A patient has recurrent herpes genitalis and is interested to know how episodic treatment with a new antiviral drug will improve the signs and symptoms of his recurrences. The physician has a copy of the results of a pertinent clinical trial (8
). Cox proportional hazards regression was used to analyze the healing time, and a hazard ratio of 1.9 (95% confidence interval, 1.6 to 2.3) was reported for the lower of two drug doses tested. The median healing time was reduced by approximately 2 days, or 33%. The Kaplan-Meier curve is shown in Fig. . The questions and the recommended responses by the physician are followed by a brief discussion. A fundamental challenge for the physician is to understand that the patient is asking about him- or herself, while the data by which the physician answers his or her questions derives from a population.
Q: Doctor, does this drug really work?
A: Yes, a clinical study has shown that the new drug promotes healing.
The hazard ratio is a clinical trial statistic that allows the physician to say with confidence that healing is faster with the new drug. The hazard ratio must be >1 and the lower limit of the 95% confidence interval of the hazard ratio must be >1, which was the case in this example.
Q: Doctor, what are the chances I will do better on this new drug compared to no treatment?
A: The odds are roughly 2:1 (the probability is 66%) that you will have an episode of shorter duration than someone who did not take the drug.
The odds are equal to the hazard ratio, which is 1.9 in the present case. The probability of healing sooner can be derived from the hazard ratio by the following formula: HR = odds = P/(1 − P); P = HR/(1 + HR). And so, in this example, P = 1.9/2.9 = 0.67.
It is unfortunately not absolutely certain that you will heal faster on this drug. There are two factors that influence the lesion healing time: the effect of the drug and natural variation in episode severity, so that some lesions will be very brief among untreated patients.
Q: Doctor, when will I heal if I use the new drug?
A: The study showed that about half the people who used the new drug healed within 4 days, and 95% healed within 8 days. Your experience will vary, like those of the people in the study, because of the natural variation in severity characteristic of this illness.
The question of timing can be expressed in several different ways. How likely is it that I will heal in a certain number of days if I use this treatment? By what day will I have a certain likelihood of healing? Answers to these questions can be determined from the Kaplan-Meier curve (see Fig. ). Healing times cannot be deduced from the hazard ratio unless the data are fit to an underlying parametric survival distribution (4
Q: Doctor, how much good will this drug do for me?
A: The new drug reduced the healing time in the study compared to the placebo group by about a third. Drug-treated patients had a median healing time of 4 days, compared to 5.9 days for the placebo recipients. If you use the new drug properly over a period of time, you can expect approximately this amount of benefit in comparison to what might have happened if you had let your lesions go untreated.
Reduction in the healing time can be estimated from the median healing times of the treated and placebo groups as shown in the survival curve. Here the patient is thinking of himself as two persons, one who takes the drug for recurrent herpes episodes over a period of time and one who does not take the drug. If taken properly, the drug should provide to an individual, compared to the hypothetical situation where one does not take the medication, approximately the same benefit calculated in the study from the difference between the healing times of the two treatment groups. This is the closest we can come to personalizing clinical trial results when discussing prospective treatment with a patient. While there may be pathophysiologic reasons for believing a patient will receive a certain degree of benefit every time the medication is taken, clinical data only allow comparisons between groups of individuals. As pharmaceutical company commercials on television warn, “individual results may vary.”