Concurrent treatments

Studying the effects of two treatments together is important because combinations are often found to be useful in clinical practice with synergism of effect and reduced side effects. Traditionally, different combinations of two drugs can be assessed and the results represented graphically as an isobologram79 - an example is given in Figure 14.1, although other more sophisticated methods are available.79

For example, Gilron et al.78 found that gabapentin and morphine together were synergistic in effect (although side effects were not reduced) - the results would be represented as points below the diagonal line on an isobologram.

Comparisons are more difficult when drug and psychological treatments are combined and lessons on this can be learnt from the psychiatry literature.80 Since treatment combinations may interact to produce improvements or adverse events in different measurement domains, multidimensional outcomes are especially valuable.

Dose of drug B

Figure 14.1 Isobologram. The points represent drug doses that result in a fixed clinical outcome (e.g. 30 percent pain reduction). Assuming that the effect of two drugs is simply additive, a series of trials of different combinations achieving the same clinical result will fall along the dotted line (X). Different drugs could alternatively: work synergistically to produce greater effect (e.g. point Y below the line); or interfere with (antagonize) each others' actions, such that a higher dose of each is required for the same effect (points for equivalent effect would be above the line, e.g. Z).

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