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CC BY-NC-ND 4.0 · Avicenna J Med 2020; 10(02): 68-75
DOI: 10.4103/ajm.ajm_186_19
Original Article

How to read a published clinical trial: a practical guide for clinicians

Mohamad B Sonbol
Mayo Clinic Cancer Center, Phoenix, Arizona
,
Belal M Firwana
Heartland Cancer Research, National Cancer Institute Community Oncology Research Program (NCORP), Missouri Baptist Medical Center, St. Louis, Missouri
,
Talal Hilal
University of Mississippi Medical Center, Jackson, Mississippi
,
Mohammad Hassan Murad
Evidence-Based Practice Center, Mayo Clinic, Rochester, Minnesota, USA
› Author Affiliations
Subject Editor: Financial support and sponsorship Nil.
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Abstract

Over the last 5 years, there have been more than 140 new drug approvals in the field of Oncology alone, all based on newly published clinical trials. These approvals have led to an ongoing change in clinical practice, offering new therapeutic options for patients. Therefore, it is important for healthcare providers to be able to appraise a clinical trial and determine its validity, understand its results, and be able to apply such results to their patients. In this guide, we provide a simplified approach tailored to practicing clinicians and trainees. The same concepts and principles apply to other medical specialties.

Keywords

Apixaban - apixaban for the prevention of venous thromboembolism - critical appraisal - evidence-based medicine - evidence-based practice - randomized-clinical trials


Publication History

Article published online:
04 August 2021

© 2020. Syrian American Medical Society. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Hilal T, Sonbol MB, Prasad V. Analysis of control arm quality in randomized clinical trials leading to anticancer drug approval by the US food and drug administration. JAMA Oncol 2019; 5: 887-92
    CrossrefPubMedGoogle Scholar
  • 2 Guyatt G, Rennie D, Meade MO, Cook DJ. Users’ Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. 3rd ed. New York: McGraw-Hill;
    Google Scholar
  • 3 Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111: 4902-7
    CrossrefPubMedGoogle Scholar
  • 4 Murad MH, Asi N, Alsawas M, Alahdab F. New evidence pyramid. Evid Based Med 2016; 21: 125-7
    CrossrefPubMedGoogle Scholar
  • 5 Akobeng AK. Principles of evidence based medicine. Arch Dis Child 2005; 90: 837-40
    CrossrefPubMedGoogle Scholar
  • 6 Prasad K. Fundamentals of Evidence Based Medicine. India: Springer; 2014
    CrossrefGoogle Scholar
  • 7 Carrier M, Abou-Nassar K, Mallick R, Tagalakis V, Shivakumar S, Schattner A. et al AVERT Investigators. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2019; 380: 711-9
    CrossrefPubMedGoogle Scholar
  • 8 Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. USA: The Cochrane Collaboration; 2011
    Google Scholar
  • 9 Jüni P, Altman DG, Egger M. Systematic reviews in health care: Assessing the quality of controlled clinical trials. BMJ 2001; 323: 42-6
    CrossrefPubMedGoogle Scholar
  • 10 Schulz KF, Chalmers I, Altman DG. The landscape and lexicon of blinding in randomized trials. Ann Intern Med 2002; 136: 254-9
    CrossrefPubMedGoogle Scholar
  • 11 Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995; 273: 408-12
    CrossrefPubMedGoogle Scholar
  • 12 Schulz KF, Grimes DA. Generation of allocation sequences in randomised trials: Chance, not choice. Lancet 2002; 359: 515-9
    CrossrefPubMedGoogle Scholar
  • 13 Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D. et al BILCAP study group. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): A randomised, controlled, multicentre, phase 3 study. Lancet Oncol 2019; 20: 663-73
    CrossrefPubMedGoogle Scholar
  • 14 Karanicolas PJ, Farrokhyar F, Bhandari M. Practical tips for surgical research: Blinding: Who, what, when, why, how?. Can J Surg 2010; 53: 345-8
    PubMedGoogle Scholar
  • 15 Hróbjartsson A, Emanuelsson F, Skou Thomsen AS, Hilden J, Brorson S. Bias due to lack of patient blinding in clinical trials. A systematic review of trials randomizing patients to blind and nonblind sub-studies. Int J Epidemiol 2014; 43: 1272-83
    CrossrefPubMedGoogle Scholar
  • 16 Nüesch E, Reichenbach S, Trelle S, Rutjes AW, Liewald K, Sterchi R. et al. The importance of allocation concealment and patient blinding in osteoarthritis trials: A meta-epidemiologic study. Arthritis Rheum 2009; 61: 1633-41
    CrossrefPubMedGoogle Scholar
  • 17 Meng Z, Garcia MK, Hu C, Chiang J, Chambers M, Rosenthal DI. et al. Randomized controlled trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma. Cancer 2012; 118: 3337-44
    CrossrefPubMedGoogle Scholar
  • 18 Madsen MV, Gøtzsche PC, Hróbjartsson A. Acupuncture treatment for pain: Systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups. BMJ 2009; 338: a3115
    CrossrefPubMedGoogle Scholar
  • 19 Devereaux PJ, Bhandari M, Montori VM, Manns BJ, Ghali WA, Guyatt GH. Double blind, you are the weakest link––good-bye!. ACP J Club 2002; 136: A11
    CrossrefPubMedGoogle Scholar
  • 20 Greer JA, Amoyal N, Nisotel L, Fishbein JN, MacDonald J, Stagl J. et al. A systematic review of adherence to oral antineoplastic therapies. Oncologist 2016; 21: 354-76
    CrossrefPubMedGoogle Scholar
  • 21 Higgins JPT, Sterne JAC, Savović J, Page MJ, Hróbjartsson A, Boutron I. et al. A revised tool for assessing risk of bias in randomized trials. Cochrane Methods. Cochrane Database Syst Rev 2016; 10: 29-31
    Google Scholar
  • 22 Abraha I, Montedori A. Modified intention to treat reporting in randomised controlled trials: Systematic review. BMJ 2010; 340: c2697
    CrossrefPubMedGoogle Scholar
  • 23 Beckett RD, Loeser KC, Bowman KR, Towne TG. Intention-to-treat and transparency of related practices in randomized, controlled trials of anti-infectives. BMC Med Res Methodol 2016; 16: 106
    CrossrefPubMedGoogle Scholar
  • 24 Page MJ, Higgins JP, Clayton G, Sterne JA, Hróbjartsson A, Savović J. Empirical evidence of study design biases in randomized trials: Systematic review of meta-epidemiological studies. PLoS One 2016; 11: e0159267
    CrossrefPubMedGoogle Scholar
  • 25 Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F. et al KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 2018; 378: 2078-92
    CrossrefPubMedGoogle Scholar
  • 26 Murad MH, Montori VM, Walter SD, Guyatt GH. Estimating risk difference from relative association measures in meta-analysis can infrequently pose interpretational challenges. J Clin Epidemiol 2009; 62: 865-7
    CrossrefPubMedGoogle Scholar
  • 27 Alahdab F, Haydour Q, Murad MH. Teaching tips: Explaining hazard ratios. In: Newsletter of the International Society for Evidence-Based Health Care. Busse Jason, Glasziou Paul, Guyatt Gordon. editors 13. 2013
    Google Scholar
  • 28 Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S. et al National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A phase III trial of the national cancer institute of Canada clinical trials group. J Clin Oncol 2007; 25: 1960-6
    CrossrefPubMedGoogle Scholar
  • 29 Murad MH, Katabi A, Benkhadra R, Montori VM. External validity, generalisability, applicability and directness: A brief primer. BMJ Evid Based Med 2018; 23: 17-9
    CrossrefPubMedGoogle Scholar
  • 30 Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A. et al ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 2007; 357: 1810-20
    CrossrefPubMedGoogle Scholar