I recently finished Robert Matthew’s excellent book Chancing it: The laws of chance – and what they mean for you. One of the themes of the book is that reliance on conventional statistical methods, such as the p-value for measuring statistical significance, can lead to misleading results.
An example provided by Matthews is a UK study (known as The Grampian Region Early Anistreplase Trial, aka GREAT) from the early 1990s of clot-fighting drugs for heart attack patients, which appeared to show that administering the drugs before they reached hospital reduced the risk of death by as much as 77 percent. The range of the effect was large, but was still deemed statistically significant according to the usual definition. However subsequent studies showed that the effect of the drug was much smaller.
Pocock and Spiegelhalter (1992) had already argued that prior studies suggested a smaller effect. They used a Bayesian approach in which a prior belief is combined with the new data to arrive at a posterior result. The impact of a particular study depends not just on its apparent size, but also on factors such as the spread. Their calculations showed that the posterior distribution for the GREAT study was much closer to the (less exciting) prior than to the experimental results. The reason was that the experimental spread was large, which reduced its impact in the calculation.
Given the much-remarked low degree of reproducibility of clinical studies (in the US alone it has been estimated that approximately US$28,000,000,000 is spent on preclinical research that is not reproducible) it seems that a Bayesian approach could prove useful in many cases. To that end, we introduce the BayesianOpinionator, a web app for incorporating the effect of prior beliefs when determining the impact of a statistical study.
The data for the BayesianOpinionator app is assumed to be in the form of a comparison between two cases, denoted null and treated. For example in a clinical trial the treated case could correspond to a patient population who are treated with a particular drug, and the null case would be a comparison group that are untreated. As mentioned already, a common problem with such studies is that they produce results which appear to be statistically significant, but later turn out to be caused by a fluke. In this case the BayesianOpinionator will help to determine how seriously the results should be taken, by taking prior beiefs and data into account. The method works by representing data in terms of binomial distributions, which as seen below lead to a simple and intuitive way of applying weights to different effects in order to gauge their impact.
The New Data page is used to input the trial results, which can be in a number of different forms. The first is a binary table, with the two options denoted Pos and Neg – for example these could represent fatalities versus non-fatalities. The next is a probability distribution, where the user specifies the mean and the standard deviation of the probability p of the event taking place for each case. Finally, studies are sometimes reported as a range of the odds ratio (OR). The odds for a probability p is defined as p/1-p, so is the ratio of the chance of an event happening to the chance of it not happening. The OR is the odds of the treated case, divided by the odds of the null case. An OR of 1 represents no change, and an OR range of 0.6 to 1 would imply up to 40 percent improvement. Once the odds range is specified, the program searches for a virtual trial which gives the correct range. (The user is also asked to specify a null mean, otherwise the result is underdetermined.)
In all cases, the result is a binomial distribution for the treated and null cases, with a probability p that matches the average chance of a positive event taking place. Note that the problems studied need not be limited to binary events. For example, the data could correspond to diameter growth of a tumor with or without treatment, from a scale of 0 to 1. Alternatively, when data is input using the probability range option, a range can be chosen to scale p between any two end points, which could represent the minimum and maximum of a particular variable. In other words, while the binomial distribution is based on a sequence of binary outcomes, it generalises to continuous cases while retaining its convenient features.
In the next page Prior, the user inputs the same type of information to represent their prior beliefs about a trial. Again, this information is used to generate binomial distributions for the prior case. Finally, the two sets are pooled together in order to give the posterior result on the next page. The posterior is therefore literally the sum of the prior and the new data.
The next page, Odds, shows how the new results compare with the prior in terms of impact on the posterior. The main plot shows the log-OR distribution, which is approximately normal. A feature of the odds ratio is that it allows for a simplified representation within the Bayesian framework. The posterior distribution can be calculated as the weighted sum of the prior and the new data. The weights are given in table form, and are represented graphically by the bubble plot in the sidebar. The size of the bubbles represents spread of log-OR, while vertical position represents weight of the data, with heavy at the bottom.
As shown by Matthews (see this paper), the log-OR plot allows one to determine a critical prior interval (CPI) which can be viewed as the minimum necessary in order for the new result to be deemed statistically significant (i.e. has a 95 percent chance of excluding the possibility of no effect). If the CPI is more extreme than the result, this implies that the posterior result will not be significant unless one already considers the CPI to be realistic. For clinical trials, which for ethical reasons assume no clear advantage between the null and treated cases, the CPI acts as a reality check on new results, because if the results are very striking it shows how flexible the prior needs to be in order to see them as meaningful.
The BayesianOpinionator Shiny app can be accessed here.