Perils of Evidence-Based Medicine

Evidenced-based medicine views random-assignment clinical trials as the gold standard of evidence. Because patient populations are heterogeneous, large numbers of patients must be studied in order to achieve statistically significant results, but the means or medians of these large samples have weak predictive validity for individual patients. Further, the logic of random-assignment clinical trials allows only the inference that some subset of patients benefits from the treatment. Post-hoc analysis is therefore necessary to identify those patients. Otherwise, many patients may receive treatments that are useless and potentially harmful.

[1]  W. W. Rozeboom The fallacy of the null-hypothesis significance test. , 1960, Psychological bulletin.

[2]  D. Bakan,et al.  The test of significance in psychological research. , 1966, Psychological bulletin.

[3]  D. Bamber The area above the ordinal dominance graph and the area below the receiver operating characteristic graph , 1975 .

[4]  R. Kronmal,et al.  Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators. , 1992, Journal of the American College of Cardiology.

[5]  D. Nelson,et al.  Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. , 1993, Journal of the National Cancer Institute.

[6]  W. Curran,et al.  Validation and predictive power of Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90-06. , 1998, International journal of radiation oncology, biology, physics.

[7]  M J Gleason,et al.  Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  L. Zamorano,et al.  Use of the RTOG recursive partitioning analysis to validate the benefit of iodine-125 implants in the primary treatment of malignant gliomas. , 1999, International journal of radiation oncology, biology, physics.

[9]  D. Osoba,et al.  A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse , 2000, British Journal of Cancer.

[10]  M. Chamberlain,et al.  Medical Research Council adjuvant trial in high-grade gliomas. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  M. member Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a medical research council trial. , 2001 .

[12]  David M. Thomas,et al.  Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  J. Olson,et al.  The Brain Tumor Cooperative Group NIH Trial 87-01: a randomized comparison of surgery, external radiotherapy, and carmustine versus surgery, interstitial radiotherapy boost, external radiation therapy, and carmustine. , 2002, Neurosurgery.

[14]  The Use of Frailty Hazard Models for Unrecognized Heterogeneity That Interacts with Treatment: Considerations of Efficiency and Power , 2002, Biometrics.

[15]  J. Karlawish,et al.  The continuing unethical conduct of underpowered clinical trials. , 2002, JAMA.

[16]  M. Prados,et al.  Phase III randomized study of radiotherapy plus procarbazine, lomustine, and vincristine with or without BUdR for treatment of anaplastic astrocytoma: final report of RTOG 9404. , 2004, International journal of radiation oncology, biology, physics.

[17]  Robyn Bluhm,et al.  From Hierarchy to Network: a richer view of evidence for evidence-based medicine , 2005, Perspectives in biology and medicine.

[18]  R. Mirimanoff,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[19]  P. Killeen,et al.  An Alternative to Null-Hypothesis Significance Tests , 2005, Psychological science.

[20]  J. Grossman,et al.  The Randomized Controlled Trial: gold standard, or merely standard? , 2005, Perspectives in biology and medicine.

[21]  R. Mirimanoff,et al.  MGMT gene silencing and benefit from temozolomide in glioblastoma. , 2005, The New England journal of medicine.

[22]  P. Loehrer Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma , 2006 .

[23]  Denis Lacombe,et al.  Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Walter Curran,et al.  Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  A. Fortin,et al.  Antioxidant vitamins supplementation and mortality: A randomized trial in head and neck cancer patients , 2006, International journal of cancer.

[26]  S. Mouly,et al.  Antiarrhythmic drugs for maintaining sinus rhythm after cardioversion of atrial fibrillation: a systematic review of randomized controlled trials. , 2006, Archives of internal medicine.

[27]  Nancy Cartwright,et al.  Are RCTs the Gold Standard? , 2007 .

[28]  A. Fortin,et al.  Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long‐term effects on recurrence and mortality: A randomized trial among head and neck cancer patients , 2007, International journal of cancer.

[29]  B. Scheithauer,et al.  Cognition and quality of life after chemotherapy plus radiotherapy (RT) vs. RT for pure and mixed anaplastic oligodendrogliomas: Radiation therapy oncology group trial 9402. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  Maya J Goldenberg,et al.  Iconoclast or Creed?: Objectivism, Pragmatism, and the Hierarchy of Evidence , 2009, Perspectives in biology and medicine.

[31]  Kirstin Borgerson,et al.  Valuing Evidence: Bias and the Evidence Hierarchy of Evidence-Based Medicine , 2009, Perspectives in biology and medicine.

[32]  B. Theeler,et al.  High-Grade Gliomas , 2011, Current treatment options in neurology.

[33]  D. Petrač Antiarrhythmic drugs for maintaining of sinus rhythm , 2011 .