Exploratory thoughts on clinical trials with utilities

We consider problems of choice of sample size and allocation in the clinical trials context when utilities are explicitly taken into account. In particular, we consider utilities of benefits and side-effects (and their trade-offs), as well as utility functions that trade-off scientific and ethical concerns.     

A case for Bayesianism in clinical trials

This paper describes a Bayesian approach to the design and analysis of clinical trials, and compares it with the frequentist approach. Both approaches address learning under uncertainty. But they are different in a variety of ways. The Bayesian approach is more flexible. For example, accumulating data from a clinical trial can be used to update Bayesian measures, independent of the design of the trial. Frequentist measures are tied to the design, and interim analyses must be planned for frequentist measures to have meaning. Its flexibility makes the Bayesian approach ideal for analysing data from clinical trials. In carrying out a Bayesian analysis for inferring treatment effect, information from the clinical trial and other sources can be combined and used explicitly in drawing conclusions. Bayesians and frequentists address making decisions very differently. For example, when choosing or modifying the design of a clinical trial, Bayesians use all available information, including that which comes from the trial itself. The ability to calculate predictive probabilities for future observations is a distinct advantage of the Bayesian approach to designing clinical trials and other decisions. An important difference between Bayesian and frequentist thinking is the role of randomization.     

A multiple decision procedure in clinical trials

In some multiple treatment arm clinical trials there is an order of preference for the treatments based on secondary considerations like toxicity or cost. In this paper, we consider the case where two or more treatments could have equal prior preference. This formulation includes the problem of comparing several equally preferred experimental treatments to one control, or the comparison of a combination with its components. Our decision procedures will guarantee a high selection probability for the correct treatment(s) when that selection is appropriate. We establish sample size requirements for our decision procedures which can be applied to clinical trials with normal, binomial, or right censored exponential endpoints.     

Self-designing clinical trials

I present a method of sequential analysis for randomized clinical trials that allows use of all prior data in a trial to determine the use and weighting of subsequent observations. One continues to assign subjects until one has 'used up' all the variance of the test statistic. There are many strategies to determine the weights including Bayesian methods (though the proposal is a frequentist design). I explore further the self-designing aspect of the randomized trial to note that in some cases it makes good sense (i) to change the weighting on components of a multivariate endpoint, (ii) to add or drop treatment arms (especially in a parallel group dose ranging/efficacy/safety trial), (iii) to select sites to use as the trial goes on, (iv) to change the test statistic and (v) even to rethink the whole drug development paradigm to shorten drug development time while keeping current standards for the level of evidence necessary for approval.     

A clinical note on traumatic experiences and the patient's anger.

When an analyst is working with a patient who has had traumatic experiences, the analyst might be inclined to try too soon to make the patient aware of his or her rage about the experiences. However, premature activation of anger about the traumatizing relationship, either by the analyst or by the patient, may endanger or end the therapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A note on the training of clinical and counseling psychologists.

"In June of 1958, letters were sent to the department chairmen of the 24 institutions approved by the APA Education and Training Board to train PhD psychologists in both the clinical and counseling specialties… . One-third of the 24 institutions are known to differentiate definitely in course requirements between the two specialties, while only one-eight are known to differentiate definitely in the preliminary examinations used for the two specialties… . Only three of the institutions definitely differentiate between the specialties in terms of both course requirements and preliminary examinations… . it seems obvious that little differentiation is being made between the two specialties in our major training institutions even though these institutions are approved to train for each of the specialties." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Therapy and clinical trials

Little is know about intraosseous migration of nonerupting teeth, a rare natural condition of horizontal tooth movement and impaction. It occurs only in the mandible and involves primarily the second premolar or the canine. When the second premolar is the affected tooth, it always is found distal to its normal position. The origins of the second premolar intraosseous migration phenomenon are obscure and usually no treatment is recommended. Intraosseous migration involving the canine is commonly called transmigration because the affected canine moves mesially across the mandibular symphysis to the opposite side of the mandible. Analysis of 50 published cases of canine transmigration indicated higher occurrence in women and no sidedness preference. In over 80% of the studied cases, the canine remained nonerupted and, of the 24 cases receiving some treatment, all but two underwent extraction of the anomalous canine. The canine transmigration phenomenon appears to show signs of having some genetic determinants.     

A flexible random allocation program for multi-institutional clinical trials

This paper describes a flexible random allocation program that assigns treatments to patients according to their prognostic factors in multi-institutional clinical trials. The source lists are available in the appendix of this paper. This program is based on Pocock and Simon's minimization method and Zelen's method for institution balancing. The numbers of institutions, treatments, and prognostic factors can be set arbitrarily. The maximum number of institutions, treatments, or prognostic factors that can be accommodated by the program is limited only by the size of the main memory. For example, an IBM-PC with a 640KB main memory can run a program of 1500 institutions, 4 treatments and 20 prognostic factors.     

Using WAIS—R short forms with clinical outpatients: A cautionary note.

To evaluate the validity of Wechsler Adult Intelligence Scale-Revised (WAIS-R) short forms with clinical outpatients, the test protocols of 90 people seen at a university-based psychology clinic were rescored for 1 selected-items and 10 selected-subtest combinations. Three criteria (high correlations, nonsignificant t tests, and limited percentage of classification changes), which have frequently been used in previous short-form studies, were used to evaluate the validity of the 11 WAIS-R short forms. None of the short forms was found satisfactorily to meet the three criteria. Cautions about using the evaluated short forms with clinical outpatients were provided. (PsycINFO Database Record (c) 2010 APA, all rights reserved)