Diferencias entre las características basales de los pacientes en los ensayos clínicos, según el tamaño de la muestra. Un estudio metaepidemiológico

Contenido principal del artículo

Daniel Vanegas Isaza
Mateo Zuluaga Gómez
Jorge Hernando Donado Gómez

Resumen

Objetivo: determinar las diferencias en las variables cualitativas y cuantitativas de las características basales de los ensayos clínicos controlados con asignación aleatoria, según su tamaño de muestra.


Metodología: estudio observacional, transversal que incluyó los ensayos clínicos con asignación aleatoria publicados en cuatro revistas médicas generales de alto factor de impacto. Según su tamaño de muestra, se dividieron en cinco estratos y se evaluó la diferencia entre variables cualitativas y cuantitativas de las características basales.


Resultados: se analizaron 1000 variables de los pacientes que participaron en ensayos clínicos. Cuando se comparó cada uno de los grupos por tamaño de muestra con respecto al de ≥5000 pacientes, se encontró que las diferencias de medias disminuían a medida que los tamaños de muestra tenían mayor número de pacientes.


Conclusiones: la diferencia de resultados de las características basales de los ensayos clínicos, es inversamente proporcional al tamaño de muestra y, por encima de 500 pacientes por grupo, las diferencias promedio serían menores al 1.2%.

Palabras clave:
ensayo clínico tamaño de la muestra distribución aleatoria

Citas

Groenwold RH, Donders AR, Van der Heijden GJ, Hoes AW, Rovers MM. Confounding of subgroup analyses in randomized data. Arch Intern Med. 2009;169(16):1532–4.

Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. J Clin Epidemiol. 2010;63(8):834–40.

Friedman LM, Furberg C, DeMets DL. Baseline assessment. In: Friedman LM, Furberg C, DeMets DL. Fundamentals of clinical trials.

ed. New York, NY : Springer; 2010. p. 169. 4. La Caze A, Djulbegovic B, Senn S. What does randomisation achieve? Evid Based Med. 2012;17(1):1–2.

Schulz KF, Grimes DA. Generation of allocation sequences in randomised trials: chance, not choice. Lancet. 2002;359(9305):515–9.

Pertegas SP. Investigación: la distribución normal 1/12. Cad Aten Primaria. 2001;8:268–74.

Costa ML, Achten J, Parsons NR, Edlin RP, Foguet P, Prakash U, et al. Total hip arthroplasty versus resurfacing arthroplasty in the treatment of patients with arthritis of the hip joint: single centre, parallel group, assessor blinded, randomised controlled trial. BMJ. 2012;344:e2147–e2147.

Davies HE, Mishra EK, Kahan BC, Wrightson JM, Stanton AE, Guhan A, et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383–9.

Euvrard S, Morelon E, Rostaing L, Goffin E, Brocard A, Tromme I, et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med. 2012;367(4):329–39.

Kang DH, Kim YJ, Kim SH, Sun BJ, Kim DH, Yun SC, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466–73.

Mills KL, Teesson M, Back SE, Brady KT, Baker AL, Hopwood S, et al. Integrated exposure-based therapy for co-occurring posttraumatic stress disorder and substance dependence: a randomized controlled trial. JAMA. 2012;308(7):690–9.

Paton NI, Goodall RL, Dunn DT, Franzen S, Collaco-Moraes Y, Gazzard BG, et al. Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial. JAMA. 2012;308(4):353–61.

Traverse JH, Henry TD, Ellis SG, Pepine CJ, Willerson JT, Zhao DX, et al. Effect of intracoronary delivery of autologous bone marrow mononuclear cells 2 to 3 weeks following acute myocardial infarction on left ventricular function: the LateTIME randomized trial. JAMA. 2011;306(19):2110–9.

Wong C, Jayaram L, Karalus N, Eaton T, Tong C, Hockey H, et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):660–7.

Afdhal NH, Giannini EG, Tayyab G, Mohsin A, Lee JW, Andriulli A, et al. Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. N Engl J Med. 2012;367(8):716–24.

Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre M, Martínez-Alonso M, Carmona C, Barceló A, et al. Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial. JAMA. 2012;307(20):2161–8.

Bhatnagar S, Wadhwa N, Aneja S, Lodha R, Kabra SK, Natchu UC, et al. Zinc as adjunct treatment in infants aged between 7 and 120 days with probable serious bacterial infection: a randomised, double-blind, placebo-controlled trial. Lancet. 2012;379(9831):2072–8.

Brunkhorst FM, Oppert M, Marx G, Bloos F, Ludewig K, Putensen C, et al. Effect of empirical treatment with moxifloxacin and meropenem vs meropenem on sepsis-related organ dysfunction in patients with severe sepsis: a randomized trial. JAMA. 2012;307(22):2390–9.

Cima RF, Maes IH, Joore MA, Scheyen DJ, El Refaie A, Baguley DM, et al. Specialised treatment based on cognitive behaviour therapy versus usual care for tinnitus: a randomised controlled trial. Lancet. 2012;379(9830):1951–9. 20.

Rosenfeld M, Ratjen F, Brumback L, Daniel S, Rowbotham R, McNamara S, et al. Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial. JAMA. 2012;307(21):2269–77.

Selker HP, Beshansky JR, Sheehan PR, Massaro JM, Griffith JL, D’Agostino RB, et al. Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial. JAMA. 2012;307(18):1925–33.

Van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379(9829):1879–86.

Vernooij JW, Kaasjager HA, Van der Graaf Y, Wierdsma J, Grandjean HMH, Hovens MM, et al. Internet based vascular risk factor management for patients with clinically manifest vascular disease: randomised controlled trial. BMJ. 2012:e3750–e3750.

Walsh JM, McGowan CA, Mahony R, Foley ME, McAuliffe FM. Low glycaemic index diet in pregnancy to prevent macrosomia (ROLO study): randomised control trial. BMJ. 2012;345(aug301):e5605–e5605.

Zinkstok SM, Roos YB. Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet. 2012;380(9843):731–7.

Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JAD, Criner GJ, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365(8):689–98.

Boonen S, Reginster JY, Kaufman JM, Lippuner K, Zanchetta J, Langdahl B, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med. 2012;367(18):1714–23.

Cannon CP, Shah S, Dansky HM, Davidson M, Brinton EA, Gotto AM, et al. Safety of anacetrapib in patients with or at high risk for coronary heart disease. N Engl J Med. 2010;363(25):2406–15.

Comi G, Jeffery D, Kappos L, Montalban X, Boyko A, Rocca MA, et al. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med. 2012;366(11):1000–9.

Coovadia HM, Brown ER, Fowler MG, Chipato T, Moodley D, Manji K, et al. Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, doubleblind, placebo-controlled trial. Lancet. 2012;379(9812):221–8.

De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, et al. Fractional flow reserveguided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367(11):991– 1001.

Farkouh ME, Domanski M, Sleeper LA, Siami FS, Dangas G, Mack M, et al. Strategies for Multivessel Revascularization in Patients with Diabetes. N Engl J Med. 2012; 367(25):2375-84.

Kastrati A, Neumann FJ, Schulz S, Massberg S, Byrne RA, Ferenc M, et al. Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med. 2011;365(21):1980–9.

Lienhardt C, Cook SV, Burgos M, Yorke-Edwards V, Rigouts L, Anyo G, et al. Efficacy and safety of a 4-drug fixed-dose combination regimen compared with separate drugs for treatment of pulmonary tuberculosis: the Study C randomized controlled trial. JAMA. 2011;305(14):1415–23.

Mozaffarian D. Fish Oil and postoperative fish oil and postoperative atrial fibrillation: the omega-3 fatty acids for prevention of post-operative atrial fibrillation (OPERA) randomized trial. JAMA. 2012; 308(19):2001-11.

Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011;365(22):2078–87.

Parving HH, Brenner BM, McMurray JJ, De Zeeuw D, Haffner SM, Solomon SD, et al. Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes. N Engl J Med. 2012; 367(23):2204-13

Räber L, Kelbæk H, Ostojic M, Ostoijc M, Baumbach A, Heg D, et al. Effect of biolimus-eluting stents with biodegradable polymer vs bare-metal stents on cardiovascular events among patients with acute myocardial infarction: the COMFORTABLE AMI randomized trial. JAMA. 2012;308(8):777–87.

Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, et al. Denosumab and bonemetastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2012;379(9810):39–46.

Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S, et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med. 2010;363(25):2385–95.

Benavente OR, Hart RG, McClure LA, Szychowski JM, Coffey CS, Pearce LA. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med. 2012;367(9):817–25.

TEINSTEIN–PE Investigators, Büller HR, Prins MH, Lensin AW, Decousus H,Jacobson BF, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012;366(14):1287–97.

Dávalos A, Alvarez-Sabín J, Castillo J, Díez-Tejedor E, Ferro J, Martínez-Vila E, et al. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebocontrolled study (ICTUS trial). Lancet. 2012;380(9839):349–57.

Isanaka S, Mugusi F, Hawkins C, Spiegelman D, Okuma J, Aboud S, et al. Effect of high-dose vs standard-dose multivitamin supplementation at the initiation of HAART on HIV disease progression and mortality in Tanzania: a randomized controlled trial. JAMA. 2012;308(15):1535– 44.

Manaseki-Holland S, Maroof Z, Bruce J, Mughal MZ, Masher MI, Bhutta ZA, et al. Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial. Lancet. 2012;379(9824):1419–27.

Newman MF, Ferguson TB, White JA, Ambrosio G, Koglin J, Nussmeier NA, et al. Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial. JAMA. 2012;308(2):157–64.

Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, Murray G, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet. 2012;379(9834):2352–63.

Thiele H, Wöhrle J, Hambrecht R, Rittger H, Birkemeyer R, Lauer B, et al. Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial. Lancet. 2012;379(9819):923–31.

Walden M, Atroshi I, Magnusson H, Wagner P, Hagglund M. Prevention of acute knee injuries in adolescent female football players: cluster randomised controlled trial. BMJ. 2012;344(may031):e3042–e3042.

Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, Maggioni AP, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367(4):319–28.

Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364(9):818–28.

Granger CB, Alexander JH, McMurray JJ , Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92.

Jamerson K, Weber MA, Bakris GL, Dahlöf B, Pitt B, Shi V, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23):2417–28.

Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91.

Roberts JM, Myatt L, Spong CY, Thom EA, Hauth JC, Leveno KJ, et al. Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med. 2010;362(14):1282–91.

Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome. N Engl J Med. 2012; N Engl J Med. 2012; 367(22):2089-99

Sesso HD, Christen WG, Bubes V, Smith JP, Macfadyen J, Schvartz M, et al. Multivitamins in the Prevention of Cardiovascular Disease in Men: The Physicians’ Health Study II Randomized Controlled Trial. JAMA. 2012;308(17):1751–60.

Tricoci P, Huang Z, Held C, Moliterno DJ, Armstrong PW, Van de Werf F, et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012;366(1):20–33.

FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent highgrade cervical lesions. N Engl J Med. 2007;356(19):1915–27.

Altman DG, Doré CJ. Randomisation and baseline comparisons in clinical trials. Lancet. 1990 Jan 20;335(8682):149–53.

Delgado-Rodríguez M, Llorca J. Bias. J Epidemiol Community Health. 2004;58(8):635–41.

Altman DG, Bland JM. Generalisation and extrapolation. BMJ. 1998;317(7155):409–10.

Rothwell PM. External validity of randomised controlled trials: “to whom do the results of this trial apply?”. Lancet. 2005;365(9453):82–93.

McAlister FA, Straus SE, Guyatt GH, Haynes RB. Users’ guides to the medical literature: XX. Integrating research evidence with the care of the individual patient. Evidence-Based Medicine Working Group. JAMA. 2000;283(21):2829–36.

Daniel WW. Bioestadística: base para el análisis de las ciencias de la salud. México: Limusa Wiley; 2006.

Detalles del artículo

Biografía del autor/a

Daniel Vanegas Isaza, Universidad Pontificia Bolivariana

Estudiante de Medicina, Facultad de Medicina, Universidad Pontificia Bolivariana. Medellín, Colombia.

Mateo Zuluaga Gómez, Universidad Pontificia Bolivariana

Estudiante de Medicina, Facultad de Medicina, Universidad Pontificia Bolivariana. Medellín, Colombia.

Jorge Hernando Donado Gómez, Universidad Pontificia Bolivariana

Médico internista y epidemiólogo, Hospital Pablo Tobón Uribe. Profesor, Universidad Pontificia Bolivariana. Medellín, Colombia

Artículos más leídos del mismo autor/a

<< < 1 2 3 > >>