To the editor: understanding presperm retrieval hormonal treatment effectiveness in nonobstructive azoospermia through real-world evidence

Stakeholders in healthcare are increasingly turning to real world evidence (RWE) to inform their decisions, alongside evidence from randomized controlled trials. RWE is generated by analysing data gathered from routine clinical practice, and can be used across the product lifecycle, providing insights into areas including disease epidemiology, treatment effectiveness and safety, and health economic value and impact. Recently, the US Food and Drug Administration and the European Medicines Agency have stated their ambition for greater use of RWE to support applications for new indications, and are now consulting with their stakeholders to formalize standards and expected methods for generating RWE. Pharmaceutical companies are responding to the increasing demands for RWE by developing standards and processes for each stage of the evidence generation pathway. Some conventions are already in place for assuring quality, whereas other processes are specific to the research question and data sources available. As evidence generation increasingly becomes a core role of medical affairs divisions in large pharmaceutical companies, standards of rigour will continue to evolve and improve. Senior pharmaceutical leaders can drive this change by making RWE a core element of their corporate strategy, providing top-level direction on how their respective companies should approach RWE for maximum quality. Here, we describe the current and future areas of RWE application within the pharmaceutical industry, necessary access to data to generate RWE, and the challenges in communicating RWE. Supporting and building on viewpoints from industry and publicly funded research, our perspective is that at each stage of RWE generation, quality will be critical to the impact that RWE has on healthcare decision-makers; not only where RWE is an established and evolving tool, but also in new areas that have the potential to disrupt and to improve drug development pathways.

Payers are faced with making coverage and reimbursement decisions based on the best available evidence. Often these decisions apply to patient populations, provider networks, and care settings not typically studied in clinical trials. Treatment effectiveness evidence is increasingly available from electronic health records, registries, and administrative claims. However, little is known about when and what types of real-world evidence (RWE) studies inform pharmacy and therapeutic (P&T) committee decisions. To evaluate evidence sources cited in P&T committee monographs and therapeutic class reviews and assess the design features and quality of cited RWE studies. A convenience sample of representatives from pharmacy benefit management, health system, and health plan organizations provided recent P&T monographs and therapeutic class reviews (or references from such documents). Two investigators examined and grouped references into major categories (published studies, unpublished studies, and other/unknown) and multiple subcategories (e.g., product label, clinical trials, RWE, systematic reviews). Cited comparative RWE was reviewed to assess design features (e.g., population, data source, comparators) and quality using the Good ReseArch for Comparative Effectiveness (GRACE) Checklist. Investigators evaluated 565 references cited in 27 monographs/therapeutic class reviews from 6 managed care organizations. Therapeutic class reviews mostly cited published clinical trials (35.3%, 155/439), while single-product monographs relied most on manufacturer-supplied information (42.1%, 53/126). Published RWE comprised 4.8% (21/439) of therapeutic class review references, and none (0/126) of the monograph references. Of the 21 RWE studies, 12 were comparative and assessed patient care settings and outcomes typically not included in clinical trials (community ambulatory settings [10], long-term safety [8]). RWE studies most frequently were based on registry data (6), conducted in the United States (6), and funded by the pharmaceutical industry (5). GRACE Checklist ratings suggested the data and methods of these comparative RWE studies were of high quality. RWE was infrequently cited in P&T materials, even among therapeutic class reviews where RWE is more readily available. Although few P&T materials cited RWE, the comparative RWE studies were generally high quality. More research is needed to understand when and what types of real-world studies can more routinely inform coverage and reimbursement decisions. This project was funded by the National Pharmaceutical Council. Hurwitz, Brown, Peters, and Malone have nothing to disclose. Graff is employed by the National Pharmaceutical Council Part of this study was presented as a poster presentation at the AMCP Managed Care & Specialty Pharmacy 2016 Annual Meeting; April 19-22, 2016; San Francisco, CA. Study concept and design were primarily contributed by Malone and Graff, along with Hurwitz and Brown. All authors participated in data collection, and data interpretation was performed by Malone, Hurwitz, and Graff, with assistance from Brown and Peters. The manuscript was written primarily by Hurwitz and Malone, along with Graff, Brown, and Peters, and revised by Malone, Brown, Peters, Hurwitz, and Graff.

One major challenge in male factor infertility is nonobstructive azoospermia (NOA), which is characterized by spermatozoa-deficient semen without physical duct blockage. This review offers a thorough overview of the histopathology of the testes in NOA cases, clarifying its complex etiology and emphasizing the possible value of histopathology inspection for both diagnosis and treatment. Variable histopathological findings have been linked to NOA, such as tubular hyalinization, Sertoli cell-only syndrome, hypospermatogenesis, and germ cell arrest. Understanding the pathophysiology and forecasting the effectiveness of treatment are further enhanced by both morphometric and ultrastructural analyses. The potential significance of testicular biopsy in forecasting reproductive outcomes is assessed, especially concerning assisted reproductive technologies like intracytoplasmic sperm injection (ICSI). Besides, testicular microlithiasis, serum hormone profiles, and testicular size are investigated concerning NOA histopathology. It is concluded that understanding the histopathological patterns in NOA is crucial for its accurate diagnosis and appropriate management. Further research is still warranted to improve understanding of the complex pathophysiology underlying NOA.

To date, no randomized and controlled study has demonstrated the effect of adjuvant medical therapy on testicular sperm production before the sperm retrieval procedures in men with non-obstructive azoospermia (NOA). To present the available data on the administration of pharmaceutical agents prior to testicular sperm extraction (TESE) procedures in order to obtain better sperm retrieval results in men with NOA. Various pharmaceutical agents were used empirically to induce spermatogenesis in the treatment of NOA. The rationale for adjuvant hormonal treatment has been to increase intratesticular testosterone levels with different dosages of gonadotropins, anti-estrogen agents, or aromatase inhibitors. Based on the published studies, in the presence of a normal range of peripheral serum total testosterone levels, no medical treatment is advised, and TESE procedures should be performed directly in men with NOA. Further well-designed and randomized, placebo-controlled trials are needed to support the potential benefit of pretreatment prior to TESE procedures.

Background: The combination of trastuzumab, pertuzumab, and docetaxel (THP) has been established as a standard first-line treatment for HER2-positive metastatic breast cancer, following the CLEOPATRA study, which demonstrated the added efficacy of pertuzumab compared to placebo with trastuzumab and docetaxel. In the CLEOPATRA study and previous real-world evidence studies, patients who discontinue docetaxel due to adverse events after the induction period continue HER2 blocking treatment with trastuzumab and pertuzumab (HP). In the era of trastuzumab deruxtecan introduction in earlier treatment lines, it is important to evaluate the effectiveness of the THP treatment, especially long-term continuous HP without docetaxel, as a meaningful option for the quality of life of patients, by utilizing real-world evidence (RWE). Methods: We conducted a retrospective analysis of 320 HER2-positive patients who began receiving THP treatment at Samsung Medical Center between April 2015 and December 2021. This analysis utilized de-identified and anonymous data from the Clinical Data Warehouse based on institutional real-world electronic medical data. Patients included in the study received at least one cycle of THP. The cutoff date for the analysis was 31st May 2024. The primary outcomes of the study were Progression-Free Survival (PFS) and Overall Survival (OS). The secondary outcome assessed the OS differences between different subgroups. Result: The median follow up was 46.8 months (range 0.35-109.1). Among 320 patients, 151 patients (47.2%) were hormone receptor (HR) negative, while 133 patients (41%) were HR positive either estrogen receptor or progesterone receptor. The median cycle of the THP was 22 cycles (range 1-158) and the median cycle of docetaxel was 8 cycles (range 1-34). Median PFS was 30.8 months and median OS was not yet reached. In our study, the median number of cycles of HP after discontinuation of docetaxel was 12 cycles (range 0-144). Sixty-six patients (20.6%) maintained HP for more than 3 years, 37 patients (11.6%) received it for more than 4 years, and even 23 patients (7.2%) continued HP for more than 5 years. The median number of cycles of HP was 3 (range 0-103), 14 (range 0-128), and 17 (range 0-144) in patient groups who received fewer than 6 cycles of docetaxel (50 patients, 15.6%), 6-10 cycles (200 patients, 62.5%), and more than 10 cycles (70 patients, 21.9%), respectively. Patients who received fewer than 6 cycles of docetaxel showed significantly poorer survival outcomes compared to the other groups (6-10 cycles of docetaxel: HR = 0.39, 95% CI 0.24-0.64, p = 0.0001; more than 10 cycles of docetaxel: HR = 0.25, 95% CI 0.13-0.48, p < 0.0001). However, the overall survival between the patient group who received 6-10 cycles of docetaxel and the group who received more than 10 cycles of docetaxel showed no significant differences (HR = 0.62, 95% CI 0.34-1.15, p = 0.13). Conclusion: Our findings are consistent with the survival benefit of the THP regimen in real-world practice, aligning with the results of the randomized clinical trial, CLEOPATRA. This study highlights that HP after the induction phase with docetaxel is a clinically meaningful treatment option, considering both patients’ quality of life and survival benefit. This study showed a relevantly longer survival outcome compared to CLEOPATRA, addressing diversity and healthcare system-specific variations in treatment outcomes that may not be fully captured by global clinical trials. While acknowledging the limitations in generalizability inherent in this single-center, retrospective analysis, the study provides valuable insights into the effectiveness of this treatment regimen in a Korean population, contributing to the broader understanding of its performance in Asian patients. Our results underscore the importance of RWE in complementing clinical trial findings and optimizing treatment strategies for HER2-positive metastatic breast cancer patients. Citation Format: Min Jeong Kim, Hyo Jung Kim, Jin Seok Ahn, Ji-Yeon Kim, Junghoon Shin, Yeon Hee Park. The Effectiveness of Trastuzumab, Pertuzumab and Docetaxel Combination as a First-Line Treatment of HER2-Positive Metastatic Breast Cancer Patients : A Real-World Evidence in Korea [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-12-06.

Noncommunicable diseases (NCDs) are the leading causes of mortality and morbidity across the world and factors influencing global poverty and slowing economic development. We summarize how the potential power of real-world data (RWD) and real-world evidence (RWE) can be harnessed to help address the disease burden of NCDs at global, national, regional and local levels. RWE is essential to understand the epidemiology of NCDs, quantify NCD burdens, assist with the early detection of vulnerable populations at high risk of NCDs by identifying the most influential risk factors, and evaluate the effectiveness and cost-benefits of treatments, programs, and public policies for NCDs. To realize the potential power of RWD and RWE, challenges related to data integration, access, interoperability, standardization of analytical methods, quality control, security, privacy protection, and ethical standards for data use must be addressed. Finally, partnerships between academic centers, governments, pharmaceutical companies, and other stakeholders aimed at improving the utilization of RWE can have a substantial beneficial impact in preventing and managing NCDs.

The possibility of stimulating the recovery of spermatogenesis after irradiation using hormone treatment was tested in LBNF, rats. At 10 weeks after irradiation with 3.5 Gy, the percentage of tubules showing recovery of spermatogenesis (repopulation index) was 37% in rats that received no hormone treatment. GnRH agonist (GnRH-Ag) treatment with Zoladex or continuous treatment with testosterone markedly stimulated the recovery of spermatogenesis. When GnRH-Ag treatment was started immediately after 3.5-Gy irradiation and maintained for 10 weeks, the repopulation index was 91%. When an additional 6.5 weeks without further treatment was allowed between the 10-week GnRH treatment and killing the rats, the repopulation index recovered to 100% and sperm counts to 83 x 10(6). These sperm counts were more than 100-fold higher than those in rats not given hormone treatment and 50% of normal nonirradiated control levels. GnRH-Ag for 10 weeks also stimulated spermatogenic recovery in rats irradiated with 6 Gy, even when the start of treatment was delayed until 18 weeks after irradiation. Without GnRH-Ag, the repopulation index was 0, but in GnRH-Ag-treated rats it was 14.5%. Since all of the hormone treatments suppress intratesticular testosterone, high levels of testosterone may be inhibiting differentiation and their suppression may stimulate recovery. Even though the exact mechanism is not yet known, this method may still be applicable for clinical use to activate spermatogenesis in patients rendered azoospermic by irradiation or possibly by other cytotoxic treatments.

Background Mirikizumab is approved for adults with moderate-to-severe ulcerative colitis (UC) based on evidence from randomised clinical trials.1 However, real-world evidence on treatment persistence and clinical outcomes in routine practice is limited. This analysis evaluated treatment persistence and effectiveness among patients with UC receiving mirikizumab in a Canadian real-world setting. Methods Adults (≥18 years) with moderate-to-severe UC enrolled in the LillyPlus® Patient Support Program in Canada who received at least 1 dose of mirikizumab (index date) between 26 October 2023 and 28 April 2025 were included. Persistence was defined as continuous mirikizumab treatment until reported discontinuation.2 Clinical outcomes assessed included bowel urgency (BU; scored 0-10), rectal bleeding (RB; scored 0-3), and stool frequency (SF; scored 0-3), with higher scores indicating more severe symptoms/higher symptom severity. Scores were collected at baseline and at weeks 4, 12, and 24 (+4-week window after each touchpoint). Persistence and clinical outcomes were evaluated up to 24 weeks post-index by prior advanced therapy (AT) subgroup (AT-naïve and AT-experienced) using descriptive statistics. Results The cohort (N = 774) was 51.9% female with a mean (standard deviation [SD]) age of 46.5 (17.4) years, and 87.0% of participants were AT-experienced. Treatment persistence rates were 98.0%, 92.6%, and 80.9% at 4, 12, and 24 weeks, respectively (Figure 1). Persistence rates trended higher in AT-naïve than in AT-experienced patients at week 24. At baseline, the overall mean (SD) BU, RB, and SF scores were 6.83 (2.90), 1.41 (1.08), and 2.22 (1.05), respectively (Figure 2). Changes to outcome scores were observed as early as week 4. By week 24, the overall mean (SD) BU, RB, and SF scores had decreased to 2.98 (2.67), 0.44 (0.72), and 0.86 (0.92), respectively. Conclusion In this real-world setting, which included a high proportion of AT-experienced participants (87.0%), mirikizumab demonstrated treatment persistence through 24 weeks of initial treatment. Improvements in BU, RB, and SF scores were observed as early as 4 weeks and continued over 24 weeks in both AT-naïve and AT-experienced patients.

e17571 Background: Women diagnosed with advanced or recurrent endometrial cancer (EC) have a poor prognosis, with a 5-year survival of only 15% to 17%. While a multi-modality approach is often used for newly diagnosed EC including platinum-based chemotherapy, there are no definitively approved standard treatment options for advanced or recurrent EC following prior systemic therapy (FPST). The real-world evidence surrounding the effectiveness of chemotherapies in this setting is not well characterized. We conducted a systematic literature review to attempt to fill this evidence gap. Methods: Systematic searches were run in Embase, MEDLINE, and the Cochrane Library to identify English-language publications from January 2000 to July 2020. Additional hand searches of 5 key conferences held from 2018 to 2020 were also conducted. The review included observational studies reporting the clinical effectiveness, safety, or treatment patterns of pharmacological treatments in adult women with advanced or recurrent EC. Results: Seventy-seven observational studies met the inclusion criteria, of these 63 studies reported on the effectiveness of chemotherapies. While 57 studies described adjuvant chemotherapy use, 6 described use of chemotherapies FPST, including 1 study in the second line or later. Only one of these 6 studies reported a sample size greater than 100 patients. Chemotherapy FPST included paclitaxel/carboplatin (3 studies), doxorubicin (2 studies), etoposide (1 study), or any platinum-based chemotherapy (1 study). Shorter median overall survival (OS) was observed in patients with treatment-free intervals (TFI) < 6 months from prior systemic therapy (5.5-11.3 months; 2 studies) compared to those with TFI > 6 months (13.0-27.0 months; 3 studies). Similarly, shorter median progression-free survival (PFS) was seen in patients with TFI < 6 months from prior systemic therapy (2.0-3.2 months; 2 studies) vs. those with TFI > 6 months (6.0-10.0 months; 3 studies). Conclusions: Women with advanced or recurrent EC have poor OS and PFS with current chemotherapy regimens, especially for those with TFI < 6 months. The time at recurrence from prior systemic therapy seems to correlate with the outcomes of subsequent treatment. Novel efficacious treatment strategies are required to improve patients’ outcomes in the FPST setting. While extensive real-world evidence exists for patients with EC receiving adjuvant chemotherapy, real world data is limited for use of chemotherapy in advanced or recurrent setting, warranting further research in larger samples of patients.

BackgroundDiabetes is a progressive disease needing multiple drugs for achieving and maintaining good glycemic control. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) is a novel class of anti-diabetic agent which offers several beneficial effects. However, the long-term effectiveness in clinical practice and safety data of SGLT2 inhibitors is limited, especially in Asian patients. To better understand the effectiveness of SGLT2i in clinical practice, we conducted a retrospective evaluation of patients with diabetes on SGLT2i.MethodsThis retrospective observational study uses data of patients with diabetes who had been prescribed SGLT2i and continued to use at least 6 months at Theptarin Hospital, Bangkok. The characteristics of patients, changes in glycemic control and body weight at 3, 6, 12, 18, 24 months and the last follow-up were evaluated.ResultsA total of 189 patients with diabetes (females 50.3%, mean age 59.9 ± 12.3 years, T2DM 97.3%, duration of diabetes 16.3 ± 9.2 years, baseline BMI 29.9 ± 6.1 kg/m2, baseline HbA1c 8.8 ± 1.6%) were prescribed SGLT2i during the study period. At the time of first SGLT2i prescription, 80.4% used three or more other anti-diabetic agents concomitantly and 34.6% used insulin concomitantly. 151 patients who continue to use at least 6 months were included in analysis. At the last follow-up (median time 16 months), overall median HbA1c reduction and weight reduction were 1.0% and 1.5 kg, respectively. While glycemic control could maintain up to 18 months, weight loss gradually rebounded after the first 6 months and then backed to baseline body weight at 18 months (78.2 ± 18.0 kg vs. 78.0 ± 17.8, p value = 0.324). The incidence of adverse drug reactions of special interest (polyuria, volume depletion-related events, urinary tract infection, genital infection, and hypoglycemia) was 2.1, 1.6, 2.1, 2.6, and 7.9%, respectively.DiscussionThis real-world study confirmed long-term durability of glycemic control with SGLT2i in not only monotherapy, but also add-on studies with other oral anti-diabetic drugs and/or insulin treatment. However, weight loss became evident early after 6 weeks then reached slightly rebounds after 24 weeks until the end of follow-up. Further studies should be done towards a better understanding of treatment with SGLT2i in routine clinical practice.

Despite the wide use of ziconotide in the USA for treating refractory cancer- and noncancer-related pain, this agent is little used in Europe, even if licensed by the European Medicines Agency (EMA). The reason could be attributed to the high, fixed starting dose required for ziconotide, as stated in the EMA Summary of Product Characteristics (SmPC). This dosage recommendation is based on the results of pivotal clinical studies of ziconotide, which utilized aggressive titration schedules. Thus, a reappraisal of the available evidence, as well as a reflection on real-life clinical experiences, might be useful to identify practice adjustments to improve the clinical application of ziconotide in the European scenario. In line with this need, this paper reports some clinical experiences of patients with chronic pain treated with ziconotide intrathecal (IT) therapy in Italy, particularly focusing on long-term treatment to further characterize and improve the use of this agent in real practice. Moreover, a literature review of the available data on the effectiveness and safety of IT ziconotide is provided. Collected clinical experiences suggested that the use of IT ziconotide represents a valuable option, particularly in cases where other treatments have been ineffective or poorly tolerated. Ziconotide was shown to not cause severe side effects in the long-term treatment, leading to a constant pain relief effect at stable doses, without adverse events that caused therapy interruption. The overall constant ziconotide dosages also suggest the absence of a tolerance effect. In parallel, the evidence in the literature aligns with real-world evidence and further supports the use of IT ziconotide as an important option for the management of chronic pain. IT ziconotide represents a valuable addition to the armamentarium of pain management strategies, offering hope for improved quality of life for patients suffering from chronic, treatment-resistant pain. Continued research and clinical experience will further elucidate its optimal use and role in comprehensive pain care.

Background The use of patient-centric monitoring modalities for assessing therapies, such as vedolizumab (VDZ), are of growing interest to optimize disease outcomes in patients (pts) with Crohn’s disease (CD). Transmural healing is an emerging outcome assessed by intestinal ultrasonography (IUS), which allows frequent evaluation of CD.1,2 Real-world evidence on the effectiveness of current treatments to induce and maintain transmural response to inform treatment decisions is limited. The SUNRISE study aims to describe pts with CD treated with VDZ achieving a composite outcome of complete remission, and transmural response, utilizing IUS. Methods SUNRISE is an ongoing observational, prospective study (NCT05192863) being conducted across 10 sites in Canada, Israel and Italy. Adults with moderately to severely active CD, with a bowel wall thickness of >3 mm based on IUS, and who newly initiated intravenous VDZ are eligible. Complete remission (defined as a composite endpoint of clinically corticosteroid-free [Harvey–Bradshaw Index score of <5 points and no concomitant corticosteroids], biochemical [C-reactive protein and faecal calprotectin normalization] and transmural remission [assessed by IUS]), and transmural response after VDZ treatment are reported after induction with VDZ (Weeks 10/14) and every 6 months until Month 18 or early discontinuation. Methodological details are shown in the Figure. Results This interim analysis included 70 pts; median (interquartile range [IQR]) age was 50.0 (39.0–67.0) years, time since CD diagnosis was 4.0 (0.9–17.2) years and treatment duration (n=69) was 5.0 (3.2–6.1) months. At Month 6, the proportion of pts achieving complete remission, and transmural remission and response were 3/11 (27.3%), 9/28 (32.1%) and 12/28 (42.9%) pts, respectively; data at Weeks 10/14 are shown in the Table. Median (IQR) Short Inflammatory Bowel Disease Questionnaire total score was 4.3 (3.7–5.6) at baseline, 4.5 (3.4–5.3) at Week 10, 4.7 (3.9–5.6) at Week 14 and 5.0 (4.4–6.1) at Month 6. At Month 6, 10/21 pts (47.6%) ranked IUS as their preferred test over colonoscopy, magnetic resonance elastography and computed tomography enterography. Of 40 pts with available data at Month 6, 6 (15.0%) discontinued treatment, 5 (12.5%) switched to subcutaneous VDZ and 1 (2.5%) skipped ≥1 dose of VDZ. During the observation period, 2/70 pts (2.9%) had a CD-related hospitalization, and 1/70 pt (1.4%) each had a CD-related emergency room visit or CD-related surgery (fistula removal). Conclusion The SUNRISE study provides real-world evidence for the use of VDZ to achieve transmural healing in pts with CD and supports pt preference for IUS over other monitoring modalities. Additional follow-up data are required to confirm these findings.

5053 Background: Androgen receptor (AR) antagonists such as enzalutamide (enza) are standard therapy for mCRPC. AR alterations such as amplification (amp) and ligand binding domain (LBD) point mutations (PMs) can cause resistance to hormonal therapies such as enza. The most prevalent AR PMs are T878A and L702H. Preclinical evidence suggests that AR T878A retains sensitivity to enza compared to AR L702H which confers resistance by increasing activation by glucocorticoids. Clinical data evaluating the efficacy of enza in patients with these AR PMs is limited. Here, we analyzed real world data from patients with AR T878A compared to AR L702H, AR amp, or no detected AR mutations ( AR no alt), as identified by circulating tumor DNA (ctDNA), to assess enza efficacy in patients with AR T878A versus AR L702H. Methods: We used GuardantINFORM, a real-world database that combines genomic data from deidentified patients tested via ctDNA with clinical data taken from commercial-payer health claims. Adult mCRPC patients treated with enza who had baseline ctDNA testing and at least 2 claims post ctDNA testing were included. Patients with ≥2 AR PMs were excluded. Matched cohorts were used to assess real-world overall survival (rwOS), time to treatment discontinuation (rwTTD), and time to next treatment (rwTTNT). Propensity score matching was conducted using age and NCI comorbidity index, race, ethnicity, testing location, and enzalutamide line-of-therapy, and was evaluated using Wilcoxon tests. Results: 1,316 mCRPC patients met inclusion criteria. 59 had AR T878A, 56 had AR L702H, 231 had AR amp, and 970 had AR no alt. T878A was compared to L702H, amp, and no alt. Patients with T878A demonstrated significantly improved rwTTD (median 8.0 vs 3.5 mo, P =0.001) and rwTTNT (median 15.8 vs 4.3 mo, P =0.003), but not significantly different rwOS (19.1 vs 13.6 mo, P =0.066) relative to L702H. Patients with T878A demonstrated significantly improved rwTTD (7.7 vs 4.8 mo, P =0.022), but not statistically improved rwTTNT (10.4 vs 6.4 mo, P =0.059) or rwOS (20.2 vs 14.9 mo, P =0.14) relative to AR amp. Patients with T878A demonstrated significantly shorter rwOS (median 19.2 vs 43.6 mo, P =0.03), but no difference in rwTTD (7.7 vs 7.8 mo, P =0.88) or rwTTNT (10.4 vs 14.4 mo, P =0.423) relative to AR no alt. Conclusions: To our knowledge, this is the largest study assessing outcomes of mCRPC patients with AR PMs subsequently treated with enza. Using real-world evidence, we show that AR T878A patients have longer time on therapy with enza relative to patients with AR L702H. rwOS following enza was numerically longer for T878A versus L702H. These findings suggests that AR T878A is relatively more sensitive to enza compared to other resistance mutations. Future work in larger prospective cohorts comparing hormonal treatments in AR -altered patients will help confirm the clinical significance of different AR alterations.

ABSTRACTOutcomes research studies use clinical and administrative data generated in the course of patient care or from patient surveys to examine the effectiveness of treatments. Health care providers need to understand the limitations and strengths of the real-world data sources used in outcomes studies to meaningfully use the results. This paper describes five types of databases commonly used in the United States for outcomes research studies, discusses their strengths and limitations, and provides examples of each within the context of pain treatment. The databases specifically discussed are generated from (1) electronic medical records, which are created from patient-provider interactions; (2) administrative claims, which are generated from providers’ and patients’ transactions with payers; (3) integrated health systems, which are generated by systems that provide both clinical care and insurance benefits and typically represent a combination of electronic medical record and claims data; (4) national surveys, which provide patient-reported responses about their health and behaviors; and (5) patient registries, which are developed to track patients with a given disease or exposure over time for specified purposes, such as population management, safety monitoring, or research.

Osilodrostat is a potent oral steroidogenesis inhibitor that has emerged as the new medical agent for patients with Cushing’s disease (CD) requiring long-term medical therapy for hypercortisolemia control. Its efficacy and safety have been assessed in clinical trials; however, real-world evidence is still scarce. This study aimed to investigate the long-term treatment (156 weeks) clinical and biochemical effect of osilodrostat in six patients with CD at a single center in Poland, initially participating in the LINC4 study. At week 36, all six patients met the key secondary endpoint of the LINC4 trial, achieving normalization of median urinary free cortisol. Osilodrostat treatment allowed for complete disease control in all patients and none of the patients was excluded due to the lack of treatment effectiveness in 156 weeks of follow-up. All patients demonstrated significant improvement from baseline on most metabolic and cardiovascular parameters, which was most evident at week 36 and sustained throughout the study period. This study supports and strengthens the role of osilodrostat as an effective long-term medical treatment in patients with CD. We also present three patient case histories in detail to highlight the clinical situations that endocrinologists might face during osilodrostat therapy.