Timothy Ingall

Mayo Clinic - Scottsdale, Scottsdale, Arizona, United States

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Publications (4)14.52 Total impact

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    ABSTRACT: Treatment group imbalances in baseline stroke severity in the NINDS intravenous t-PA for acute stroke treatment trial led to controversy regarding the efficacy of tissue plasminogen activator (t-PA) in the treatment of acute ischemic stroke. Describe the steps used to independently re-evaluate this trial. NIH appointed an independent multidisciplinary committee that gained access to the original data. We undertook analyses of t-PA efficacy accounting for this imbalance, as well as analyses to identify subgroups that experienced additional harm or benefit from t-PA. Analyses of time from stroke onset to treatment (OTT), blood pressure, and intracerebral hemorrhage are given as illustrations. Despite subgroup imbalances in baseline stroke severity, when t-PA was administered to acute ischemic stroke patients according to study protocol, there was a statistically significant and clinically important benefit of t-PA treatment resulting in a higher likelihood of having a favorable clinical outcome at 3 months. Moreover, we were unable to identify subgroups of patients between which t-PA treatment effect differed, albeit these analyses had low power. These data failed to support the NINDS investigators' conclusion that effect of t-PA therapy diminished with increasing values of OTT within the protocol-specified 3 h time limit. In addition, the blood pressure measurements were highly variable and inconsistently determined so as to be too unreliable for inclusion in analysis. With new NIH requirements for data-sharing, the frequency of re-analysis of clinical trial data may increase substantially. This re-evaluation provides a blueprint for future re-evaluations of other trials. These best practices include re-analysis of the study data, after suitable replication, by an independent multidisciplinary committee, including a skilled statistical programmer analyst. Primary investigators should address significant errors determined in such re-analyses.
    Clinical Trials 02/2008; 5(4):308-15. · 2.20 Impact Factor
  • Stroke 01/2005; 36(3):529-530. · 6.16 Impact Factor
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    ABSTRACT: Following publication of concerns about the results of the National Institute of Neurological Disorders and Stroke (NINDS) intravenous tissue plasminogen activator (t-PA) in acute stroke treatment trial, NINDS commissioned an independent committee "to address whether there is concern that eligible stroke patients may not benefit from t-PA given according to the protocol used in the trials and, whether the subgroup imbalance (in baseline stroke severity) invalidates the entire trial." The original NINDS trial data were reanalyzed to assess the t-PA treatment effect, the effect of the baseline imbalance in stroke severity between the treatment groups on the t-PA treatment effect, and whether subgroups of patients did not benefit from receiving t-PA. A clinically important and statistically significant benefit of t-PA therapy was identified despite subgroup imbalances in baseline stroke severity and an increased incidence of symptomatic intracerebral hemorrhage in t-PA treated patients. The adjusted t-PA to placebo odds ratio (OR) of a favorable outcome was 2.1 (95% CI, 1.5 to 2.9). Although these exploratory analyses found no statistical evidence that the t-PA treatment effect differed among patient subgroups, the study was not powered to detect subgroup treatment differences. These findings support the use of t-PA to treat patients with acute ischemic stroke within 3 hours of onset under the NINDS t-PA trial protocol. Health professionals should work collaboratively to develop guidelines to ensure appropriate use of t-PA in acute ischemic stroke patients.
    Stroke 11/2004; 35(10):2418-24. · 6.16 Impact Factor
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    Timothy Ingall
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    ABSTRACT: In the United States, 700,000 strokes, responsible for 165,000 deaths, occur each year. Worldwide, stroke is the 2nd leading cause of death. Stroke is a major health problem; and as the population ages, its significance will grow. This paper reviews the epidemiology of stroke, the identification of modifiable risk factors, and some of the options for intervention that can reduce stroke-related mortality and morbidity. Though the diagnosis and care of stroke patients has improved, mortality resultant from stroke remains significant, with only 50% 5-year survival in some clinical studies. The risk of stroke following a transient ischemic attack (TIA) or initial stroke is also significant-approximately 30% following either event. Stroke severity at onset and patient age are the most important factors for predicting prognosis. Stroke prevention focuses on management of the traditional cardiovascular risk factors especially control of blood pressure and smoking cessation. The role of diabetes and lipid control in stroke prevention continues to be studied. The optimum use of anticoagulation to reduce stroke risk has been explored by the Stroke in Patients with Atrial Fibrillation (SPAF) studies. Carotid endarterectomy is effective in stroke prevention for those with symptomatic carotid obstruction of 70%, but its role in other scenarios is less certain. Antiplatelet drugs continue to be an important therapy for the prevention of recurrent stroke. Centralized stroke centers that specialize in stroke diagnosis and care along with rapidly rendering appropriate treatment can improve mortality and morbidity of stroke by 20%.
    Journal of insurance medicine (New York, N.Y.) 02/2004; 36(2):143-52.

Publication Stats

174 Citations
14.52 Total Impact Points

Institutions

  • 2004
    • Mayo Clinic - Scottsdale
      Scottsdale, Arizona, United States
    • Mayo Foundation for Medical Education and Research
      • Department of Neurology
      Scottsdale, AZ, United States