P.Mean >> Category >> Randomization in research (created 2007-09-12).

These pages describe the logistics and the ethical issues associated with the use of randomization to allocate patients into the treatment and control groups.Also see Category: Equipoise in research, Category: Placebos in research, Category: Observational studies, Category: Research designs.

2012

17. P.Mean: A fishy story about randomization (created 2012-05-12). I was told this story but have no way of verifying its accuracy. It is one of those stories that if it is not true, it should be. It illustrates why randomization is important. A long, long, time ago, a research group wanted to examine a pollutant to find concentration levels that would kill fish. This research required that 100 fish be separated into five tanks, each of which would get a different level of the pollutant.

2009

16. The Monthly Mean: Hide that randomization list. (January 2009)

Other resources:

Journal article: A G Randolph, D J Cook, C A Gonzales, M Andrew. Benefit of heparin in peripheral venous and arterial catheters: systematic review and meta-analysis of randomised controlled trials BMJ. 1998;316(7136):969–975. Abstract: "OBJECTIVE: To evaluate the effect of heparin on duration of catheter patency and on prevention of complications associated with use of peripheral venous and arterial catheters. DESIGN: Critical appraisal and meta-analysis of 26 randomised controlled trials that evaluated infusion of heparin intermittently or continuously. Thirteen trials of peripheral venous catheters and two of peripheral arterial catheters met criteria for inclusion. MAIN OUTCOME MEASURES: Data on the populations, interventions, outcomes, and methodological quality. RESULTS: For peripheral venous catheters locked between use flushing with 10 U/ml of heparin instead of normal saline did not reduce the incidence of catheter clotting and phlebitis or improve catheter patency. When heparin was given as a continuous infusion at 1 U/ml the risk of phlebitis decreased (relative risk 0.55; 95% confidence interval 0.39 to 0.77), the duration of patency increased, and infusion failure was reduced (0.88; 0.72 to 1.07). Heparin significantly prolonged duration of patency of radial artery catheters and decreased the risk of clot formation (0.51; 0.42 to 0.61). CONCLUSIONS: Use of intermittent heparin flushes at doses of 10 U/ml in peripheral venous catheters locked between use had no benefit over normal saline flush. Infusion of low dose heparin through a peripheral arterial catheter prolonged the duration of patency but further study is needed to establish its benefit for peripheral venous catheters." [Accessed on March 5, 2012]. http://www.ncbi.nlm.nih.gov/pubmed/9550955. Description: This article is a meta-analysis that cites three examples of alternating or haphazard assignment and excludes them from the review.

What constitutes a "clinical trial"?: A survey of oncology professionals. Description: This article summarizes ths opinions of 66 oncology researchers on what constitutes a clinical trial. While the original responses were broadly inclusive, the responses became less inclusive when definitions of the Cancer Care Ontario and the Ontario Cander Research Network groups were provided.

Adam La Caze, Benjamin Djulbegovic, Stephen Senn. What does randomisation achieve? Evidence Based Medicine. 2012;17(1):1 -2. Excerpt: "What are the benefits of random allocation in clinical studies? John Worrall, a philosopher of science, recently questioned whether evidence-based medicine's advice to base therapeutic decisions on the results of randomised controlled trials (RCTs) could be justified.1 2 Here we provide a response to Worrall and others who challenge the epistemological value of RCTs." [Accessed on January 25, 2012]. http://ebm.bmj.com/content/17/1/1.short.

Journal article: Paul Glasziou, Iain Chalmers, Michael Rawlins, Peter McCulloch. When are randomised trials unnecessary? Picking signal from noise BMJ. 2007;334(7589):349–351. Abstract: "Although randomised trials are widely accepted as the ideal way of obtaining unbiased estimates of treatment effects, some treatments have dramatic effects that are highly unlikely to reflect inadequately controlled biases. We compiled a list of historical examples of such effects and identified the features of convincing inferences about treatment effects from sources other than randomised trials. A unifying principle is the size of the treatment effect (signal) relative to the expected prognosis (noise) of the condition. A treatment effect is inferred most confidently when the signal to noise ratio is large and its timing is rapid compared with the natural course of the condition. For the examples we considered in detail the rate ratio often exceeds 10 and thus is highly unlikely to reflect bias or factors other than a treatment effect. This model may help to reduce controversy about evidence for treatments whose effects are so dramatic that randomised trials are unnecessary." [Accessed on March 5, 2012]. http://www.ncbi.nlm.nih.gov/pubmed/17303884.

Creative Commons License All of the material above this paragraph is licensed under a Creative Commons Attribution 3.0 United States License. This page was written by Steve Simon and was last modified on 2010-04-12. The material below this paragraph links to my old website, StATS. Although I wrote all of the material listed below, my ex-employer, Children's Mercy Hospital, has claimed copyright ownership of this material. The brief excerpts shown here are included under the fair use provisions of U.S. Copyright laws.

2007

15. Stats: I don't want to use a randomized trial (July 18, 2007). An email on the MedStats group outlines a new treatment that is: 1. without any significant competing treatments, 2. utilized in a heterogenous patient population, and 3. difficult to study in a randomized trial. There are a variety of alternatives to a randomized study, but I suspect that this person wants to use a historical control study. It sounds like he wants an informal endorsement from a group of professional statisticians to use a historical control study instead of a randomized study.

2006

14. Stats: Selecting randomly from a list (July 18, 2006). A common task in research is to randomly select a subgroup from a list. For example, you have the names of 26 patients, Alpha, Bravo, Charlie, Delta, etc. Suppose you want to select a small number of patients in this list, but you want to do it randomly. There are several approaches that work, but the simplest is to arrange your list in a systematic order, attach a list of random numbers and then sort your list by those random numbers. The figure below shows how this process works.

13. Stats: What is block randomization (June 30, 2006). Several people have asked me about block randomization, and while I discuss it briefly on one of my web pages, Stats: Randomization, there is a better definition on the Consort Statement web site that defines several variations of randomization including block randomization.

2005

12. Stats: An inefficient approach to randomization (August 10, 2005). Someone figured out how to prepare a randomization table on their own and it works reasonably well, but still has a few problems. She used the randbetween(1,2) function to randomly select either 1 or 2 with 50% probability. That works nicely up to a point, but at the end of the 400 rows, the total number of 1's was 223 and the total number of 2's was 177.

11. Stats: A collection of randomized and non-randomized studies (March 22, 2005). I'm updating some of my training classes to use examples from open source journals, because it is easier for me to include content of these articles directly in the web pages. An example of this is practice exercises for my training class Statistical Evidence: Apples or Oranges? But the previous practice exercise, which used a wider range of journals had some cute articles in the mix. I'll especially miss the article on episiotomy.

10. Stats: More on the weaknesses of randomized trials (February 14, 2005). I've written about the randomized trial and how it can sometimes oversimplify the research question and how it often raises difficult ethical questions. Complementary and Alternative Medicine (CAM) practices raise interesting questions about the randomized trial.

9. Stats: The ethics of randomization (January 14, 2005). A recently published article, Treatment at random: the ultimate science or the betrayal of Hippocrates? Retsas S. J Clin Oncol 2004: 22(24); 5005-8; discussion 5009-11, attacks the randomized trial and declares it to be "a deficient research tool both on deontologic and methodologic grounds."

2004

8. Stats: Is the randomized trial the gold standard for research? (September 23, 2004). I'm giving a talk next month at the Midwest Society for Pediatric Research, and here's a brief outline of what I will be saying. What I want to talk about is question that I've thought a lot about over the past few years, "What does it take to convince doctors to change their clinical practices?" Some doctors will say "I've done this way for the past thirty years and I'm not going to change now" and others will say "It was published in JAMA so it must be true". Hopefully you find yourselves somewhere between these two extremes. You don't change your practice every time a new article is published, but you do change when sufficient evidence accumulates. This is a question at the heart and soul of evidence-based medicine. When is the evidence in a journal article sufficiently compelling to cause you to change how you practice medicine?

7. Stats: Stratified randomization (August 24, 2004). A writer on the IRB Discussion Forum asked a question about how to explain stratified randomization in an informed consent document.

6. Stats: Random identification numbers (July 26, 2004). Someone asked me today for a set of random numbers. The purpose was to create an ID code that could be used to track back to the original records to resolve any inconsistencies or ambiguities. You should not use a medical record number, of course, because sharing a patients medical record number is a violation of HIPAA regulations. What you need to do is to assign a different number and then keep a link between that number and the patient's medical record number in a secure location (like a locked filing cabinet).

5. Stats: Adaptive randomization (July 15, 2004). Someone on the IRBForum posed a theoretical question. Is running a three arm study troublesome from an ethical viewpoint because the probability that any subject in the trial receives the best possible treatment decreases from 50% to 33%?

4. Stats: Criticisms of randomized clinical trials (April 7, 2004). While surfing the web, I found out about a book, Fiction and Fantasy in Medical Research. The Large-Scale Randomised Trial by James Penston (2003, The London Press, London England. ISBN: 0-9544636-1-7). The blurb on the back cover reads: "Every day, millions of patients throughout the world take treatment which is based on the results of large-scale randomised trails. But, how much do we really know about these studies? This book exposes the serious flaws in this method of medical research. Although making vast profits for the pharmaceutical  industry, large-scale randomized trials do little to improve the lives of patients and are responsible for an enormous waste of scare health care resources." Wow! That's quite an indictment.

3. Stats: Constraints on randomization (March 23, 2004). I received an inquiry from our Institutional Review Board about a study they were doing a continuing review for. This was a non-randomized comparison of two surgical techniques. The first question you might ask is: "Why didn't they randomize the treatments?" In general, it is difficult to randomize in a surgery trial.

2000

2. Stats: Alternating treatments (August 31, 2000) Dear Professor Mean, I'm running an experiment where I randomize by alternating between the treatment and the control. I was told this is not the proper way to do this. Why not?

1999

1. Stats: Randomization (August 18, 1999). Dear Professor Mean, I need to randomize the order in which I give treatments and controls in my research study, but I don't know how to randomize. Can you show me what to do? -- Baffled Beth

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