Wade R Gutierrez et al., 2024: Variability in methodology of erectile dysfunction regenerative therapy trials on ClinicalTrials.gov

Tuesday, 03 September 2024

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Wade R Gutierrez 1 , Martin S Gross 2 , Matthew J Ziegelmann 3
1Medical Scientist Training Program, University of Iowa, Iowa City, IA.
2Section of Urology, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
3Department of Urology, Mayo Clinic, Rochester, MN.

Abstract

Objective: To evaluate the variability in the criteria of erectile dysfunction (ED) regenerative therapy trials registered on ClinicalTrials.gov.

Methods: Interventional trials on ClinicalTrials.gov with the keywords "erectile dysfunction" and variations of "shockwave," "platelet rich plasma," "stem cell," "regenerative," and "restorative" were examined. Inclusion/exclusion criteria and primary/secondary outcomes were compared between extracorporeal shockwave therapy (ESWT), platelet rich plasma and stem cell injections (PRP/SC), and other regenerative therapies (ORT) groups.

Results: Of the 92 trials analyzed, International Index of Erectile Function (IIEF) score was the most common primary outcome (72%), with a higher prevalence in ESWT trials than PRP/SC or ORT trials (89% vs 44% and 58%, P <.001). Safety/tolerability was a primary outcome for 44% of PRP/SC trials and 25% of ORT trials but no ESWT trials (P <.001). ESWT trials more frequently had sexual/romantic relationship-based inclusion criteria and cancer treatment-related exclusion criteria than PRP/SC and ORT trials.

Conclusion: There is substantial variability in the inclusion/exclusion criteria and outcome measures among ED regenerative therapy trials. ESWT trials most frequently utilized IIEF and had the strictest inclusion/exclusion criteria, suggesting more rigorous and functional outcome-based studies. Conversely, PRP/SC and ORT trials, but not ESWT trials, had safety/tolerability as a primary outcome, likely due to the experimental nature of these therapies. The variability in inclusion/exclusion criteria and outcome measures limits comparison of the various ED regenerative therapies.

Urology. 2024 May 20:S0090-4295(24)00370-4. DOI: 10.1016/j.urology.2024.05.016. Online ahead of print. PMID: 38777189

Comments 1

Jens Rassweiler on Tuesday, 03 September 2024 11:00

This article examines the inconsistency in clinical trials focused on regenerative therapies for erectile dysfunction (ED). ED is a common urological condition that has significant quality-of-life and economic impacts. Traditional treatments include medications, devices, and surgery, but newer regenerative therapies like extracorporeal shockwave therapy (ESWT), platelet-rich plasma (PRP) injections, and stem cell therapy (SCT) have emerged, aiming to cure rather than just manage symptoms.
Key Findings:
1. Lack of Standardization: The study highlights that there is no standard set of inclusion or exclusion criteria, nor is there a consistent approach to measuring outcomes across trials. This lack of standardization makes it difficult to compare the effectiveness and safety of different regenerative therapies.

2. Common Criteria: Despite the variability, some criteria were used in over 50% of the trials. These include a maximum erectile function limit, which was present in 79% of trials, and the use of the International Index of Erectile Function (IIEF) score as a primary outcome in 72% of trials. In summary, the authors believe that establishing more standardized and objective criteria, such as Color Duplex ultrasound and nocturnal erection measurements, would improve the ability to evaluate and compare the effects of regenerative therapies for ED, leading to better understanding and potentially better treatment options.

3. Differences by Therapy Type: The study found significant differences in how criteria were applied depending on the type of regenerative therapy being studied. For instance, ESWT trials often had more stringent criteria, particularly concerning the patient’s sexual and romantic relationship status. On the other hand, PRP/SCT trials more frequently focused on safety and tolerability as primary outcomes, reflecting their more experimental nature.

4. Inconsistent Outcome Measures: While IIEF scores were the most common primary outcome, the degree of improvement considered clinically significant was rarely defined. This further complicates the comparison of results across studies.
Discussion: The article underscores the challenges posed by the variability in clinical trial methodologies for ED regenerative therapies. This inconsistency limits the ability of healthcare providers to make informed decisions about these treatments, as it is challenging to assess the relative safety and effectiveness of different therapies. The article suggests that standardization of trial criteria could improve the comparability of studies, ultimately aiding in the establishment of regenerative therapies as viable treatments for ED.
Conclusion: The article concludes that the substantial variability in trial criteria for ED regenerative therapies hinders the assessment and comparison of these treatments. To improve the reliability and applicability of future studies, there is a pressing need for standardized trial designs. This would facilitate the development of evidence-based guidelines and ultimately lead to better patient outcomes in the treatment of ED with regenerative therapies.
Implications: Three issues should be taken into consideration.
Regulatory Oversight: The findings suggest a need for greater regulatory oversight and standardization in the design of clinical trials for ED regenerative therapies. This could involve guidelines from professional organizations like the American Urological Association.
Patient Impact: For patients, the current lack of standardization means that it is difficult to know which regenerative therapy, if any, is most likely to be effective. This could lead to patients spending significant money on treatments with unproven efficacy.
Future Research: The article highlights the importance of future research focusing not only on the development of new therapies but also on the standardization of trial methodologies. This would enable better comparison of outcomes and help identify which therapies are truly beneficial.

Jens Rassweiler

2.	Common Criteria: Despite the variability, some criteria were used in over 50% of the trials. These include a maximum erectile function limit, which was present in 79% of trials, and the use of the International Index of Erectile Function (IIEF) score as a primary outcome in 72% of trials. In summary, the authors believe that establishing more standardized and objective criteria, such as Color Duplex ultrasound and nocturnal erection measurements, would improve the ability to evaluate and compare the effects of regenerative therapies for ED, leading to better understanding and potentially better treatment options.

3.	Differences by Therapy Type: The study found significant differences in how criteria were applied depending on the type of regenerative therapy being studied. For instance, ESWT trials often had more stringent criteria, particularly concerning the patient’s sexual and romantic relationship status. On the other hand, PRP/SCT trials more frequently focused on safety and tolerability as primary outcomes, reflecting their more experimental nature.

4.	Inconsistent Outcome Measures: While IIEF scores were the most common primary outcome, the degree of improvement considered clinically significant was rarely defined. This further complicates the comparison of results across studies.
Discussion: The article underscores the challenges posed by the variability in clinical trial methodologies for ED regenerative therapies. This inconsistency limits the ability of healthcare providers to make informed decisions about these treatments, as it is challenging to assess the relative safety and effectiveness of different therapies. The article suggests that standardization of trial criteria could improve the comparability of studies, ultimately aiding in the establishment of regenerative therapies as viable treatments for ED.
Conclusion: The article concludes that the substantial variability in trial criteria for ED regenerative therapies hinders the assessment and comparison of these treatments. To improve the reliability and applicability of future studies, there is a pressing need for standardized trial designs. This would facilitate the development of evidence-based guidelines and ultimately lead to better patient outcomes in the treatment of ED with regenerative therapies.
Implications: Three issues should be taken into consideration.
Regulatory Oversight: The findings suggest a need for greater regulatory oversight and standardization in the design of clinical trials for ED regenerative therapies. This could involve guidelines from professional organizations like the American Urological Association.
Patient Impact: For patients, the current lack of standardization means that it is difficult to know which regenerative therapy, if any, is most likely to be effective. This could lead to patients spending significant money on treatments with unproven efficacy.
Future Research: The article highlights the importance of future research focusing not only on the development of new therapies but also on the standardization of trial methodologies. This would enable better comparison of outcomes and help identify which therapies are truly beneficial.

Jens Rassweiler

This article examines the inconsistency in clinical trials focused on regenerative therapies for erectile dysfunction (ED). ED is a common urological condition that has significant quality-of-life and economic impacts. Traditional treatments include medications, devices, and surgery, but newer regenerative therapies like extracorporeal shockwave therapy (ESWT), platelet-rich plasma (PRP) injections, and stem cell therapy (SCT) have emerged, aiming to cure rather than just manage symptoms. Key Findings: 1. Lack of Standardization: The study highlights that there is no standard set of inclusion or exclusion criteria, nor is there a consistent approach to measuring outcomes across trials. This lack of standardization makes it difficult to compare the effectiveness and safety of different regenerative therapies. 2. Common Criteria: Despite the variability, some criteria were used in over 50% of the trials. These include a maximum erectile function limit, which was present in 79% of trials, and the use of the International Index of Erectile Function (IIEF) score as a primary outcome in 72% of trials. In summary, the authors believe that establishing more standardized and objective criteria, such as Color Duplex ultrasound and nocturnal erection measurements, would improve the ability to evaluate and compare the effects of regenerative therapies for ED, leading to better understanding and potentially better treatment options. 3. Differences by Therapy Type: The study found significant differences in how criteria were applied depending on the type of regenerative therapy being studied. For instance, ESWT trials often had more stringent criteria, particularly concerning the patient’s sexual and romantic relationship status. On the other hand, PRP/SCT trials more frequently focused on safety and tolerability as primary outcomes, reflecting their more experimental nature. 4. Inconsistent Outcome Measures: While IIEF scores were the most common primary outcome, the degree of improvement considered clinically significant was rarely defined. This further complicates the comparison of results across studies. Discussion: The article underscores the challenges posed by the variability in clinical trial methodologies for ED regenerative therapies. This inconsistency limits the ability of healthcare providers to make informed decisions about these treatments, as it is challenging to assess the relative safety and effectiveness of different therapies. The article suggests that standardization of trial criteria could improve the comparability of studies, ultimately aiding in the establishment of regenerative therapies as viable treatments for ED. Conclusion: The article concludes that the substantial variability in trial criteria for ED regenerative therapies hinders the assessment and comparison of these treatments. To improve the reliability and applicability of future studies, there is a pressing need for standardized trial designs. This would facilitate the development of evidence-based guidelines and ultimately lead to better patient outcomes in the treatment of ED with regenerative therapies. Implications: Three issues should be taken into consideration. Regulatory Oversight: The findings suggest a need for greater regulatory oversight and standardization in the design of clinical trials for ED regenerative therapies. This could involve guidelines from professional organizations like the American Urological Association. Patient Impact: For patients, the current lack of standardization means that it is difficult to know which regenerative therapy, if any, is most likely to be effective. This could lead to patients spending significant money on treatments with unproven efficacy. Future Research: The article highlights the importance of future research focusing not only on the development of new therapies but also on the standardization of trial methodologies. This would enable better comparison of outcomes and help identify which therapies are truly beneficial. Jens Rassweiler

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