scholarly journals Do we really know how many clinical trials are conducted ethically? Why research ethics committee review practices need to be strengthened and initial steps we could take to strengthen them

2020 ◽  
pp. medethics-2019-106014 ◽  
Author(s):  
Mark Yarborough
Keyword(s):  
Clinical Trials ◽  
Research Ethics ◽  
Early Phase ◽  
Ethics Committees ◽  
Social Value ◽  
Know How ◽  
Early Phase Trials ◽  
Potential Benefits ◽  
Later Phase ◽  
Requisite Amount

Research Ethics Committees (RECs) play a critical gatekeeping role in clinical trials. This role is meant to ensure that only those trials that meet certain ethical thresholds proceed through their gate. Two of these thresholds are that the potential benefits of trials are reasonable in relation to risks and that trials are capable of producing a requisite amount of social value. While one ought not expect perfect execution by RECs of their gatekeeping role, one should expect routine success in it. This article reviews a range of evidence showing that substantial numbers of ethically tainted trials are receiving REC approvals. Many of the trials are early phase trials that evidence shows have benefits that may not be reasonable compared with their risks and many others are later trials that evidence shows may lack sufficient social value. The evidence pertains to such matters as methodologically inadequate preclinical studies incapable of supporting the inferences that REC members must make about the prospects for potential benefit needed to offset the risks in early phase trials and sponsorship bias that can cause improperly designed, conducted, analysed and reported later phase trials. The analysis of the evidence makes clear that REC practices need to be strengthened if they are to adequately fulfil their gatekeeping role. The article also explores options that RECs could use in order to improve their gatekeeping function.

Understanding patient expectations in early-phase clinical trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6543-6543
Author(s):  
K. P. Weinfurt ◽  
D. M. Seils ◽  
J. P. Tzeng ◽  
K. L. Compton ◽  
D. P. Sulmasy ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Early Phase ◽  
Positive Attitude ◽  
Phase 1 ◽  
Experimental Therapy ◽  
High Expectations ◽  
Early Phase Trials ◽  
Semistructured Interviews ◽  
Two Factors ◽  
Early Phase Clinical Trials

6543 Background: Participants in early-phase clinical trials have reported high expectations of benefit from their participation. There is concern that participants misunderstand the trials to which they have consented. Such concerns are based on assumptions about what patients mean when they respond to questions about likelihood of benefit. In this study, we explored some of these assumptions. Methods: Participants were 27 women and 18 men in phase 1 or 2 oncology trials and randomized to 1 of 3 interview protocols corresponding to 3 target questions about likelihood of benefit: frequency-type (‘Out of 100 patients who participate in this study, how many do you expect will have their cancer controlled as a result of the experimental therapy?‘); belief-type (‘How confident are you that the experimental therapy will control your cancer?‘); and vague (‘What is the chance that the experimental therapy will control cancer?‘). In semistructured interviews, we queried participants about how they understood and answered the target question. Each participant then answered and discussed one of the other target questions. Results: Participants tended to provide higher expectations in response to the belief-type question (median, 80) than in response to the frequency-type or vague questions (medians, 50) (P=.02). Only 7 (16%) participants said their answers were based on what they were told during the consent process. The most common justifications for responses involved positive attitude (n=27 [60%]) and references to physical health (n=23 [51%]). References to positive attitude were most common among participants with high (>70%) expectations of benefit (n=11 [85%]) and least common among those with low (<50%) expectations of benefit (n=3 [27%]) (P=.04). Conclusions: We identified two factors that should be considered when determining whether high expectations of benefit are signs of misunderstanding. First, participants report different expectations of benefit depending on how the question is asked. Second, the justifications participants give for their answers suggest that many participants use their responses to express hope rather than to describe their understanding of the clinical trial. These findings should inform methods for evaluating the quality of informed consent in early-phase trials. No significant financial relationships to disclose.

Implementation of the EU clinical trial regulation transforms the ethics committee systems and endangers ethical standards

2020 ◽  
pp. medethics-2020-106757
Author(s):  
Vilma Lukaseviciene ◽  
Joerg Hasford ◽  
Dirk Lanzerath ◽  
Eugenijus Gefenas
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Research Ethics ◽  
Ethics Committees ◽  
Ethics Committee ◽  
Negative Consequences ◽  
Ethics Review ◽  
Clinical Trial Directive ◽  
Favourable Environment ◽  
The Eu

The upcoming Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use (Regulation), which will replace the current Clinical Trial Directive at the end of 2021, has triggered a significant reform of research ethics committee systems in Europe. Changes related to ethics review of clinical trials in the EU were considered to be essential to create a more favourable environment to conduct clinical trials in the EU. The concern is, however, that the role of the research ethics committees will weaken in at least some of the Member States because the new Regulation allows narrowing down the scope of ethics review as compared with the currently valid Clinical Trial Directive. Although the new Regulation may lead to faster approval procedures for clinical trials, which is especially relevant in the context of pandemics, high-quality ethics reviews integrating methodological aspects of a clinical trial should nevertheless be ensured. To maintain high research ethics standards as well as to foster measures to mitigate potential negative consequences of the reform, it is therefore of vital importance to start debating and sharing the reflections about the potential consequences of these transformations and trends as soon as possible.

scholarly journals Experiences of establishing an academic early phase clinical trials unit

2017 ◽  
Vol 14 (4) ◽  
pp. 349-356 ◽  
Author(s):  
Sarah R Brown ◽  
Debbie Sherratt ◽  
Gill Booth ◽  
Julia Brown ◽  
Fiona Collinson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Early Phase ◽  
Late Phase ◽  
Knowledge Retention ◽  
Lessons Learned ◽  
Phase Iii ◽  
Trial Management ◽  
Early Phase Trials ◽  
Early Phase Trial ◽  
Phase Trial

Background: Early phase trials are essential in drug development, determining appropriate dose levels and assessing preliminary activity. These trials are undertaken by industry and academia, with increasing collaborations between the two. There is pressure to perform these trials quickly, safely, and robustly. However, there are inherent differences between developing and managing early phase, compared to late phase, drug trials. This article describes an approach to establishing an academically led early phase trial portfolio, highlighting lessons learned and sharing experiences. Methods: In 2009, the University of Leeds Clinical Trials Research Unit became the Clinical Trials Coordinating Office for Myeloma UK’s phase I and II trials. We embarked on a transition from working extensively in phase III to early phase trials development and conduct. This involved evaluating and revising our well-established standard operating procedures, visiting other academic early phase units, and developing essential new documentation and processes. Results: A core team of trial and data managers and statisticians was established to facilitate expertise and knowledge retention. A detailed training plan was implemented focussing on essential standard practices for early phase. These included pharmacovigilance, recruitment, trial design and set-up, data and site monitoring, and oversight committees. Training in statistical methods for early phase trials was incorporated. Conclusion: Initial scoping of early phase trial management and conduct was essential in establishing this early phase portfolio. Many of the processes developed were successful. However, regular review and evaluation were implemented to enable changes and ensure efficiencies. It is recommended that others embarking on this venture build on the experiences described in this article.

scholarly journals Early-Phase Clinical Trials In The Community: Results From the National Cancer Institute Community Cancer Centers Program Early-Phase Working Group Baseline Assessment

2013 ◽  
Vol 9 (2) ◽  
pp. e55-e61 ◽  
Author(s):  
Howard A. Zaren ◽  
Suresh Nair ◽  
Ronald S. Go ◽  
Rebecca A. Enos ◽  
Keith S. Lanier ◽  
...  
Keyword(s):  
Clinical Trials ◽  
National Cancer Institute ◽  
Early Phase ◽  
Working Group ◽  
Baseline Assessment ◽  
Cancer Centers ◽  
Early Phase Trials ◽  
Critical Components ◽  
Early Phase Clinical Trials

The authors conclude that community cancer centers are capable of conducting early-phase trials; infrastructure and collaborations are critical components of success.

scholarly journals Level of Evidence for FDA Drug Approvals in Pivotal Clinical Trials of Hematological Malignancies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Samer Al Hadidi ◽  
Carlos A. Ramos
Keyword(s):  
Clinical Trials ◽  
Early Phase ◽  
Hematological Malignancies ◽  
Phase Iii ◽  
Clinical Activity ◽  
Level Of Evidence ◽  
Phase Iii Clinical Trials ◽  
Early Phase Trials ◽  
Phase Iii Trials ◽  
Drug Approvals

BACKGROUND Clinical trials are integral to improve treatment outcomes for patients with hematological malignancies. Although early phase (I/II) clinical trials may provide evidence of clinical efficacy, the main goal for early phase trials is to assess safety signal. Results of phase III clinical trials provide the strongest evidence to support the use of new cancer medications. The Food and Drug Administration (FDA) is responsible to ensure appropriate control and supervision of pharmaceutical drugs. METHODS On the basis of publicly available study protocols and FDA reviews, the authors reviewed the level of evidence in 52 clinical trials supporting 49 drug approvals from 2016 to 2020. Data cut point was May 2020. These trials resulted in approval of medications to treat leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, myelodysplastic syndrome, myeloproliferative neoplasms and multiple myeloma. RESULTS A total of 52 clinical trials were assessed in the 5 years period. Phase III trials supported 61.5% while earlier phase trials supported 36.5% of subsequent FDA hematological malignancies approvals. The level of evidence to support FDA approvals improved with time with 50% of approvals in 2016 and 2017 supported by phase III clinical trials compared to 69% in 2019. Approvals were based on early phase trials in mantle cell lymphoma (100%), chronic myeloid leukemia (100%), diffuse large B cell lymphoma (100%), classic Hodgkin's lymphoma (67%) and acute myeloid leukemia (56%). Phase III trials enrolled 87% of the patients (14238 from16429 patients). Eighteen drug approvals (37% of all approvals) were based on 13% of the total number of patients in the studied period. CONCLUSIONS Level of evidence to support drug approvals in hematological malignancies was based on early phase trials in more than a third of the times. Although early phase studies are appropriate for safety signals, further clinical activity assessment should be done to support the use of new drugs to treat hematological malignancies. Previous successful early phase studies failed to show clinical activity in phase III studies. Despite the fact that use of new approved drugs based on early phase studies evidence may be needed, patients and healthcare providers should be aware of such possibility when using newly approved medications. Figure Disclosures Ramos: Novartis: Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding; Kuur Therapeutics: Research Funding.

scholarly journals Access to early phase clinical trials for children with relapsed and refractory neuroblastoma. A multicentre international study.

2021 ◽  
Author(s):  
Marta Cortes ◽  
Fernando Carceller ◽  
Alba Rubio-San-Simon ◽  
Sucheta Vaidya ◽  
Francisco Bautista ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Early Phase ◽  
Performance Status ◽  
International Study ◽  
Eligibility Criteria ◽  
Early Phase Trials ◽  
Novel Drugs ◽  
Innovative Therapies ◽  
Early Phase Clinical Trials ◽  
Relapsed Disease

Objectives. Neuroblastoma is the most common extracranial tumour in children, and prognosis for refractory and relapsed disease is still poor. Early Phase clinical trials play a pivotal role in the development of novel drugs. Ensuring adequate recruitment is crucial. The primary aim was to determine the rate of participation trials for children with refractory/relapsed neuroblastoma in two of the largest Drug Development European institutions. Methods. Data from patients diagnosed with refractory/relapsed neuroblastoma between January 2012 and December 2018 at the two institutions were collected and analysed. Results. Overall, 48 patients were included. A total of 31 (65%) refractory/relapsed cases were enrolled in early Phase trials. The main reasons for not participating in clinical trials included: not fulfilling eligibility criteria prior to consent (12/17, 70%) and screening failure (2/17, 12%). Median time on trial was 4.3 months (range 0.6-13.4). Most common cause for trial discontinuation was disease progression (67.7%). Median overall survival was longer in refractory (28 months, 95% CI, 20.9-40.2) than in relapsed patients (14 months, 95% CI, 8.1-20.1)) [p=0,034]. Conclusions. Although two thirds of children with refractory/relapsed neuroblastoma were enrolled in early Phase trials, recruitment rates can still be improved. The main cause for not participating on trials was not fulfilling eligibility criteria prior to consent, mainly due to performance status and short life expectancy. This study highlights the hurdles to access to innovative therapies for children with relapsed/refractory neuroblastomas and identifies key areas of development to improve recruitment to early phase trials.

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