How Do I Interpret Medical Literature On Peyronie''''s Disease Treatments?
Dr. John P. Mulhall M.D.

A few things about Peyronie''''s disease make it relatively unique among medical conditions and impact upon how information on treatments should be analyzed. Firstly, the disease has distinct phases; the acute phase is present during the inflammatory response to the injury, a time when men often complain of pain in the flaccid state and generally prior to or soon after the development of a noticeable plaque (some men will have tenderness in their plaque on examination during this phase); the chronic phase occurs after the maturation of the plaque and after the inflammatory reaction has settled down. It is believed by many authorities that medical therapies are most probably best started during or as close to the inflammatory response as possible.

The second factor that impacts upon interpretation of medical literature is the fact that Peyronie''''s disease has a variable course between individuals, for example, one man may have an inflammatory phase that may last months, while for others it may last less than a month. Likewise pain may last for a year in the occasional man while in some there no pain is complained of at any time. In some men the condition can be progressive (worsening deformity) and in some the progression can be very aggressive (some men going from a completely straight penis to a 45 degree curvature in a matter of a couple of weeks); in some men the deformity may not change at all and in yet more men (the minority) the deformity improves without any intervention over the first year of the condition. Exactly what proportion of patients fall into each category (worsening, stable and improving) is difficult to define from the medical literature, but experts agree that the proportion that improves spontaneously without treatment is small (and in my Peyronie''''s disease practice it is around 10% of men).

With these 2 factors in mind, this educational segment is geared towards the man with Peyronie''''s disease who has no medical training, in an effort to help him look at the medical literature and decide whether a particular treatment appears to have any positive effect on this condition. Firstly, a few terms should be defined: a prospective trial (study and trial are generally interchangeable) means that the information was collected in a forward manner, that is, that the first information was gathered when the patient first arrived from evaluation and each time he came back for review more information was gathered. This is the most accurate form of study as it generally ensures that identical information is collected on every patient in the study. In contrast to this kind of study a retrospective study collects information in a backward manner after all treatments have been conducted (where the doctor/researcher looks back through patients medical records and tries to gather as much information as possible). This is far less accurate and looked upon less favorably by researchers.

Placebo-controlled refers to the fact some men in the study were treated with placebo (sugar pill) while other men were treated with the medication being studied. This is the most accurate means of defining how good a drug treatment is. This is especially important in Peyronie''''s disease as some men (as explained above) may improve their penile deformity without any treatment. Therefore, when you are reading a medical paper on results from a treatment, you have to ask yourself the question: "what percentage of men in this study might have improved anyway without this drug therapy?" It is possible that many studies that are not placebo-controlled over-estimate the effectiveness of medication. In studies that do not use drugs but use other technologies (for example, ESWT or vacuum devices in Peyronie''''s disease) a control arm of the study should be conducted. This means that in a study assessing ESWT, some men should receive ESWT but others should receive "fake" ESWT. In this way, once again, an accurate assessment of the real effectiveness of therapy can be measured. The most reliable controlled studies are blinded; single-blinded refers to a study in which the patient does not know what he is receiving and a double-blinded study refers to studies in which both patient and physician do not know what treatment the patient is receiving. Double-blinded studies are the most accurate because they minimize the risk of any bias that the physician may introduce by wanting the treatment to be effective. For example the most important studies conducted on new drugs by the FDA are double-blind, placebo-controlled trials where a sugar pill is always used and neither patient or physician know exactly what the patient is receiving. Unfortunately, most Peyronie''''s disease treatment studies are conducted in a non-blinded and non-controlled fashion and this undermines the accuracy and reliability of the information in these studies.

The term end-point refers to what is being measured in the study. In Peyronie''''s disease studies there are a number of end-points that are analyzed, some of which are more important than others. Most experts would agree and most patients would admit that the most important end-point is penile deformity, whether that be curvature, indentation or hour-glass deformity (hinge-effect). Unfortunately, not all Peyronie''''s disease studies accurately measure this end-point. Penile deformity should be measured at the beginning of the trial and then after the trial has been completed. The most accurate means of determining the degree of deformity is to measure it during a fully rigid penile erection. This is best achieved following the administration of a penile injection of medication that can induce a full erection. To be most accurate this should be done at the beginning of the study and then repeated at the end of the study. Many trials that claim effectiveness of a drug or device have failed to do this and the results of these studies should be questioned. Furthermore, studies generally quote the percentage of men who had improvement in their deformity with a certain treatment. Often these figures include men with a 5 degree improvement in their curvature. In my practice, most patients feel that this is not a significant improvement (the average curvature at presentation in my practice is around 45 degrees, therefore a 5 degree change is perceived as minimal), furthermore, even in the erect state measurement of curvature with a protractor or goniometer (tool for measuring angulation) is prone to some error and 5 degrees falls within that error zone.

Another end-point analyzed is penile pain. In virtually all patients with Peyronie''''s disease who suffer from penile pain this has completely resolved within the first year of the disease. Therefore, the sue of a placebo or control arm in the study is essential to define if the treatment really caused the pain to go away or if this is the natural history of the condition. Thus, assessing pain in such studies is probably only minimally useful. A third end-point often analyzed is plaque volume. This refers to the size of the plaque and is most accurately defined by penile ultrasound. Once again, a placebo or control arm is necessary to answer whether any change in plaque volume is the result of the treatment or the natural course of the disease. Of note, some plaques as they mature contract and naturally get smaller so a reduction in size of a plaque may not always be a good thing. Indeed, as some plaque gets smaller the degree of deformity may increase. A fourth end-point is sexual (erectile) function that is the ability of the patient to have sexual intercourse. It is suggested that some treatments can improve sexual function in some men, however the means by which this information is gathered can make these figures questionable. This is an end-point that needs to be assessed in a prospective fashion as if it is assessed in a retrospective fashion (asking a patient a year after the onset of the Peyronie''''s disease about his sexual function 18 months prior is notoriously accurate - the term for this error is recall bias - can you remember how good your erections were 18 months ago?) the answers are often inaccurate. Furthermore, a physician simply asking his patient can he have sex or not is not a reliable way of defining this. There are questionnaires that can be used to answer this question, which if given at the start and end of the study will more accurately answer the sexual function question.

In fairness to Peyronie''''s disease researchers, designing the perfect study is difficult, indeed, virtually impossible. Questions that often arise at medical conferences pertaining to Peyronie''''s disease research studies include, how long should a patient have Peyronie''''s disease for before he is excluded from a study? Is there a limit on the degree of curvature that is allowed in the study? How long should the treatment be used for? How long after treatment should the patient be followed for? We as experts in Peyronie''''s disease have not answered all of these issues yet.

In summary, do not believe all that you read. Be critical of results. Look for whether the study was sponsored by a company, if so this may introduce bias, particularly if the study was not done in a placebo-controlled fashion. Look for the number of patients in the study, the more the better. The recent WHO-sponsored international consultation on sexual dysfunction had a panel on Peyronie''''s disease (on which I sat) and studies to be included in the analysis had to have at least 50 patients. Look for how the authors defined success. Look for how long patients had Peyronie''''s disease, were they in the acute or chronic phase? Look for side effects of treatment, very few treatments are without side effects.