Challenges and practical realities of long‐term patient follow‐up in three xeno‐islet clinical trials: The experience in pig islet xenotransplantation trials in New Zealand and Argentina

2020 ◽  
Vol 27 (3) ◽  
Author(s):  
Shaun Wynyard
2021 ◽  
pp. 135245852110002
Author(s):  
Bruce AC Cree ◽  
Jeffrey A Cohen ◽  
Anthony T Reder ◽  
Davorka Tomic ◽  
Diego Silva ◽  
...  

Background: Disease-modifying therapies (DMTs) can reduce the risk of disability worsening in patients with relapsing forms of multiple sclerosis (RMS). High-efficacy DMTs can lead to confirmed or sustained disability improvement (CDI and SDI). Objective and Methods: Post hoc analyses of data from the TRANSFORMS, FREEDOMS, and FREEDOMS II trials and their extensions assessed the effects of fingolimod (0.5–1.25 mg/day) on stabilizing or improving disability over ⩽8 years in participants with RMS. CDI and SDI rates were compared between participants initially randomized to fingolimod, interferon (IFNβ-1a), or placebo. Results: At 8 years’ follow-up in TRANSFORMS, 35.1% (95% confidence interval [CI], 28.2%–43.1%) of assessed participants in the IFNβ-1a–fingolimod switch group and 41.9% (36.6%–47.6%) on continuous fingolimod experienced CDI; disability did not worsen in approximately 70%. Similar results were seen in the combined FREEDOMS population. Proportionally fewer TRANSFORMS participants achieved SDI in the IFNβ-1a–fingolimod switch group than on continuous fingolimod (5.4% [3.0%–9.5%] vs 14.2% [10.8%–18.4%], p = 0.01). Conclusion: CDI and SDI are outcomes of interest for clinical trials and for long-term follow-up of participants with RMS. Monitoring CDI and SDI in addition to disability worsening may facilitate understanding of the therapeutic benefit of RMS treatments.


2006 ◽  
Vol 14 (2) ◽  
pp. 169-180 ◽  
Author(s):  
Frances V. Wilder ◽  
John P. Barrett ◽  
Edward J. Farina

The value of exercise for people with knee osteoarthritis (OA) receives continuing consideration. The optimal length of study follow-up time remains unclear. A group of individuals with knee OA participating in an exercise intervention was followed for 2 years. The authors quantified the change in knee-pain scores during Months 1–12 and during Months 13–24. Eleven individuals with radiographic knee OA and knee-pain scores of 2+ were evaluated. Pain scores were collected weekly from participants who exercised three times a week. Participants demonstrated pain reduction during both time periods. Pain reduction during Months 13–24, –10.7%, was slightly higher than pain reduction during Months 1–12, –7.8%. Among people with knee OA who exercise, these findings suggest that knee-pain amelioration continues beyond 12 months. Clinicians should consider encouraging long-term exercise programs for knee-OA patients. To best characterize the effect of exercise on knee pain, researchers designing clinical trials might want to lengthen the studies’ duration.


2019 ◽  
Vol 46 (3) ◽  
pp. 183-187 ◽  
Author(s):  
Bryan Cwik

Design of clinical trials for germline gene editing stretches current accepted standards for human subjects research. Among the challenges involved is a set of issues concerning intergenerational monitoring—long-term follow-up study of subjects and their descendants. Because changes made at the germline would be heritable, germline gene editing could have adverse effects on individuals’ health that can be passed on to future generations. Determining whether germline gene editing is safe and effective for clinical use thus may require intergenerational monitoring. The aim of this paper is to identify and argue for the significance of a set of ethical issues raised by intergenerational monitoring in future clinical trials of germline gene editing. Though long-term, multigenerational follow-up study of this kind is not without precedent, intergenerational monitoring in this context raises unique ethical challenges, challenges that go beyond existing protocols and standards for human subjects research. These challenges will need to be addressed if clinical trials of germline gene editing are ever pursued.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Cristín Ryan ◽  
Ruth Teh ◽  
Simon Moyes ◽  
Tim Wilkinson ◽  
Martin Connolly ◽  
...  

Abstract Background Prescribing for older people is complex, and many studies have highlighted that appropriate prescribing in this cohort is not always achieved. However, the long-term effect of inappropriate prescribing on outcomes such as hospitalisation and mortality has not been demonstrated. The aim of this study was to determine the level of potentially inappropriate prescribing (PIP) for participants of the Life and Living in Advanced Age: A Cohort Study in New Zealand (LiLACS NZ) study at baseline and examine the association between PIP and hospitalisation and mortality at 12-months follow-up. Methods PIP was determined using STOPP/START. STOPP identified potentially inappropriate medicines (PIMs) prescribed, START identified potential prescribing omissions (PPOs). STOPP/START were applied to all LiLACS NZ study participants, a longitudinal study of ageing, which includes 421 Māori aged 80–90 years and 516 non-Māori aged 85 years. Participants’ details (e.g. age, sex, living arrangements, socioeconomic status, physical functioning, medical conditions) were gathered by trained interviewers. Some participants completed a core questionnaire only, which did not include medications details. Medical conditions were established from a combination of self-report, review of hospital discharge and general practitioner records. Binary logistic regression, controlled for multiple potential confounders, was conducted to determine if either PIMs or PPOs were associated with hospital admissions and mortality (p < 0.05 was considered significant). Results Full data were obtained for 267 Māori and 404 non-Māori. The mean age for Māori was 82.3(±2.6) years, and 84.6(±0.53) years for non-Māori. 247 potentially inappropriate medicines were identified, affecting 24.3% Māori and 28.0% non-Māori. PIMs were not associated with 12-month mortality or hospitalisation for either cohort (p > 0.05; adjusted models). 590 potential prescribing omissions were identified, affecting 58.1% Māori and 49.0% non-Māori. PPOs were associated with hospitalisation (p = 0.001 for Māori), but were not associated with risk of mortality (p > 0.05) for either cohort within the 12-month follow-up (adjusted models). Conclusion PPOs were more common than PIMs and were associated with an increased risk of hospitalisation for Māori. This study highlights the importance of carefully considering all indicated medicines when deciding what to prescribe. Further follow-up is necessary to determine the long-term effects of PIP on mortality and hospitalisation.


Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Thomas Salaets ◽  
Emilie Lavrysen ◽  
Anne Smits ◽  
Sophie Vanhaesebrouck ◽  
Maissa Rayyan ◽  
...  

Abstract Background Although recruiting newborns is ethically challenging, clinical trials remain essential to improve neonatal care. There is a lack of empirical data on the parental perspectives following participation of their neonate in a clinical trial, especially at long term. The objective of this study is to assess experiences and emotions of parents, long term after trial participation in an interventional drug trial. Methods Parents of former participants of five neonatal interventional drug trials were surveyed at long term (3–13 years ago) after participation. The survey assessed parental contentment with trial participation, perceived influence of the trial on care and health, emotional consequences of participation, and awareness of typical clinical trial characteristics on 6-point Likert scales. Results Complete responses were received from 123 parents (52% of involved families). Twenty percent of parents did not remember participation. Those who remembered participation reported high contentment with overall trial participation (median 5.00), but not with follow-up (median 3.00). Most parents did not perceive any influence of the trial on care (median 2.00) and health (median 2.43). Almost all parents reported satisfaction and pride (median 4.40), while a minority of parents reported anxiety and stress (median 1.44) or guilt (median 1.33) related to trial participation. A relevant minority was unaware of typical trial characteristics (median 4.20; 27% being unaware). Conclusions Overall, parents reported positive experiences and little emotional distress long term after participation. Future efforts to improve the practice of neonatal clinical trials should focus on ensuring effective communication about the concept and characteristics of a clinical trial during consent discussions and on the follow-up after the trial.


JAMA ◽  
2020 ◽  
Vol 324 (4) ◽  
pp. 369 ◽  
Author(s):  
Rowan T. Chlebowski ◽  
Garnet L. Anderson ◽  
Aaron K. Aragaki ◽  
JoAnn E. Manson ◽  
Marcia L. Stefanick ◽  
...  

2016 ◽  
Vol 67 (5) ◽  
pp. 600
Author(s):  
William J. Kostis ◽  
Abel E. Moreyra ◽  
Javier Cabrera ◽  
John B. Kostis

Author(s):  
THIAGO BEZERRA MORAIS ◽  
DANIELA FRANCESCATO VEIGA ◽  
MIGUEL SABINO NETO ◽  
LYDIA MASAKO FERREIRA

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 132-132
Author(s):  
Justin M Watts ◽  
Lynette Zickl ◽  
Mark R Litzow ◽  
Selina M Luger ◽  
Hillard M Lazarus ◽  
...  

Abstract Abstract 132 Late relapse in acute myeloid leukemia (AML) has been infrequently studied and variably defined in the literature. Two series have shown that late relapse of AML ≥5 years after first complete remission (CR1) is uncommon, with rates of 1.19–3% (Medeiros et al, Leuk Lymphoma 2007; Verma et al, Leuk Lymphoma 2010). We searched the long-term data available on 784 adults (<60 years-old) who were treated on 1 of 4 ECOG clinical trials (E3483, PC486, E3489, or E1900) and achieved CR1 for reports of late relapse (defined as recurrence of AML ≥3 years after CR1). Median follow-up for the 553 patients last known alive was 11.1 years. The longest median follow-up was 17.2 years on trial PC486. Outcomes We found that 11 patients (1.4%) relapsed late; of these, 2 were treated on E3483, 1 on PC486, 5 on E3489, and 3 on E1900. Seven patients with late relapse died from their disease and 4 were living at last known follow-up. Only 1 patient (0.13%) had recurrence of AML ≥5 years after achieving CR1. It is possible that more late relapses will occur on E1900 (a more recent study with ongoing follow-up). All of these trials except E3483 treated some patients with autologous hematopoietic cell transplantation (autoHCT) as part of post remission therapy. On PC486, no post remission consolidation chemotherapy was administered before autoHCT. Ninety-eight total patients on E3489 and PC486 received autoHCT, and there were no late relapses; on E1900, 2 of the 141 patients treated with autoHCT developed late relapse. No patients who underwent allogeneic (allo) HCT in CR1 experienced late relapse on any of the 4 clinical trials. Nine of the 11 patients with late relapse did not undergo HCT; of these, 5 were consolidated with high-dose cytarabine, 2 received maintenance with low-dose cytarabine and 6-thioguanine, and 2 received unknown post remission therapy. Of the 3 patients with late relapse on E1900, 2 received standard-dose and 1 high-dose daunorubicin with induction. Conclusions Across all 4 trials, only 2 of the 239 patients (0.8%) treated with post remission autoHCT experienced late relapse of AML (≥3 years after CR1), which reinforces previously published data that late relapse after autoHCT is uncommon (Cassileth et al, J Clin Oncol 1993). Furthermore, of the 35 patients treated with autoHCT on PC486, 11 relapsed early and no patients relapsed late, suggesting that post remission chemotherapy may not be necessary before autoHCT. Based on this large AML cohort of nearly 800 patients with long-term follow-up, patients who remain in CCR for at least 3 years have a very low risk of relapse and can be considered cured of their disease. Moreover, given that recurrent AML was extremely rare after 5 years or more of CCR (<0.2%), the risk of therapy-related AML from contemporary induction and post remission strategies including HCT appears to be minimal. Disclosures: No relevant conflicts of interest to declare.


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