Future Research Recommendations

Efforts are needed to improve the quality of reporting primary studies (i.e., randomized trials). The CONSORT Statement could be considered as a reporting guide for authors reporting trials and journals that publish ED-related research.³⁹⁵

Future studies should focus on both short- and long-term (6 months or longer) clinically relevant valid treatment outcomes. Such studies could clarify important unanswered questions involving both realms of efficacy and harms as well as evaluate relative sustainability of the clinical benefit conferred by different treatment modalities. Additional research should evaluate patient preferences, satisfaction, and compliance with different treatments, including PDE-5 inhibitors. Well designed longer-term RCTs evaluating the effects of PDE-5 inhibitors or other therapies will allow better documentation of the incidence of specific adverse events (e.g. mortality, cardiovascular events, visual disturbances, NAION, penile fibrosis). In light of the presence of comorbidities or causes underlying ED, the comparison of cause-specific therapies (administered alone or in combination) with the first-line treatment(s) in terms of efficacy and safety profiles is warranted. The trials should be more population-based to maximize the degree of external validity of their results.

More trials in clinically homogenous subgroups of ED patients presenting with concomitant conditions (e.g. diabetes, cardiovascular disease, prostate cancer, high blood pressure) are needed to better explore and characterize potential treatment effect modification. Additional investigations of treatment effects in patient subgroups defined by severity, duration, and etiology of ED are also warranted as are therapeutic trials in different ethnic groups of patients with ED.

More efforts are needed to elucidate the minimum clinically important difference (MCID) for the validated and clinically relevant outcomes (e.g. mean scores on IIEF, SEP, proportion of patients with improved erection) for various situations (e.g. patient subgroups, instruments used to measure change in the outcome, self-, partner- or investigator-reported).

Further research is warranted to determine the utility of routine endocrinological blood tests (e.g. serum testosterone, prolactin levels). This would involve studies with large and representative samples of ED patients to estimate precisely the age-stratified prevalence rates for endocrinological abnormalities (e.g. hypogonadism, hyperprolactinemia) and to determine subgroups (or risk factors) of patients with ED who have increased risk of hypogonadism. Ultimately, routine endocrinological blood tests (e.g. total, free, bioavailable) need to be standardized.³⁹⁶

Ideally, studies of testosterone used for the treatment of ED should enroll men with testosterone deficiency. If men with higher testosterone levels are to be included in these trials, stratified analyses should be conducted based on baseline testosterone levels. More data from large trials regarding the safety of long-term use of testosterone therapy is needed for more definitive conclusions.

Future trials of intracavernosal injection treatments should focus on clinically relevant efficacy and harm-related outcomes such as the degree of ED/treatment satisfaction (e.g. scores for International Index of Erectile Function, Erectile Dysfunction Index of Treatment Satisfaction), sexual intercourse success rate (Sexual Encounter Profile scores), penile pain, fibrosis, and priapism. The analyses should include all randomized participants in order to reduce the potential for selection bias (i.e. intention-to-treat analysis).