Advertisement

Special Considerations in Research

  • C. Michael White
  • Jeffrey Kluger
  • Jessica Song

Cardiovascular research is addressed in this chapter as a special therapeutics area, especially given its different and unique study needs and designs, the many indications for use of the products, the extensive pharmaceutical markets in patient numbers and sales potential, and the many products that exist and are investigational agents.

Keywords

Maximum Tolerate Dose Brief Psychiatric Rate Scale Pediatric Study Advance Cardiac Life Support Pediatric Trial 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

1 References

  1. 1.
    American Heart Association. Heart disease and stroke statistics. www.americanheart.org/statistics/index.html
  2. 2.
    American Heart Association, 2003 ACC/AHA Guidelines for CHF. Available at http:www.acc.org/clinical/guidelines.
  3. 3.
    Lamberti MJ (ed). State of the Clinical Trials Industry. A Sourcebook of charts and statistics. Thomson CenterWatch, Boston, MA, 2005.Google Scholar
  4. 4.
    Patrons C. Platelet-active drugs. Chest 1998;114:470s–8s.CrossRefGoogle Scholar
  5. 5.
    White CM. Dyslipidemias. In: PSAP, 5th Edition. ACCP, Kansas City, MO, 2004:16590.Google Scholar
  6. 6.
    Song JC, White CM. Pharmacologic, pharmacokinetic, and therapeutic differences among angiotensin II receptor antagonists. Pharmacotherapy. 2000 Feb;20(2):130–9. Review.PubMedCrossRefGoogle Scholar
  7. 7.
    Song JC, White CM. Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207–24. Review.PubMedCrossRefGoogle Scholar
  8. 8.
    White CM. Pharmacologic, pharmacokinetic, and therapeutic differences among ACE inhibitors. Pharmacotherapy 1998;18:588–99.PubMedGoogle Scholar
  9. 9.
    Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F, Smith R, Dunkman WB, Loeb H, Wong M, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. 1991 Aug 1; 325(5):303–10.PubMedCrossRefGoogle Scholar
  10. 10.
    Antman EM, McCabe CH, Gurfinkel EP, Turpie AG, Bernink PJ, Salein D, Bayes De Luna A, Fox K, Lablanche JM, Radley D, Premmereur J, Braunwald E. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial. Circulation. 1999 Oct 12;100(15):1593–601.PubMedGoogle Scholar
  11. 11.
    Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M. Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 Apr 3;348(14):1309–21. Epub 2003 Mar 31. Erratum in: N Engl J Med. 2003 May 29;348(22):2271.Google Scholar
  12. 12.
    Colucci WS, Packer M, Bristow MR, Gilbert EM, Cohn JN, Fowler MB, Krueger SK, Hershberger R, Uretsky BF, Bowers JA, Sackner-Bernstein JD, Young ST, Holcslaw TL, Lukas MA. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. US Carvedilol Heart Failure Study Group. Circulation. 1996 Dec 1;94(11):2800–6.PubMedGoogle Scholar
  13. 13.
    Sander S, White CM. Ximelagatran: a new oral anticoagulant. Formulary 2004;39:398–404.Google Scholar
  14. 14.
    Wallentin L, Wilcox RG, Weaver WD, Emanuelsson H, Goodvin A, Nystrom P, Bylock A; ESTEEM Investigators. Oral ximelagatran for secondary prophylaxis after myocardial infarction: the ESTEEM randomised controlled trial. Lancet. 2003 Sep 6; 362(9386):789–97.PubMedCrossRefGoogle Scholar
  15. 15.
    Chronic heart failure in the adult. ACC/AMA 2005 guideline update. Available at www.acc.org/quality and science/clinical/topic.htm#guidelines
  16. 16.
    White CM, Giri S, Tsikouris JP, Dunn A, Felton K, Reddy P, Kluger J. A comparison of two individual amiodarone regimens to placebo in open heart surgery patients. Ann Thorac Surg. 2002 Jul;74(1):69–74.PubMedCrossRefGoogle Scholar
  17. 17.
    White CM, Caron MF, Kalus JS, et al. Intravenous plus oral amiodarone, atrial pacing, or both strategies to prevent post-cardiothoracic surgery atrial fibrillation: the Atrial Fibrillation Suppression trial II (AFIST II). Circulation 2003;108(suppl. II): II-200–6Google Scholar
  18. 18.
    Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H; LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002 Mar 23;359(9311):995–1003.PubMedCrossRefGoogle Scholar
  19. 19.
    Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I; Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001 Sep 20;345(12):851–60.PubMedCrossRefGoogle Scholar
  20. 20.
    Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 6: advanced cardiovascular life support: 7C: a guide to the International ACLS algorithms. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation 2000;102:II42–57.Google Scholar
  21. 21.
    Grundy SM, Cleeman JI, Merz CNB, et al., for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227–39.PubMedCrossRefGoogle Scholar
  22. 22.
    Chobanian AV, Bakris GL, Black HR, et al. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206–52.PubMedCrossRefGoogle Scholar
  23. 23.
    Candesartan (Atacand®) prescribing information. AstraZeneca LP, Wilmington, DE, 2004.Google Scholar
  24. 24.
    Giri S, White CM, Dunn AB, et al. Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial. Lancet 2001;357:830–6.PubMedCrossRefGoogle Scholar
  25. 25.
    The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981–97.CrossRefGoogle Scholar
  26. 26.
    Cannon CP, Braunwald E, McCabe CH, et al., for the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495–504.PubMedCrossRefGoogle Scholar
  27. 27.
    Vidt DG, White WB, Ridley E, et al. CLAIM Study Investigators. A forced titration study of antihypertensive efficacy of candesartan cilexetil in comparison to losartan: CLAIM Study. J Hum Hypertens 2001;15:475–80.PubMedCrossRefGoogle Scholar
  28. 28.
    Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med 1999;341:871–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. The American Heart Association in Collaboration with the International Liaison Committee on Resuscitation. Circulation 2000;102 (Suppl 1): 1–384.Google Scholar
  30. 30.
    Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators; Van De Werf F, Adgey J, Ardissino D, Armstrong PW, Aylward P, Barbash G, Betriu A, Binbrek AS, Califf R, Diaz R, Fanebust R, Fox K, Granger C, Heikkila J, Husted S, Jansky P, Langer A, Lupi E, Maseri A, Meyer J, Mlczoch J, Mocceti D, Myburgh D, Oto A, Paolasso E, Pehrsson K, Seabra-Gomes R, Soares-Piegas L, Sugrue D, Tendera M, Topol E, Toutouzas P, Vahanian A, Verheugt F, Wallentin L, White H. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet. 1999 Aug 28;354(9180):716–22.CrossRefGoogle Scholar
  31. 31.
    Pfeffer MA, McMurray JJV, Velazquez EJ, et al., for the Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349:1893–906.PubMedCrossRefGoogle Scholar
  32. 32.
    Jones B, Jarvis P, Lewis JA, Ebbutt AF. Trials to assess equivalence: the importance of rigorous methods. BMJ 1996;313:36–9.PubMedGoogle Scholar
  33. 33.
    Fibrinolytic Therapy Trialists' (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1000 patients. Lancet 1994;343:311–22.Google Scholar
  34. 34.
    Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet 1999;354:716–22.CrossRefGoogle Scholar
  35. 35.
    Kober L, Torp-Pedersen C, Carlsen JE, et al., for the Trandolapril Cardiac Evaluation (TRACE) Study Group. A clinical trial of the angiotensin–converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 1995;333:1670–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Pfeffer MA, Braunwald E, Moye LA, et al. on Behalf of the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the survival and ventricular enlargement trial. N Engl J Med 1992;327:669–77.PubMedCrossRefGoogle Scholar
  37. 37.
    The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993;342:821–8.Google Scholar
  38. 38.
    McBride BF, White CM. Acute decompensated heart failure: a contemporary approach to pharmacotherapeutic management. Pharmacotherapy 2003;23:997–1020.PubMedCrossRefGoogle Scholar
  39. 39.
    White CM. Prevention of suboptimal beta-blocker treatment in patients with myocardial infarction. Ann Pharmacother. 1999 Oct;33(10):1063–72. Review.PubMedCrossRefGoogle Scholar
  40. 40.
    The GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329:673–82.CrossRefGoogle Scholar
  41. 41.
    International Joint Efficacy Comparison of Thrombolytics. Randomised, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence. Lancet 1995;346:329–36.CrossRefGoogle Scholar
  42. 42.
    Publication Committee for the VMAC (Vasodilatation in the Management of Acute CHF). Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 2002;287:1531–40.CrossRefGoogle Scholar
  43. 43.
    Cuffe MS, Califf RM, Adams KF, et al. Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) Investigators. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA 2002;287: 1541–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Black HR, Bakris GL, Elliott WJ. Hypertension: epidemiology, pathophysiology, diagnosis and treatment. In: Hurst's: The Heart, 10th ed. McGraw-Hill, New York, 2001:1553–1604.Google Scholar
  45. 45.
    Reisin E, Huth MM, Nguyen BP, Weed SG, Gonzalez FM. Intravenous fenoldopam versus sodium nitroprusside in patients with severe hypertension. Hypertension 1990; 15(suppl 1):I–59–I–62.Google Scholar
  46. 46.
    Tumlin JA, Dunbar LM, Oparil S, et al. Fenoldopam, a dopamine agonist, for hypertensive emergency: a multicenter randomized trial. Fenoldopam Study Group. Acad Emerg Med 2000;7:653–62.PubMedCrossRefGoogle Scholar
  47. 47.
    Hirschl MM, Binder M, Bur A, Herkner H, Mullner M, Woisetschlager L. Safety and efficacy of urapidil and sodium nitroprusside in the treatment of hypertensive emergencies. Intensive Care Med 1997;23:885–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Daoud EG, Strickberger SA, Man CK, et al. Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery. N Engl J Med 1997;337:1785–91.PubMedCrossRefGoogle Scholar
  49. 49.
    Meneveau N, Schiele F, Metz D, et al. Comparative efficacy of a two-hour regimen of streptokinase versus alteplase in acute massive pulmonary embolism: immediate clinical and hemodynamic outcome and one-year follow-up. J Am Coll Cardiol 1998;31: 1057–63.PubMedCrossRefGoogle Scholar
  50. 50.
    Jerjes-Sanchez C, Ramirez-Rivera A, Arriaga-Nava R, et al. High dose and short-term streptokinase infusion in patients with pulmonary embolism: prospective with seven-year follow-up trial. J Thromb Thrombolysis 2001;12:237–47.PubMedCrossRefGoogle Scholar
  51. 51.
    Sors H, Pacouret G, Azarian R, Meyer G, Charbonnier B, Simonneau G. Hemodynamic effects of bolus vs 2-h infusion of alteplase in acute massive pulmonary embolism. A randomized controlled multicenter trial. Chest 1994;106:712–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Meyer G, Sors H, Charbonnier B, et al. Effects of intravenous urokinase versus alteplase on total pulmonary resistance in acute massive pulmonary embolism: a European multicenter double-blind trial. The European Cooperative Study Group for Pulmonary Embolism. J Am Coll Cardiol 1992;19:239–45.PubMedCrossRefGoogle Scholar
  53. 53.
    Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (Stellar* Trial). Am J Cardiol 2003;89:152–60.CrossRefGoogle Scholar
  54. 54.
    The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991 Aug 1;325(5):293–302.CrossRefGoogle Scholar
  55. 55.
    Product information. Pravachol. Bristol-Myers Squibb, Princeton, NJ, 2003.Google Scholar
  56. 56.
    Product information. Crestor. AstraZeneca Pharmaceuticals LP., Wilmington, DE, 2003.Google Scholar
  57. 57.
    Product information. Lescol. Novartis Pharmaceuticals, East Hanover, NJ, 2002.Google Scholar
  58. 58.
    Product information. Lipitor. Parke-Davis (Pfizer), Parsippany, NJ, 2004.Google Scholar
  59. 59.
    Product information. Zocor. Merck & Co., White House Station, NJ, 2004.Google Scholar
  60. 60.
    Product information. Mevacor. Merck & Co., White House Station, NJ, 2002.Google Scholar
  61. 61.
    Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study) Am J Cardiol. 1998 Mar 1;81(5):582–7. Erratum in: Am J Cardiol 1998 Jul 1;82(1):128.Google Scholar
  62. 62.
    Karalis DG, Ross AM, Vacari RM, et al. Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary heart disease. Am J Cardiol 2002; 89: 667–71.PubMedCrossRefGoogle Scholar
  63. 63.
    Van Dam MJ, Penn HJAM, Hartog FR, et al. A comparison of the efficacy and tolerability of titrate-to-goal regimens of simvastatin and fluvastatin: a randomized, double-blind study in adult patients at moderate to high risk for cardiovascular disease. Clin Ther 2001;23:467–78.PubMedCrossRefGoogle Scholar
  64. 64.
    Insull W, Kafonek S, Goldner D, et al. Comparison of efficacy and safety of atorvastatin (10 mg) with simvastatin (10 mg) at six weeks. Am J Cardiol 2001;87:554–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Farnier M, Portal JJ, Pascal M. Efficacy of atorvastatin compared with simvastatin in patients with hypercholesterolemia. J Cardiovasc Pharmacol Ther 2000;5:27–32.PubMedCrossRefGoogle Scholar
  66. 66.
    Ballantyne CM, McKenney J, Trippe BS. Efficacy and safety of an extended-release formulation of fluvastatin for once-daily treatment of primary hypercholesterolemia. Am J Cardiol 2000;86:759–63.PubMedCrossRefGoogle Scholar
  67. 67.
    Mogensen CE, Neldam S, Tikkanen I, et al. for the CALM study group. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 2000;321: 1440–4.PubMedCrossRefGoogle Scholar
  68. 68.
    Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20, 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7–22.CrossRefGoogle Scholar
  69. 69.
    Kalus JS, Nappi JM. Role of race in the pharmacotherapy of heart failure. Ann Pharmacother 2002;36:471–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Exner DV, Dries DL, Domanski MJ, Cohn JN. Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N Engl J Med 2001;344:1351–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Chow MSS, White CM, Lau CP, Fan C, Tang MO. Evaluation of CYP2D6 oxidation of dextromethorphan and propafenone in a Chinese population with atrial fibrillation. J Clin Pharmacol 2001;41:92–96.PubMedCrossRefGoogle Scholar
  72. 72.
    Taylor AL, Ziesche S, Yancy C, Carson P, D'Agostino R, Ferdinand H, et al.; African-American Heart Failure Trial Investigators. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004;351:2049–5.PubMedCrossRefGoogle Scholar
  73. 73.
    Carson P, Ziesche S, Johnson G, Cohn JN. Racial differences in response to therapy for heart failure: analysis of the Vasodilator-Heart Failure Trials. J Card Fail 1999;5:178–87.PubMedCrossRefGoogle Scholar
  74. 74.
    The Beta-Blocker Evaluation of Survival Trial Investigators. A trial of the beta-blocker bucindolol in patients with advanced heart failure. N Engl J Med 2001;344:1659–67.CrossRefGoogle Scholar
  75. 75.
    Hare JM. Nitroso-redox balance in the cardiovascular system. N Engl J Med 2004;351:2112–2114.PubMedCrossRefGoogle Scholar
  76. 76.
    Abernethy DR, Flockhart DA. Molecular basis of cardiovascular drug metabolism: implications for predicting clinically important drug interactions. Circulation 2000;101:1749–53.PubMedGoogle Scholar
  77. 77.
    Tanigawara Y. Role of p-glycoprotein in drug disposition. Ther Drug Monitor 2000;22:137–40.CrossRefGoogle Scholar
  78. 78.
    Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004;350:1013–22.PubMedCrossRefGoogle Scholar
  79. 79.
    Kanazawa H, Okada A, Higaki M, Yokota H, Mashige F, Nakahara K. Stereospecific analysis of omeprazole in human plasma as a probe for CYP2C19 phenotype. J Pharm Biomed Anal 2003;30:1817–24.PubMedCrossRefGoogle Scholar
  80. 80.
    Goldstein JA. Clinical relevance of genetic polymorphisms in the human CYP2C subfamily. Br J Clin Pharmacol 2001;52:349–55.PubMedCrossRefGoogle Scholar
  81. 81.
    Yamada S, Onda M, Kato S, et al. Genetic differences in CYP2C19 single nucleotide polymorphisms among four Asian populations. J Gastroenterol 2001;36:669–72.PubMedCrossRefGoogle Scholar
  82. 82.
    Parker RB, Yates CR, Soberman JE, Laizure SC. Effects of grapefruit juice on intestinal p-glycoprotein: evaluation using digoxin in humans. Pharmacotherapy 2003;23:979–87.PubMedCrossRefGoogle Scholar
  83. 83.
    De Ponti F, Poluzzi E, Cavalli A, Recanatini M, Montanaro N. Safety of non-antiarrhythmic drugs that prolong the QT interval or induce torsades de pointes: an overview. Drug Safety 2002;25:263–86.PubMedCrossRefGoogle Scholar
  84. 84.
    Owens RC. Risk assessment for antimicrobial agent-induced QT interval prolongation and torsades de pointes. Pharmacotherapy 2001;21:301–19.PubMedCrossRefGoogle Scholar
  85. 85.
    Malik M, Camm AJ. Evaluation of drug-induced QT interval prolongation: implications for drug approval and labelling. Drug Safety 2001;24:323–51.PubMedCrossRefGoogle Scholar
  86. 86.
    Kang J, Wang L, Chen X-L, Triggle DJ, Rampe D. Interactions of a series of fluoroquinolone antibacterial drugs with human cardiac K+ channel HERG. Mol Pharmacol 2001;59:122–6.PubMedGoogle Scholar
  87. 87.
    Bischoff U, Schmidt C, Netzer R, Pongs O. Effects of fluoroquinolones on HERG currents. Eur J Pharmacol 2000;406:341–43.PubMedCrossRefGoogle Scholar
  88. 88.
    Anderson ME, Mazur A, Yang T, Roden DM. Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics. J Pharmacol Exp Ther 2001;296:806–10.PubMedGoogle Scholar
  89. 89.
    White CM. HMG CoA reductase inhibitor-induced muscle toxicity: risks, monitoring, and management. Formulary 2002;37:588–93.Google Scholar
  90. 90.
    Finch C. Rifampin and rifabutin drug interactions: an update. Arch Intern Med 2002;162:985–92.PubMedCrossRefGoogle Scholar
  91. 91.
    Jacobsen P, Andersen S, Rossing K, Jensen BR, Parving HH. Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy. Kidney Int 2003;63:1874–80.PubMedCrossRefGoogle Scholar
  92. 92.
    Caron MF, Kluger J, Tsikouris JP, Ritvo A, Kalus JS, White CM. Effects of intravenous magnesium sulfate on the QT interval in patients receiving ibutilide. Pharmacotherapy 2003;23:296–300.PubMedCrossRefGoogle Scholar
  93. 93.
    Winter ME. Clearance. In: Koda-Kimble MA, ed. Basic Clinical Pharmacokinetics, 3rd ed. Applied Therapeutics, Inc. Vancouver, 1994:26–36.Google Scholar
  94. 94.
    Newman CB, Palmer G, Silbershatz H, Szarek M. Safety of atorvastatin derived from analysis of 44 completed trials in 9416 patients. Am J Cardiol 2003;92:670–6.PubMedCrossRefGoogle Scholar
  95. 95.
    Rosenson RS. Current overview of statin-induced myopathy. Am J Med 2004;116:408–16.PubMedCrossRefGoogle Scholar
  96. 96.
    Jamal SM, Eisenberg MJ, Christopoulos S. Rhabdomyolysis associated with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am Heart J 2004;147:956–65.PubMedCrossRefGoogle Scholar
  97. 97.
    Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA 2003;289:1681–90.PubMedCrossRefGoogle Scholar
  98. 98.
    Product information. Zocor. Merck & Co., White House Station, NJ, 2004.Google Scholar
  99. 99.
    Kalus JS, Mauro VF. Dofetilide: a class III-specific antiarrhythmic agent. Ann Pharmacother 2000;34:44–56.PubMedCrossRefGoogle Scholar
  100. 100.
    Product information. Tikosyn. Pfizer Pharmaceuticals, New York, 2004.Google Scholar
  101. 101.
    Hirsh J, Raschke R. Heparin and low-molecular-weight heparin. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:188S–203S.PubMedCrossRefGoogle Scholar
  102. 102.
    Product information. Lovenox. Aventis Pharmaceuticals Inc., Bridgewater, NJ, 2004.Google Scholar
  103. 103.
    Product information. Fragmin. Pharmacia & Upjohn Company, Kalamazoo, MI, 2004.Google Scholar
  104. 104.
    Product information. Innohep. Pharmion Corp, Boulder, CO, 2003.Google Scholar

2 References

  1. 1.
    Spellberg, B.; Powers, J.H.; Brass, E.P.; Miller, L.G.; Edwards, Jr., J.E. Trends in Antimicrobial Drug Development: Implications for the Future. Clin. Infect. Dis. 2004;38(9):1279–1286.PubMedCrossRefGoogle Scholar
  2. 2.
    CDER Drug and Biologic Approved Reports. U.S. Food and Drug Administration. Dec. 2004. Available at www.fda.gov.
  3. 3.
    Linezolid, Zyvox® Product Information. Pfizer, 2004.Google Scholar
  4. 4.
    Daptomycin, Cubicin® Product Information. Cubist Pharmaceuticals, 2003.Google Scholar
  5. 5.
    Lamberti MJ. An Industry in Evolution, 4th ed. Thomson CenterWatch, Boston, MA, 2003.Google Scholar
  6. 6.
    Projan, S.J. Why Is Big Pharma Getting Out of Antibacterial Drug Discovery? Curr. Opin. Microbiol. 2003;6:427–430.PubMedCrossRefGoogle Scholar
  7. 7.
    Thompson, C.J.; Power, E.; Ruebsamen-Waigmann, H.; Labischinski, H. Antibacterial Research and Development in the 21st Century—An Industry Perspective of the Challenges. Curr. Opin. Microbiol. 2004;7:445–450.CrossRefGoogle Scholar
  8. 8.
    Wenzel, R.P.; The Antibiotic Pipeline—Challenges, Costs and Values. N. Engl. J. Med. 2004;351(6):523–526.PubMedCrossRefGoogle Scholar
  9. 9.
    Seppela, H.; Klaukka, T.; Vuopio-Varkila, J. et al. The Effect of Changes in the Consumption of Macrolide Antibiotics on Erythromycin Resistance in Group A Streptococci in Finland. N. Engl. J. Med. 1997;337:441–446.CrossRefGoogle Scholar
  10. 10.
    Bax, R.; Mullan, N.; Verhoef, J. The Millenium Bugs—The Need for and Development of New Antibacterials. Int. J. Antimicrob. Agents 2000;16:51–59.PubMedCrossRefGoogle Scholar
  11. 11.
    Livermore, D.M. Antibiotic resistance in staphylococci. Int. J. Antimicrob. Agents 2000;16:3–10.CrossRefGoogle Scholar
  12. 12.
    Lowy, F.D. Staphylococcus aureus infections. N. Engl. J. Med. 1998;339:520–532. CDC. MMWR. 1997;46:624–628, 635.Google Scholar
  13. 13.
    NNIS Antimicrobial Resistance Surveillance Report. 1999. Available at www.cdc.gov/ncidod/hip/NNIS/AR_Surv1198.htm.
  14. 14.
    Martone, W.J. Spread of vancomycin-resistant enterococci; why did it happen in the United States. Infect. Control Hosp. Epidemol. 1998;19(8):539–545.CrossRefGoogle Scholar
  15. 15.
    Bush, K. Antibacterial Drug Discovery in the 21st Century. Clin. Microbiol. Infect. 2004;10(Suppl. 4):10-17.PubMedCrossRefGoogle Scholar
  16. 16.
    Powers, J.H. Antimicrobial Drug Development—The Past, the Present, and the Future. Clin. Microbiol. Infect. 2004;10(Suppl. 4): 23–31.PubMedCrossRefGoogle Scholar
  17. 17.
    Projan, S.J.; Shlaes, D.M. Antibacterial Drug Discovery: Is It All Downhill From Here? Clin. Microbiol. Infect. 2004;10(Suppl. 4): 18–22.PubMedCrossRefGoogle Scholar
  18. 18.
    Gootz, T.D. Discovery and Development of New Antimicrobial Agents. Clin. Microbiol. Rev. 1990;3(1):13–31.PubMedGoogle Scholar
  19. 19.
    Coates, A.; Hu, Y.; Bax, R.; Page, C. The Future Challenges Facing the Development of New Antimicrobial Drugs. Nat. Rev. 2002;1:895–910.Google Scholar
  20. 20.
    Office of Drug Evaluation IV, Center for Drug Evaluation and Research, FDA/IDSA/ISAP Workshop, April 16, 2004.Google Scholar
  21. 21.
    Available at www.idsociety.org.

3 References

  1. 1.
    Anonymous. Oncology, market indicators. Nat Rev Drug Discov 2005 (May Suppl):S19.Google Scholar
  2. 2.
    Humphreys A, Mayer R. 11th Annual Report: World's best selling medicines. Med Ad News 2005;24(5):1, 24–37.Google Scholar
  3. 3.
    King J. Top 10 areas of research. 5th annual report. R&D Directions 2004;10(9):36–43.Google Scholar
  4. 4.
    SEER Surveillance, Epidemiology and End Results. Stat database: incidences and mortality in U.S. (1992, 2002), National Cancer Institute, 2005.Google Scholar
  5. 5.
    Eisenhauer EA, O'Dwyer PJ, Christian M, et al. Phase I clinical trial design in cancer drug development. J Clin Oncol 2000, 18: 684–692.PubMedGoogle Scholar
  6. 6.
    Simon R, Freidlin B, Rubinstein L, et al. Accelerated titration designs for phase I clinical trials in oncology. J Natl Cancer Inst 1997;89:1138–1147.PubMedCrossRefGoogle Scholar
  7. 7.
    Collins JM, Grieshaber CK, Chabner BA. Pharmacologically guided phase I trials based upon preclinical development. J Natl Cancer Inst 1990;82:1321–1326.PubMedCrossRefGoogle Scholar
  8. 8.
    Dees EC, Whitfield LR, Grove WR, et al. A phase I and pharmacologic evaluation of the DNA intercalator CI-958 in patients with advanced solid tumors. Clin Cancer Res 2000;6: 3885–3894.PubMedGoogle Scholar
  9. 9.
    Babb J, Rogatko A, Zacks S. Cancer phase I clinical trials: efficient dose escalation with overdose control. Stat Med 1998;30: 1103–1120.CrossRefGoogle Scholar
  10. 10.
    Cheng JD, Babb JS, Langer C, et al. Individualized patient dosing in phase I clinical trials: the role of escalation with overdose control in PNU-214936. J Clin Oncol 2004;22:602–609.PubMedCrossRefGoogle Scholar
  11. 11.
    O'Quigley J. Another look at two phase I clinical trial designs. Stat Med 1999;18:2683–2690.PubMedCrossRefGoogle Scholar
  12. 12.
    Rinaldi DA, Burris HA, Dorr FA, et al. Initial phase I evaluation of the novel thymidylate synthase inhibitor, LY231514, using the modified continual reassessment method for dose escalation. J Clin Oncol 1995;13:2842–2850.PubMedGoogle Scholar
  13. 13.
    Gehan EA. The determination of the number of patients required in a preliminary and a follow-up trial of a new chemotherapeutic agent. J Chron Dis 1961;13:346–353.PubMedCrossRefGoogle Scholar
  14. 14.
    Fleming TR. One-sample multiple testing procedure for phase II clinical trials. Biometrics 1982;38:143–151.PubMedCrossRefGoogle Scholar
  15. 15.
    Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989;10:1–10.PubMedCrossRefGoogle Scholar
  16. 16.
    Dent S, Zee B, Dancey J, et al. Application of a new multinomial phase II stopping rule using response and early progression. J Clin Oncol 2001;19:785–791.PubMedGoogle Scholar
  17. 17.
    Green S, Weiss GR. Southwest Oncology group standard response criteria, endpoint definitions, and toxicity criteria. Invest New Drugs 1992;10:239–253.PubMedCrossRefGoogle Scholar
  18. 18.
    Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981;47:207–214.PubMedCrossRefGoogle Scholar
  19. 19.
    Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92:205–216.PubMedCrossRefGoogle Scholar
  20. 20.
    Burris HA III, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15:2403–2413.PubMedGoogle Scholar
  21. 21.
    Johnson JR, Williams G, Pazdur R. End points and United States Food and Drug Administration approval of oncology drugs. J Clin Oncol 2003;21:1404–1411.PubMedCrossRefGoogle Scholar
  22. 22.
    Patrick-Miller LJ. Is there a role for the assessment of health-related quality of life in the clinical evaluation of novel cytostatic agents? Clin Cancer Res 1990;9:1990–1994.Google Scholar
  23. 23.
    Bottomley A, Efficace F, Tjomas R, et al. Health-related quality of life in non-small-cell lung cancer: methodologic issues in randomized controlled trials. J Clin Oncol 2003;21: 2982–2992.PubMedCrossRefGoogle Scholar
  24. 24.
    Rustin GJS, Bast RC Jr., Kelloff GJ, et al. Use of CA-125 in clinical trial evaluation of new therapeutic drugs for ovarian cancer. Clin Cancer Res 2004;10:3919–3926.PubMedCrossRefGoogle Scholar
  25. 25.
    Kelloff GJ, Coffey DS, Chabner BA, et al. Prostate-specific antigen doubling time as a surrogate marker for evaluation of oncologic drugs to treat prostate cancer. Clin Cancer Res 2004;10: 3927–3933.PubMedCrossRefGoogle Scholar
  26. 26.
    Park JW, Kerbel RS, Kelloff GJ, et al. Rationale for biomarkers and surrogate end points in mechanism-driven oncology drug development. Clin Cancer Res 2004;10:3885–3896.PubMedCrossRefGoogle Scholar
  27. 27.
    Lewis JH, Kilgore ML, Goldman DP, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol 2003;21:1383–1389.PubMedCrossRefGoogle Scholar
  28. 28.
    Talarico L, Chen G, Pazdur R. Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol 2004;22:4626–4631.PubMedCrossRefGoogle Scholar
  29. 29.
    Townsley CA, Selby R, Siu LL. Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol 2005;23:3112–3124.PubMedCrossRefGoogle Scholar
  30. 30.
    Boccia R. Darbepoetin alfa in anemia management. A vital role in cancer care. Supportive Oncol 2005;3(2 Suppl. 1):3–38.Google Scholar
  31. 31.
    Dale DC. Advances in the use of colony-stimulating factors for chemotherapy-induced neutropenia. Supportive Care 2005; 3(2 Suppl. 1):39–72.Google Scholar
  32. 32.
    Stiff PJ. Oral mucositis therapy comes of age. Supportive Care 2005;3(2 Suppl. 1):73–83.Google Scholar
  33. 33.
    Trotti A, Bentzen SM. The need for adverse effects reporting standards in oncology clinical trials. J Clin Oncol 2004;22:19–22.PubMedCrossRefGoogle Scholar
  34. 34.
    Arteaga CL, Baselga J. Clinical trial design and end points for epidermal growth factor receptor-targeted therapies: implications for drug development and practice. Clin Cancer Res 2003;9:1579–1389.PubMedGoogle Scholar
  35. 35.
    Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 2005;23:1011–1027.PubMedCrossRefGoogle Scholar
  36. 36.
    Thompson JE, Thompson CB. Putting the rap on akt. J Clin Oncol 2004;22:4217–4226.PubMedCrossRefGoogle Scholar
  37. 37.
    Vande Woude GF, Kelloff GJ, Ruddon RW, et al. Reanalysis of cancer drugs: old drugs, new tricks. Clin Cancer Res 2004;10: 3897–3907.PubMedCrossRefGoogle Scholar
  38. 38.
    Tyers M, Mann M. From genomics to proteomics. Nature 2003;422:193–197.PubMedCrossRefGoogle Scholar
  39. 39.
    Mohr S, Leikauf GD, Keith G, et al. Microarrays as cancer keys: an array of possibilities. J Clin Oncol 2002;20:3165–3175.PubMedCrossRefGoogle Scholar
  40. 40.
    Giaccone G, Herbst RS, Manegold C, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small cell lung cancer: A phase III trial-INTACT 1. J Clin Oncol 2004;22: 777–784.PubMedCrossRefGoogle Scholar
  41. 41.
    Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small cell lung cancer: a phase III trial-INTACT 2. J Clin Oncol 2004;22: 785–794.PubMedCrossRefGoogle Scholar
  42. 42.
    Gatzemeier U, Pluzanska A, Szczesna A, et al. Results of a phase III trial of erlotinib HCL (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 2004;22:617 (abstract 7010).Google Scholar
  43. 43.
    Herbst RS, Prager D, Hermann R, et al. TRIBUTE- A phase III trial of erlotinib HCL (OSI-774) combined with carboplatin and paclitaxel (CP) chemotherapy in advanced non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 2004;22:617 (abstract 7011).Google Scholar

4 References

  1. 1.
    Murphy S. Regulatory framework for pediatric drug development in the US. Drug Information Association presentation, June 16, 2004.Google Scholar
  2. 2.
    Murphy D. The role of the FDA in pediatric research. Glaser Pediatrics Research Network presentation, July 16, 2004.Google Scholar
  3. 3.
    MacLeod SM. DIA Annual Meeting, June 17, 2005.Google Scholar
  4. 4.
    Pediatrics and Child Health 2003;8 Suppl. A.Google Scholar
  5. 5.
    Heinrich J. Pediatric drug research. Substantial increase in studies of drugs for children, but some challenges remain. U.S. General Accounting Office; May 8, 2001. GAO-01–705T.Google Scholar
  6. 6.
    Scheiner MS. Paediatric clinical trials redressing the imbalance. Nat Rev Drug Discov 2003;2(12):949–961.CrossRefGoogle Scholar
  7. 7.
    Korieth K. Pediatric trials come of age. In: State of the Clinical Trials Industry. Lamberti MJ (ed). Thomson CenterWatch, Boston, MA, 2004, 85–96.Google Scholar
  8. 8.
    American Academy of Pediatrics. 1995 Guidelines ofr the ethical conduct of studies to evaluate drugs in pediatric populatrions. Available at www.aap.org.
  9. 9.
    Goldkind SF. Special ethical protections for pediatric research participants. Available at www.fda.gov/oc/opt/presentations/PennnandTemple.html.
  10. 10.
    Birenbaum D. Best practices for children Act: an FDA implementation perspective presentation. FDA, March 27, 2003.Google Scholar
  11. 11.
    U.S. HHS, FDA, CDER/CBER, ICH, Guidance for Industry, E11 Clinical Investigation of Medicinal Products in the Pediatric Population, December 2000.Google Scholar
  12. 12.
    Lee P. Bridging studies in drug development (for different scenarios). Pharmaceutical Sciences World Congress presentation, June 2004.Google Scholar
  13. 13.
    Murphy S. Div. Ped. Drug Dev., CDER, FDA, Presentation DIA Annual Meeting, June 18, 2005.Google Scholar
  14. 14.
    Murphy S. Presentation NICHD Symposium, May 2005.Google Scholar

5 References

  1. 1.
    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington DC, American Psychiatric Association, 2000.CrossRefGoogle Scholar
  2. 2.
    Anonymous. National Institutes of Mental Health. The numbers count. Mental disorders in America. 2001. Available at http://www.nimh. nih.gov.
  3. 3.
    Anonymous. National Institutes on Drug Abuse. NIDA Infofacts: costs to society. 1992 data set. Available at http://www.nida.nih.gov..
  4. 4.
    McKhann G, Drachman D, Folsetin M, et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDA-ARDA work group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984; 34: 939–944.PubMedGoogle Scholar
  5. 5.
    Bowden CL, Brugger AM, Swann AC, et al. Efficacy of divalproex vs lithium and placebo in the treatment of mania. The Depakote Mania Study Group. JAMA 1994; 271: 918–924.PubMedCrossRefGoogle Scholar
  6. 6.
    Zyprexa® package insert, revised August 2004.Google Scholar
  7. 7.
    Risperdal® package insert, revised December 2003.Google Scholar
  8. 8.
    Seroquel® package insert, revised July 2004.Google Scholar
  9. 9.
    Geodon® package insert, revised August 2004.Google Scholar
  10. 10.
    Abilify® package insert, revised May 2004.Google Scholar
  11. 11.
    Lamtical® package insert, revised August 2004.Google Scholar
  12. 12.
    Tohen M, Vieta E, Calabrese J, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 2003; 60: 1079–1088.PubMedCrossRefGoogle Scholar
  13. 13.
    Guy W. ECDEU Assessment Manual for Psychopharmacology, revised 1976. US Department of Health and Human Services, Publication No. 91–338.Google Scholar
  14. 14.
    Sajatovic M, Ramirez LF. Rating Scales in Mental Health. Lexi–Comp Inc., Hudson, OH. 2001.Google Scholar
  15. 15.
    Beasley CM, Tollefson G, Tran P, et al. Olanzapine versus placebo and haloperidol. Neuropsychopharmacology 1996; 14: 111–123.PubMedCrossRefGoogle Scholar
  16. 16.
    Small JG, Hirsch SR, Arvanitis LA, et al. Quetiapine in patients with schizophrenia. Arch Gen Psychiatry 1997; 54: 549–557.PubMedGoogle Scholar
  17. 17.
    Daniel DG, Zimbroff DL, Potkin SG, et al. Ziprasidone 80 mg/day and 160 mg/day in the acute excerbation of schizophrenia and schizoaffective disorder: a 6-week and placebo-controlled trial. Neuropsychopharmacology 1999; 20: 491–505.PubMedCrossRefGoogle Scholar
  18. 18.
    Kane JM, Carson WH, Saha AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 2002; 63: 763–771.PubMedGoogle Scholar
  19. 19.
    Corey–Bloom J, Anand R, Veach, et al. A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartate), a new acetylcholinesterase inhibitor, in patients with mild to moderate severe Alzheimer's Disease. Int J Geriatr Psychopharmacol 1999; 1: 55–65.Google Scholar
  20. 20.
    Reisberg B, Doody R, Stoffler A, Schmidt F, Ferris S, Mobius HJ for the Memantine Study Group. Memantine in moderate to severe Alzheimer's Disease. N Engl J Med 2003; 348: 1333–1341.PubMedCrossRefGoogle Scholar
  21. 21.
    Kinon BJ, Ahl J, Stauffer VL, Hill AL, Buckley PF. Dose response and atypical antipsychotics in schizophrenia. CNS Drugs 2004; 18: 597–616.PubMedCrossRefGoogle Scholar
  22. 22.
    Davidson JRT, Bose A, Korotzer A, Zheng H. Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo-controlled, flexible dose study. Depression and Anxiety 2004; 19: 234–240.PubMedCrossRefGoogle Scholar
  23. 23.
    Meehan K, Zhang F, David S, et al. A double-blind, randomized comparison of the efficacy and safety of intramuscular olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania. J Clin Psychopharmacol 2001; 21: 389–397.PubMedCrossRefGoogle Scholar
  24. 24.
    Kapur S, Zipursky R, Jones C, Shammi CS, Remington G, Seeman P. A positron emission tomography study of quetiapine in schizophrenia. Arch Gen Psychiatry 2000; 57: 553–559.PubMedCrossRefGoogle Scholar
  25. 25.
    Cutler NR, Sramek JJ, Greenblatt DJ, et al. Defining the maximum tolerated dose: investigator, academic and regulatory perspectives. J Clin Pharmacol 1997; 37: 767–783.PubMedGoogle Scholar
  26. 26.
    Cutler NR, Sramek JJ. Optimizing the dose for Alzheimer's disease therapeutics: bridging and dynabridge methodologies. In. Research and Practice in Alzheimer's Disease, vol. 2. Springer, New York, 1999, p. 265–269.Google Scholar
  27. 27.
    Sramek JJ, Kirkesseli S, Paccaly-Moulin A, et al. A bridging study of fanaserin in schizophrenic patients. Psychopharmacol Bull 1998; 34: 811–818.PubMedGoogle Scholar
  28. 28.
    Sramek JJ, Anand R, Wardle TS, et al. Safety/tolerability trial of SDZ ENA 713 in patients with probable Alzheimer's disease. Life Sci 1996; 58: 1201–1207.PubMedCrossRefGoogle Scholar
  29. 29.
    Kane JM, Boyd MA, Casey DE, Jarboe KS, Keith S, McEvoy JP. Treatment of schizophrenia with long-acting injectable medications. J Clin Psychiatry 2003; 64: 1250–1257.CrossRefGoogle Scholar
  30. 30.
    Kelleher JP, Centorrino F, Albert MJ, Baldessarini RJ. Advances in atypical antipsychotics for the treatment of schizophrenia. CNS Drugs 2002; 16: 249–261.PubMedCrossRefGoogle Scholar
  31. 31.
    Norman TR, Olver JS. New formulations of existing antidepressants. CNS Drugs 2004; 18: 506–520.CrossRefGoogle Scholar
  32. 32.
    Chrisp P, Mammen GJ, Sorkin EM. Selegiline: a review of its pharmacology, symptomatic benefits and protection potential in Parkinson's Disease. Drugs Aging 1991; 1: 228–248.PubMedCrossRefGoogle Scholar
  33. 33.
    Bodkin JA, Amsterdam JD. Transdermal selegiline in major depression: a double-blind, placebo-controlled, parallel group study in outpatients. Am J Psychiatry 2002; 159: 1869–1875.PubMedCrossRefGoogle Scholar
  34. 34.
    Barrett JS, Hochadel TJ, Morales RJ, et al. Pharmacokinetics and safety of a selegiline transdermal system relative to single-dose oral administration in the elderly. Am J Ther 1996; 3: 688–698.PubMedCrossRefGoogle Scholar
  35. 35.
    Wecker L, James S, Copeland N, Pacheco MA. Transdermal selegiline: targeted effects on monoamine oxidases in the brain. Biol Psychiatry 2003; 54: 1099–1104.PubMedCrossRefGoogle Scholar
  36. 36.
    Glassman AH, Bigger JT. Antipsychotic drugs: prolonged QTc interval, Torsade de Pointes, and sudden death. Am J Psychiatry 2001; 158: 1774–1778.PubMedCrossRefGoogle Scholar
  37. 37.
    Harrigan EP, Milceli JJ, Anziano R, et al. A randomized evaluation of the effects of six antipsychotic agents on QTC, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol 2004; 24: 62–69.PubMedCrossRefGoogle Scholar
  38. 38.
    Lam YWF, Ereshefsky L, Toney GB, Gonzales C. Brand vs generic clozapine: bioavailability comparison and interchangeability study. J Clin Psychiatry 2001; 62 (suppl. 5): 18–22.PubMedGoogle Scholar
  39. 39.
    Clozapine. US Food and Drug Administration Center for Drug Evaluation and Research [online]. Available athttp:www.fda. gov.cder/infopage/clozapine/clozapine.htm.
  40. 40.
    Arranz MJ, Collier D, Kerwin RW. Pharmacogenetics for the individualization of psychiatric treatment. Am J Pharmacogenomics 2001; 1: 3–10.PubMedCrossRefGoogle Scholar
  41. 41.
    Wong ML, Licinio J. From monoamines to genomic targets: a pardigm shift for drug discovery in depression. Nature Drug Discovery 2004; 3: 135–151.Google Scholar
  42. 42.
    Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA 2000; 283: 2701–2711.PubMedCrossRefGoogle Scholar
  43. 43.
    Roberts LW, Roberts B. Psychiatric research ethics: an overview of evolving guidelines and current ethical dilemmas in the study of mental illness. Biol Psychiatry 1999; 46: 1025–1038.PubMedCrossRefGoogle Scholar
  44. 44.
    Casey DE. Clinical trial design issues in schizophrenic research. J Clin Psychiatry 2001; 62 (suppl. 9): 17–20.PubMedGoogle Scholar
  45. 45.
    Collaborative Working Group on Clinical Trials Evaluations. Clinical development of atypical antipsychotics: research design and evaluation. J Clin Psychiatry 1998; 59 (suppl. 12): 10–16.Google Scholar
  46. 46.
    Rosenstein DL. IRB review of psychiatric medication discontinuation and symptom-provoking studies. Biol Psychiatry 1999; 46: 1039–1043.PubMedCrossRefGoogle Scholar
  47. 47.
    Jeste DV, Palmer BW, Harris MJ. Neuroleptic discontinuation in clinical and research settings: scientific issues and ethical dilemmas. Biol Psychiatry 1999; 46: 1050–1059.PubMedCrossRefGoogle Scholar
  48. 48.
    Vittiello B, Jensen PS, Hoagwood K. Integrating science and ethics in child and adolescent psychiatry research. Biol Psychiatry 1999; 46: 1044–1049.CrossRefGoogle Scholar
  49. 49.
    Ernst RL, Hay JW. The US economic and social costs of Alzheimer's disease revisited. Am J Public Health 1994; 84: 1261–1264.PubMedCrossRefGoogle Scholar
  50. 50.
    Lamberti MJ. An industry in evolution, 4th ed. Thomson CenterWatch, Boston, MA, 2003, pg 43, 47.Google Scholar
  51. 51.
    Anonymous. From pipeline to market 2004. Med Ad News supplement, July 2004, pp. 35–74.Google Scholar
  52. 52.
    Ketter TA, Kalali AH, Weisler RH for the SPD417 Study Group. A 6–month multicenter, open–label evaluation of beaded extended release carbamazepine capsule monotherapy in bipolar disorder patients with manic or mixed episodes. J Clin Psychiatry 2004; 65: 668–673.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • C. Michael White
    • 1
  • Jeffrey Kluger
    • 2
  • Jessica Song
    • 3
  1. 1.School of Arrythmia & Cardiac Pharmacology & Research Group, Hartford HospUniversity of ConnecticutCT
  2. 2.Heart Rhythm ServiceUniversity of ConnecticutCT
  3. 3.Santa Clara Valley Medical CenterUniversity of PacificCA

Personalised recommendations