverse drug effects 1 Farley TMM Meirik O Chang CL Marmot MG Poulter NR Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. Lancet. 1995; 346: 1582-1588 Summary Full Text PDF PubMed Scopus (623) Google Scholar , 2 Jick H Jick SS Gurewich V Myers MW Vasilakis C Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptive with differing progestagen components. Lancet. 1995; 346: 1589-1593 PubMed Scopus (737) Google Scholar , 3 Bloemenkamp KWM Rosendaal FR Helmerhorst FM Buller HR Vandenbroucke JP Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestogen. Lancet. 1995; 346: 1593-1596 PubMed Scopus (623) Google Scholar , 4 Farmer RDT Lawrenson RA Thompson CR Kennedy JG Hambleton IR Population-based study of risk of venous thromboembolism associated with various oral contraceptives. Lancet. 1997; 349: 83-88 Summary Full Text Full Text PDF PubMed Scopus (347) Google Scholar , 5 Lidegaard O Edstrom B Kreiner S Oral contraceptives and venous thromboembolism. WHO Technical Report Series 877. WHO, Geneva1998 Google Scholar , 8 Psaty BM Heckbert SR Koepsell TD et al. The risk of myocardial infarction association with antihypertensive therapies. JAMA. 1995; 274: 620-625 Crossref PubMed Scopus (972) Google Scholar , 9 Pahor M Guralnik JM Corti MC Foley DJ Carbonin P Havlik RJ Long-term survival and use of antihypertensive medications in older persons. J Am Geriatr Soc. 1995; 43: 1191-1197 Crossref PubMed Scopus (296) Google Scholar , 10 Jick H Derby LE Gurewich V Vasilakis C The risk of myocardial infarction associated with antihypertensive drug treatment in persons with uncomplicated essential hypertension. Pharmacotherapy. 1996; 16: 321-326 PubMed Google Scholar , 11 Pahor M Guralnik JM Ferrucci L et al. Calcium-channel blockade and incidence of cancer in aged populations. Lancet. 1996; 348: 493-497 Summary Full Text Full Text PDF PubMed Scopus (327) Google Scholar , 12 Jick H Jick SS Derby LE Vasilakis C Myers MW Meier CR Calcium channel blockers and risk of cancer. Lancet. 1997; 349: 525-528 Summary Full Text Full Text PDF PubMed Scopus (190) Google Scholar , 13 Rosenberg L Sowmya R Palmer JR et al. Calcium channel blockers and the risk of cancer. JAMA. 1998; 279: 1000-1004 Crossref PubMed Scopus (130) Google Scholar , 14 Fitzpatrick AL Daling JR Furberg CD Kronmal RA Weissfeld JL Use of calcium channel blockers and breast carcinoma risk in postmenopausal women. Cancer. 1997; 80: 1438-1447 Crossref PubMed Scopus (118) Google Scholar , 15 Pahor M Guralnik JM Furberg CD Carbonin P Havlik RJ Risk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old. Lancet. 1996; 347: 1061-1065 Summary PubMed Scopus (200) Google Scholar , 16 Lindberg G Bingefors K Ranstam J Råstam L Melander A Use of calcium channel blockers and risk of suicide: ecological findings confirmed in population based cohort study. BMJ. 1998; 316: 741-745 Crossref PubMed Scopus (62) Google Scholar but some relate to possible beneficial effects of drugs. 6 Tang MX Jacobs D Stern Y et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet. 1996; 348: 429-432 Summary Full Text Full Text PDF PubMed Scopus (1587) Google Scholar , 7 Brenner DE Kukull WA Stergachis A et al. Postmenopausal estrogen replacement therapy and the risk of Alzheimer's disease: a population-based case-control study. Am J Epidemiol. 1994; 140: 262-267 Crossref PubMed Scopus (284) Google Scholar , 17 Andersen K Launer LJ Ott A Hoes AW Breteler MMB Hofman A Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease?. Neurology. 1995; 45: 1441-1445 Crossref PubMed Scopus (302) Google Scholar , 18 Stewart WF Kawas C Corrada M Metter EJ Risk of Alzheimer's disease and duration of NSAID use. Neurology. 1997; 48: 626-632 Crossref PubMed Scopus (1049) Google Scholar , 19 Rich JB Rasmussen DX Folstein MF Carson KA Kawas C Brandt J Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology. 1995; 45: 51-55 Crossref PubMed Scopus (433) Google Scholar Effect of oestrogen during menopause on risk and age at onset of Alzheimer's diseaseOestrogen use in postmenopausal women may delay the onset and decrease the risk of Alzheimer's disease. Prospective studies are needed to establish the dose and duration of oestrogen required to provide this benefit and to assess its safety in elderly postmenopausal women. Full-Text PDF Open AccessProspective study of exogenous hormones and risk of pulmonary embolism in womenPrimary PE was uncommon in this cohort. The risk was increased by current though not past use of postmenopausal hormones or OCs. Full-Text PDF