European Journal of Clinical Pharmacology

, Volume 64, Issue 2, pp 115–125 | Cite as

Do we learn the right things from clinical trials?

Review Article


Added value Adverse reactions Clinical end-points Clinical drug trials Comparators Design Conflicts of interest Randomization 



The authors are indebted to Mrs. Judith Baggott for her helpful editorial assistance, to Mrs. Giuseppina Petruzzelli from the G. A. Pfeiffer Memorial Library for her help in preparing the manuscript and to Mrs. Marzia Marchesini for her careful secretarial assistance.


  1. 1.
    Chalmers I, Clarke M (2004) Commentary: the 1944 patulin trial: the first properly controlled multicentre trial conducted under the aegis of the British Medical Research Council. Int J Epidemiol 33(2):253–260PubMedCrossRefGoogle Scholar
  2. 2.
    Travis K (2005) Bernard Fisher reflects on a half-century’s worth of breast cancer research. J Natl Cancer Inst 97(22):1636–1637PubMedGoogle Scholar
  3. 3.
    Shadish WR, Cook TD, Campbell DT (2003) Experiments and generalized causal inference. Experimental and quasi-experimental designs for generalized causal inference. Houghton Mifflin, Boston, pp 1–32Google Scholar
  4. 4.
    European Parliament and the Council European Union (2004) Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency. Cited 4 June 2007
  5. 5.
    Apolone G, Joppi R, Bertele’ V, Garattini S (2005) Ten years of marketing approvals of anticancer drugs in Europe: regulatory policy and guidance documents need to find a balance between different pressures. Br J Cancer 93(5):504–509PubMedCrossRefGoogle Scholar
  6. 6.
    U.S. Food and Drug Administration (2006) US FDA’S non-inferiority stance could slow sinusitis approvals. SCRIP – World Pharmaceutical News 3193:27Google Scholar
  7. 7.
    Moher D, Dulberg CS, Wells GA (1994) Statistical power, sample size, and their reporting in randomized controlled trials. JAMA 272(2):122–124PubMedCrossRefGoogle Scholar
  8. 8.
    Garattini S, Bertele V (2007) Non-inferiority trials are unethical because they disregard patients’ interests. Lancet 370(9602):1875–1877PubMedCrossRefGoogle Scholar
  9. 9.
    World Medical Association (2000) The Declaration of Helsinki. Cited 30 August 2007
  10. 10.
    Joppi R, Bertele V, Garattini S (2005) Disappointing biotech. Br Med J 331(7521):895–897CrossRefGoogle Scholar
  11. 11.
    Barbui C, Violante A, Garattini S (2000) Does placebo help establish equivalence in trials of new antidepressants? Eur Psychiatr 15(4):268–273CrossRefGoogle Scholar
  12. 12.
    Margreiter R (2002) Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study. Lancet 359(9308):741–746PubMedCrossRefGoogle Scholar
  13. 13.
    Schieppati A, Perico N, Remuzzi G (2002) Tacrolimus and ciclosporin microemulsion in renal transplantation. Lancet 360(9335):799–800PubMedCrossRefGoogle Scholar
  14. 14.
    Fulton B, Markham A (1996) Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs 51(2):278–298PubMedCrossRefGoogle Scholar
  15. 15.
    Remuzzi G, Lesti M, Gotti E, Ganeva M, Dimitrov BD, Ene-Iordache B, Gherardi G, Donati D, Salvadori M, Sandrini S, Valente U, Segoloni G, Mourad G, Federico S, Rigotti P, Sparacino V, Bosmans JL, Perico N, Ruggenenti P (2004) Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial. Lancet 364(9433):503–512PubMedCrossRefGoogle Scholar
  16. 16.
    Geddes J, Freemantle N, Harrison P, Bebbington P (2000) Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. Br Med J 321(7273):1371–1376CrossRefGoogle Scholar
  17. 17.
    Psaty BM, Weiss NS (2007) NSAID trials and the choice of comparators–questions of public health importance. N Engl J Med 356(4):328–330PubMedCrossRefGoogle Scholar
  18. 18.
    Ioannidis JP (2005) Contradicted and initially stronger effects in highly cited clinical research. JAMA 294(2):218–228PubMedCrossRefGoogle Scholar
  19. 19.
    Jones RW, Soininen H, Hager K, Aarsland D, Passmore P, Murthy A, Zhang R, Bahra R (2004) A multinational, randomised, 12-week study comparing the effects of donepezil and galantamine in patients with mild to moderate Alzheimer’s disease. Int J Geriatr Psychiatry 19(1):58–67PubMedCrossRefGoogle Scholar
  20. 20.
    Wilcock G, Howe I, Coles H, Lilienfeld S, Truyen L, Zhu Y, Bullock R, Kershaw P (2003) A long-term comparison of galantamine and donepezil in the treatment of Alzheimer’s disease. Drugs Aging 20(10):777–789PubMedCrossRefGoogle Scholar
  21. 21.
    Courtney C, Farrell D, Gray R, Hills R, Lynch L, Sellwood E, Edwards S, Hardyman W, Raftery J, Crome P, Lendon C, Shaw H, Bentham P (2004) Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. Lancet 363(9427):2105–2115PubMedCrossRefGoogle Scholar
  22. 22.
    Cornelissen VA, Fagard RH (2005) Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors. Hypertension 46(4):667–675PubMedCrossRefGoogle Scholar
  23. 23.
    Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346(6):393–400PubMedCrossRefGoogle Scholar
  24. 24.
    Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344(18):1343–1350PubMedCrossRefGoogle Scholar
  25. 25.
    Saag KG, Choi H (2006) Epidemiology, risk factors, and lifestyle modifications for gout. Arthritis Res Ther 8[Suppl 1]:S2PubMedCrossRefGoogle Scholar
  26. 26.
    Usher-Smith JA, Ramsbottom T, Pearmain H, Kirby M (2007) Evaluation of the cost savings and clinical outcomes of switching patients from atorvastatin to simvastatin and losartan to candesartan in a Primary Care setting. Int J Clin Pract 61(1):15–23PubMedCrossRefGoogle Scholar
  27. 27.
    Pandolfini C, Bonati M (2005) A literature review on off-label drug use in children. Eur J Pediatr 164(9):552–558PubMedCrossRefGoogle Scholar
  28. 28.
    Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 288(3):321–333PubMedCrossRefGoogle Scholar
  29. 29.
    Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludlam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O’Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354(7):669–683PubMedCrossRefGoogle Scholar
  30. 30.
    Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’Sullivan MJ, Margolis KL, Ockene JK, Phillips L, Pottern L, Prentice RL, Robbins J, Rohan TE, Sarto GE, Sharma S, Stefanick ML, Van Horn L, Wallace RB, Whitlock E, Bassford T, Beresford SA, Black HR, Bonds DE, Brzyski RG, Caan B, Chlebowski RT, Cochrane B, Garland C, Gass M, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Judd H, Kooperberg CL, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Lewis CE, Limacher MC, Manson JE (2006) Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med 354(7):684–696PubMedCrossRefGoogle Scholar
  31. 31.
    Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, Margolis KL, Limacher MC, Manson JE, Parker LM, Paskett E, Phillips L, Robbins J, Rossouw JE, Sarto GE, Shikany JM, Stefanick ML, Thomson CA, Van Horn L, Vitolins MZ, Wactawski-Wende J, Wallace RB, Wassertheil-Smoller S, Whitlock E, Yano K, Adams-Campbell L, Anderson GL, Assaf AR, Beresford SA, Black HR, Brunner RL, Brzyski RGL, Ford Gass M, Hays J, Heber D, Heiss G, Hendrix SL, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Kotchen JM, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Henderson MM (2006) Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295(6):629–642PubMedCrossRefGoogle Scholar
  32. 32.
    Beresford SA, Johnson KC, Ritenbaugh C, Lasser NL, Snetselaar LG, Black HR, Anderson GL, Assaf AR, Bassford T, Bowen D, Brunner RL, Brzyski RG, Caan B, Chlebowski RT, Gass M, Harrigan RC, Hays J, Heber D, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Jackson RD, Kotchen JM, Kuller LH, LaCroix AZ, Lane DS, Langer RD, Lewis CE, Manson JE, Margolis KL, Mossavar-Rahmani Y, Ockene JK, Parker VM, Perri G, Phillips L, Prentice RL, Robbins J, Rossouw JE, Sarto GE, Stefanick ML, Van Horn L, Vitolins MZ, Wactawski-Wende J, Wallace RB, Whitlock E (2006) Low-fat dietary pattern and risk of colorectal cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295(6):643–654PubMedCrossRefGoogle Scholar
  33. 33.
    Centers for Disease Control and Prevention (2007) The health and economic effects of an aging society.
  34. 34.
    Agenzia Italiana del Farmaco, AIFA (2007) Caratteristiche generali dell’uso dei farmaci in Italia. L’uso dei farmaci in Italia. Rapporto nazionale anno 2006. Il Pensiero Scientifico Editore, Rome, pp 14–24Google Scholar
  35. 35.
    Spinewine A, Schmader KE, Barber N, Hughes C, Lapane KL, Swine C, Hanlon JT (2007) Appropriate prescribing in elderly people: how well can it be measured and optimised? Lancet 370(9582):173–184PubMedCrossRefGoogle Scholar
  36. 36.
    Mallet L, Spinewine A, Huang A (2007) The challenge of managing drug interactions in elderly people. Lancet 370(9582):185–191PubMedCrossRefGoogle Scholar
  37. 37.
    Cusack B, Nielson C, Vestal R (1997) Geriatric clinical pharmacology and therapeutics. In: Speight T, Holford N (eds) Avery’s drug treatment: a guide to the properties, choice, therapeutic use and economic value of drugs in disease management, 4th edn. Adis, Auckland, pp 173–222Google Scholar
  38. 38.
    Kinirons MT, O’Mahony MS (2004) Drug metabolism and ageing. Br J Clin Pharmacol 57(5):540–544PubMedCrossRefGoogle Scholar
  39. 39.
    Wildiers H, Highley MS, de Bruijn EA, van Oosterom AT (2003) Pharmacology of anticancer drugs in the elderly population. Clin Pharmacokinet 42(14):1213–1242PubMedCrossRefGoogle Scholar
  40. 40.
    Dear JW, Lilitkarntakul P, Webb DJ (2006) Are rare diseases still orphans or happily adopted? The challenges of developing and using orphan medicinal products. Br J Clin Pharmacol 62(3):264–271PubMedCrossRefGoogle Scholar
  41. 41.
    Psaty BM, Furberg CD (2007) Rosiglitazone and cardiovascular risk. N Engl J Med 356(24):2522–2524PubMedCrossRefGoogle Scholar
  42. 42.
    Scandinavian Simvastatin Survival Study (4S) (1994) Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344(8934):1383–1389CrossRefGoogle Scholar
  43. 43.
    Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ (1995) Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med 333(20):1301–1307PubMedCrossRefGoogle Scholar
  44. 44.
    Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2007) Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297(8):842–857PubMedCrossRefGoogle Scholar
  45. 45.
    GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico) (1999) Dietary supplementation with –3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet 354(9177):447–455CrossRefGoogle Scholar
  46. 46.
    GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico) (1986) Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico (GISSI). Lancet 1(8478):397–402Google Scholar
  47. 47.
    ISIS-2 (Second International Study of Infarct Survival) Collaborative Group (1988) Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet 2(8607):349–360Google Scholar
  48. 48.
    Antiplatelet Trialists’ Collaboration (1994) Collaborative overview of randomised trials of antiplatelet therapy – I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists’ Collaboration. BMJ 308(6921):81–106Google Scholar
  49. 49.
    GISEN (Gruppo Italiano di Studi Epidemiologici in Nefrologia) (1997) Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet 349(9069):1857–1863CrossRefGoogle Scholar
  50. 50.
    Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329(20):1456–1462PubMedCrossRefGoogle Scholar
  51. 51.
    Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, Ponticelli C, Ritz E, Zucchelli P (1996) Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med 334(15):939–945PubMedCrossRefGoogle Scholar
  52. 52.
    Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, Salvadori M, Scolari F, Schena FP, Remuzzi G (1999) Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 354(9176):359–364PubMedCrossRefGoogle Scholar
  53. 53.
    Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G (1998) Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy. Lancet 352(9136):1252–1256PubMedCrossRefGoogle Scholar
  54. 54.
    Remuzzi A, Gagliardini E, Sangalli F, Bonomelli M, Piccinelli M, Benigni A, Remuzzi G (2006) ACE inhibition reduces glomerulosclerosis and regenerates glomerular tissue in a model of progressive renal disease. Kidney Int 69(7):1124–1130PubMedCrossRefGoogle Scholar
  55. 55.
    Freemantle N, Calvert N (2007) Composite and surrogate outcomes in randomised controlled trials. Br Med J 334(7597):756–757CrossRefGoogle Scholar
  56. 56.
    Lapostolle F, Catineau J, Lapandry C, Adnet F (2007) Endpoints in studies on myocardial infarction. Lancet 369(9571):1430PubMedCrossRefGoogle Scholar
  57. 57.
    DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication), Gerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, Hanefeld M, Hoogwerf B, Laakso M, Mohan V, Shaw J, Zinman B, Holman RR (2006) Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 368(9541):1096–1105PubMedCrossRefGoogle Scholar
  58. 58.
    Ferreira-Gonzalez I, Busse JW, Heels-Ansdell D, Montori VM, Akl EA, Bryant DM, Alonso-Coello P, Alonso J, Worster A, Upadhye S, Jaeschke R, Schunemann HJ, Permanyer-Miralda G, Pacheco-Huergo V, Domingo-Salvany A, Wu P, Mills EJ, Guyatt GH (2007) Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials. Br Med J 334(7597):786CrossRefGoogle Scholar
  59. 59.
    Decullier E, Lheritier V, Chapuis F (2005) Fate of biomedical research protocols and publication bias in France: retrospective cohort study. Br Med J 331(7507):19CrossRefGoogle Scholar
  60. 60.
    Stern JM, Simes RJ (1997) Publication bias: evidence of delayed publication in a cohort study of clinical research projects. Br Med J 315(7109):640–645Google Scholar
  61. 61.
    Melander H, Ahlqvist-Rastad J, Meijer G, Beermann B (2003) Evidence b(i)ased medicine–selective reporting from studies sponsored by pharmaceutical industry: review of studies in new drug applications. Br Med J 326(7400):1171–1173CrossRefGoogle Scholar
  62. 62.
    Chan AW, Hrobjartsson A, Haahr MT, Gotzsche PC, Altman DG (2004) Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. JAMA 291(20):2457–2465PubMedCrossRefGoogle Scholar
  63. 63.
    Schwartz LM, Woloshin S, Dvorin EL, Welch HG (2006) Ratio measures in leading medical journals: structured review of accessibility of underlying absolute risks. Br Med J 333(7581):1248CrossRefGoogle Scholar
  64. 64.
    Mueller PS, Montori VM, Bassler D, Koenig BA, Guyatt GH (2007) Ethical issues in stopping randomized trials early because of apparent benefit. Ann Intern Med 146(12):878–881PubMedGoogle Scholar
  65. 65.
    Montori VM, Devereaux PJ, Adhikari NK, Burns KE, Eggert CH, Briel M, Lacchetti C, Leung TW, Darling E, Bryant DM, Bucher HC, Schunemann HJ, Meade MO, Cook DJ, Erwin PJ, Sood A, Sood R, Lo B, Thompson CA, Zhou Q, Mills E, Guyatt GH (2005) Randomized trials stopped early for benefit: a systematic review. JAMA 294(17):2203–2209PubMedCrossRefGoogle Scholar
  66. 66.
    Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, Robidoux A, Bevers TB, Kavanah MT, Atkins JN, Margolese RG, Runowicz CD, James JM, Ford LG, Wolmark N (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 97(22):1652–1662PubMedCrossRefGoogle Scholar
  67. 67.
    Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90(18):1371–1388PubMedCrossRefGoogle Scholar
  68. 68.
    Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ (2000) Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 343(21):1520–1528PubMedCrossRefGoogle Scholar
  69. 69.
    Juni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M (2004) Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet 364(9450):2021–2029PubMedCrossRefGoogle Scholar
  70. 70.
    Hunter RH, Joy CB, Kennedy E, Gilbody SM, Song F (2007) Risperidone versus typical antipsychotic medication for schizophrenia. Cochrane Library Issue 3.Google Scholar
  71. 71.
    Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353(12):1209–1223PubMedCrossRefGoogle Scholar
  72. 72.
    Koro CE, Fedder DO, L’Italien GJ, Weiss SS, Magder LS, Kreyenbuhl J, Revicki DA, Buchanan RW (2002) Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. Br Med J 325(7358):243CrossRefGoogle Scholar
  73. 73.
    Fontaine KR, Heo M, Harrigan EP, Shear CL, Lakshminarayanan M, Casey DE, Allison DB (2001) Estimating the consequences of anti-psychotic induced weight gain on health and mortality rate. Psychiatry Res 101(3):277–288PubMedCrossRefGoogle Scholar
  74. 74.
    Kjaergard LL, Als-Nielsen B (2002) Association between competing interests and authors’ conclusions: epidemiological study of randomised clinical trials published in the BMJ. Br Med J 325(7358):249CrossRefGoogle Scholar
  75. 75.
    Cho MK, Bero LA (1996) The quality of drug studies published in symposium proceedings. Ann Intern Med 124(5):485–489PubMedGoogle Scholar
  76. 76.
    Baker CB, Johnsrud MT, Crismon ML, Rosenheck RA, Woods SW (2003) Quantitative analysis of sponsorship bias in economic studies of antidepressants. Br J Psychiatry 183:498–506.PubMedCrossRefGoogle Scholar
  77. 77.
    Drazen JM, Curfman GD (2002) Financial associations of authors. N Engl J Med 346(24):1901–1902PubMedCrossRefGoogle Scholar
  78. 78.
    De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, Kotzin S, Laine C, Marusic A, Overbeke AJ, Schroeder TV, Sox HC, Van Der Weyden MB (2004) Clinical trial registration: a statement from the International Committee of Medical Journal Editors. Ann Intern Med 141(6):477–478PubMedGoogle Scholar
  79. 79.
    Gazzetta Ufficiale della Repubblica Italiana (2003) Capo IV. Accordo Stato-Regioni in materia sanitaria. Art. 48: Tetto di spesa per l’assistenza farmaceutica. Supplemento Ordinario n.274 (Parte prima, martedi’ 25 novembre):95–98Google Scholar
  80. 80.
    Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366(9493):1267–1278PubMedCrossRefGoogle Scholar
  81. 81.
    Chiodini BD, Franzosi MG, Barlera S, Signorini S, Lewis CM, D’Orazio A, Mocarelli P, Nicolis E, Marchioli R, Tognoni G (2007) Apolipoprotein E polymorphisms influence effect of pravastatin on survival after myocardial infarction in a Mediterranean population: the GISSI-Prevenzione study. Eur Heart J 28(16):1977–1983PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.“Mario Negri” Institute for Pharmacological ResearchMilanItaly

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