ERANET JTC 2011: Submission and Activation of an International Academic Translational Project in Advanced Breast Cancer. Experience From the ET-FES Study

Background: Academic research is important to face unmet medical needs. The Oncological community encounters many hurdles in setting up multicenter investigator-driven trials mainly due to administrative complexity. The purpose of a network organization at a multinational level is to facilitate clinical trials through standardization, coordination, and education for drug development and regulatory approval.Methods: The application of an European grant foresees the creation of a consortium which aims at facilitating multi-center academic clinical trials.Results: The ERA-NET TRANSCAN Call 2011 on “Validation of biomarkers for personalized cancer medicine” was released on December 2011. This project included Italian, Spanish, French and German centers. The approval process included Consortium constitution, project submission, Clinical Trial Submission, and activation on a national level. The different timescales for submitting study documents in each Country and the misalignment of objections by each Competent Authority CA, generated several requests for changes to the study documents which meant amendments had to be made; as requested by the 2001/20/EC Directive, the alignment of core documents is mandatory. This procedure impacted significantly on study activation timelines. Time to first patient in was 14, 10, 28, and 31 months from the date of submission in Italy, France, Spain, and Germany, respectively. Accrual was stopped on 22nd January 2021 due to an 18F FES shortage as the primary reason but also for having exceeded the project deadlines with consequent exhaustion of the funds allocated for the project.Conclusions: Pharmaceutical companies might be reluctant to fund research projects aimed at treatment individualization if the approval for a wider indication has already been achieved. Academic trials therefore become fundamental for promoting trials which are not attractive to big pharma. It was very difficult and time consuming to activate an academic clinical trial, for this reason, a study may become “old” as new drugs entered into the market. National institutions should promote the development of clinical research infrastructures and network with competence in regulatory, ethical, and legal skills to speed up academic research.

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Practical and conceptual issues of clinical trial registration for Brazilian researchers

Sao Paulo Medical Journal ◽

10.1590/1516-3180.2014.00441803 ◽

2015 ◽

Vol 134 (1) ◽

pp. 28-33 ◽

Cited By ~ 3

Author(s):

Carolina Gomes Freitas ◽

Thomas Fernando Coelho Pesavento ◽

Maurício Reis Pedrosa ◽

Rachel Riera ◽

Maria Regina Torloni

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

International Committee ◽

New Drugs ◽

Trial Registration ◽

Clinical Trial Registry ◽

Clinical Trial Registration ◽

Registration Process ◽

Trial History ◽

Definition Of

CONTEXT AND OBJECTIVE: Clinical trial registration is a prerequisite for publication in respected scientific journals. Recent Brazilian regulations also require registration of some clinical trials in the Brazilian Clinical Trials Registry (ReBEC) but there is little information available about practical issues involved in the registration process. This article discusses the importance of clinical trial registration and the practical issues involved in this process. DESIGN AND SETTING: Descriptive study conducted by researchers within a postgraduate program at a public university in São Paulo, Brazil. METHODS: Information was obtained from clinical trial registry platforms, article reference lists and websites (last search: September 2014) on the following topics: definition of a clinical trial, history, purpose and importance of registry platforms, the information that should be registered and the registration process. RESULTS: Clinical trial registration aims to avoid publication bias and is required by Brazilian journals indexed in LILACS and SciELO and by journals affiliated to the International Committee of Medical Journal Editors (ICMJE). Recent Brazilian regulations require that all clinical trials (phases I to IV) involving new drugs to be marketed in this country must be registered in ReBEC. The pros and cons of using different clinical trial registration platforms are discussed. CONCLUSIONS: Clinical trial registration is important and various mechanisms to enforce its implementation now exist. Researchers should take into account national regulations and publication requirements when choosing the platform on which they will register their trial.

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Canadian Recommendations for Clinical Trials of Pharmacologic Interventions in Rheumatoid Arthritis: Inclusion Criteria and Study Design: Table 1.

The Journal of Rheumatology ◽

10.3899/jrheum.110188 ◽

2011 ◽

Vol 38 (10) ◽

pp. 2095-2104 ◽

Cited By ~ 8

Author(s):

JACOB KARSH ◽

EDWARD C. KEYSTONE ◽

BOULOS HARAOUI ◽

J. CARTER THORNE ◽

JANET E. POPE ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Trial ◽

Clinical Trials ◽

Disease Activity ◽

Study Design ◽

New Drugs ◽

Nominal Group ◽

Consensus Method ◽

Inclusion Criteria ◽

Design Features

Objective.Current clinical trial designs for pharmacologic interventions in rheumatoid arthritis (RA) do not reflect the innovations in RA diagnosis, treatment, and care in countries where new drugs are most often used. The objective of this project was to recommend revised entry criteria and other study design features for RA clinical trials.Methods.Recommendations were developed using a modified nominal group consensus method. Canadian Rheumatology Research Consortium (CRRC) members were polled to rank the greatest challenges to clinical trial recruitment in their practices. Initial recommendations were developed by an expert panel of rheumatology trialists and other experts. A scoping study methodology was then used to examine the evidence available to support or refute each initial recommendation. The potential influence of CRRC recommendations on primary outcomes in future trials was examined. Recommendations were finalized using a consensus process.Results.Recommendations for clinical trial inclusion criteria addressed measures of disease activity [Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) > 3.2 PLUS ≥ 3 tender joints using 28-joint count (TJC28) PLUS ≥ 3 swollen joint (SJC28) OR C-reactive protein (CRP) or ESR > upper limit of normal PLUS ≥ 3 TJC28 PLUS ≥ 3 SJC28], functional classification, disease classification and duration, and concomitant RA treatments. Additional recommendations regarding study design addressed rescue strategies and longterm extension.Conclusion.There is an urgent need to modify clinical trial inclusion criteria and other study design features to better reflect the current characteristics of people living with RA in the countries where the new drugs will be used.

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Awareness and Opinions of Research Professionals on India's New Drug and Clinical Trials Regulations: Protocol for a Cross-Sectional Web-Based Survey Study

JMIR Research Protocols ◽

10.2196/14744 ◽

2020 ◽

Vol 9 (1) ◽

pp. e14744

Author(s):

Vishal Vennu ◽

Saurabh Dahiya

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

New Drugs ◽

Survey Study ◽

Multiple Sources ◽

Cross Sectional ◽

Web Based ◽

Google Docs ◽

New Drug ◽

Research Professionals

Background Although several studies have been conducted and several articles have been published on India's new clinical trial regulations, very few have examined the views of investigators and ethics board members regarding modifications to the previous regulations. Overall, they have neglected to find out the opinions of other relevant professionals, such as research assistants, coordinators, associates, and managers. To our knowledge, no study has yet investigated the awareness and opinions of Indian research professionals on the new 2019 regulations. Objective This study aims to describe the awareness and opinions of Indian research professionals on the new drug and clinical trial regulations. Methods In this cross-sectional, Web-based study, we will conduct an open survey for various Indian research professionals. These professionals will be selected randomly using multiple sources. The survey questionnaires, which have already been validated, were developed using the form function in Google docs. A Web link was generated for participants to take the survey. Descriptive statistics will be shown as means and standard deviations for constant variables, whereas certain variables will instead be shown as numbers and percentages. Results The survey was opened in July 2019. Enrollment has already started and will be completed in three months. The results calculations are expected to begin in October 2019. Conclusions The results of the survey are expected to represent the views of research professionals on the new regulations that will support the development of clinical research and the pharmaceutical industry in India. These regulations are expected to help advance clinical trials, help with the approval of new drugs, and enhance ethical norms in the country. International Registered Report Identifier (IRRID) PRR1-10.2196/14744

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Clinical Trial Regulations In India : Past, Present and Future

JMS SKIMS ◽

10.33883/jms.v20i1.305 ◽

2017 ◽

Vol 20 (1) ◽

pp. 5-17

Author(s):

Haroon Rashid

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Disease Burden ◽

International Standards ◽

New Drugs ◽

Safety And Efficacy ◽

Long Time ◽

Regulatory Bodies ◽

Guidance Documents ◽

Human Use

Clinical trials are the only way of establishing the safety and efficacy of any new drug before its introduction in the market for human use. Clinical trials (with safeguards) are necessary for introduction of new drugs for a country like India, considering its disease burden and emergence of new variants of disease.The regulatory bodies need to frame guidelines and regulatory approval processes on a par with international standards. Many of the new laws, guidance documents, notifications and initiatives for regulating pharmaceutical industry were in the charts for quite a long time. Indian regulatory authorities have started looking into speedy implementation and providing support in terms ofnecessary infrastructure and investment. JMS 2017; 20(1):5-17

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Metastatic colorectal cancer (mCRC) patterns of care: Implications for clinical trial design

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4079 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4079-4079 ◽

Cited By ~ 1

Author(s):

C. S. Denlinger ◽

M. A. Collins ◽

Y. Wong ◽

S. Litwin ◽

N. J. Meropol

Keyword(s):

Clinical Trial ◽

Decision Making ◽

Clinical Trials ◽

Trial Design ◽

Clinical Trial Design ◽

New Drugs ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Treatment Change ◽

Therapy Regimen

4079 Background: New approaches have expanded options for patients (pts) with mCRC. To characterize current practice paradigms that might bear on clinical trial design, we analyzed decision-making and treatment patterns in pts treated at a Comprehensive Cancer Center since the introduction of cetuximab (CET), and bevacizumab (BV). Methods: A retrospective review of all pts diagnosed with mCRC between 3/1/04 and 8/28/06 treated at Fox Chase Cancer Center. Results: 160 pts were treated, with 157 pts receiving at least one therapy regimen by 10 attending oncologists. There were 350 changes in therapy with 246 (70%) including continuation of at least one prior drug (92 BV, 111 fluoropyrimidines, 43 other). The most common reasons for treatment change were toxicity (33%), progressive disease (PD) (29%), treatment breaks (15%), and metastasectomy (11%) ( Table ). PD was a more common cause for treatment discontinuation in later phases of treatment (18% initial regimen vs. 36% subsequent regimens, p=0.0002). 24% of pts treated with oxaliplatin (OX) discontinued due to neuropathy. Hypersensitivity caused discontinuation in 5% of pts with OX and 7% of pts with CET. Resection of metastases was undertaken in 38% of pts. 43% of these pts received neoadjuvant therapy, and 56% received adjuvant therapy. 30% of pts have died, 29% remain on active treatment, 28% are on a treatment break, 3% are on hospice, and 11% are lost to follow-up. Conclusions: PD is no longer the primary reason for change of therapy in pts with mCRC. Metastasectomy is common and OX neuropathy is often treatment-limiting. These findings have important implications for endpoint selection and design of clinical trials in mCRC. Future clinical trials in mCRC must recognize treatment complexities and capture key components of decision-making that may result in prolonged survival. Furthermore, treatment breaks represent a potential window for the evaluation of new drugs. [Table: see text] No significant financial relationships to disclose.

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Awareness and Opinions of Research Professionals on India's New Drug and Clinical Trials Regulations: Protocol for a Cross-Sectional Web-Based Survey Study (Preprint)

10.2196/preprints.14744 ◽

2019 ◽

Author(s):

Vishal Vennu ◽

Saurabh Dahiya

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

New Drugs ◽

Survey Study ◽

Multiple Sources ◽

Cross Sectional ◽

Web Based ◽

Google Docs ◽

New Drug ◽

Research Professionals

BACKGROUND Although several studies have been conducted and several articles have been published on India's new clinical trial regulations, very few have examined the views of investigators and ethics board members regarding modifications to the previous regulations. Overall, they have neglected to find out the opinions of other relevant professionals, such as research assistants, coordinators, associates, and managers. To our knowledge, no study has yet investigated the awareness and opinions of Indian research professionals on the new 2019 regulations. OBJECTIVE This study aims to describe the awareness and opinions of Indian research professionals on the new drug and clinical trial regulations. METHODS In this cross-sectional, Web-based study, we will conduct an open survey for various Indian research professionals. These professionals will be selected randomly using multiple sources. The survey questionnaires, which have already been validated, were developed using the form function in Google docs. A Web link was generated for participants to take the survey. Descriptive statistics will be shown as means and standard deviations for constant variables, whereas certain variables will instead be shown as numbers and percentages. RESULTS The survey was opened in July 2019. Enrollment has already started and will be completed in three months. The results calculations are expected to begin in October 2019. CONCLUSIONS The results of the survey are expected to represent the views of research professionals on the new regulations that will support the development of clinical research and the pharmaceutical industry in India. These regulations are expected to help advance clinical trials, help with the approval of new drugs, and enhance ethical norms in the country. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/14744

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INTELLECTUAL PROPERTY ON DATA OF COVID-19 OFF-LABEL TREATMENT AND DATA OF COMPASSIONATE USE OF MEDICINES AND ACCESS TO TREATMENT IN A PANDEMIC

Theory and Practice of Intellectual Property ◽

10.33731/42020.216948 ◽

2020 ◽

Author(s):

Оксана Кашинцева ◽

Микита Трохименко

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Intellectual Property ◽

Treatment Options ◽

Legal Protection ◽

New Drugs ◽

European Medicines Agency ◽

Compassionate Use ◽

Access To Treatment ◽

Off Label

The article concerns the issues of legal protection of data obtained as a result of off-label drugs therapy of COVID-19 and of data obtained of the compassionate use of medicines in treatment of COVID-19. The authorsargue that neither data on the use of off-label or on the basis of a compassionate use in the treatment of coronavirus (data obtained in solidarity clinical trials) are not determined as the information that should be protected from unfair commercial use.Regarding to the use of off-label for a new purpose of drag it is not be considered as a «new chemical substance», because the drug is already registered, and therefore known, and in the case of obtaining data in compassionate use, this information is removed from the trade secret regime by the WHO and EMA opinion. Such information is opened to use from the beginning. Therefore, in both of the above cases, it could notbe considered as an «unfair use» in the meaning of Art. 39 TRIPS Agreements.The WHO apply to the world community and informed about the «Solidarity» clinical trial for COVID-19 treatments». Solidified clinical trials of COVID-19 treatment compare four treatment options to evaluate their efficacy in COVID-19 therapy. Solidarity-based clinical trials aim to quickly identify which of the drugs tested slows disease progression or improves survival. New drugs can be added to solidarity studiesbased on new data.On April 3, 2020, the Committee for Medicinal Products for Human Use of European Medicines Agency (EMA) issued recommendations for compassionate use for remdesivir as the most promising treatment for COVID-19. The EMA explicitly states that the compassionate use is not part of the clinical trial in its usual meanings.IFLA (International Federation of Library Associations and Institutions) also wrote an open letter to WIPO urging WIPO to use all available flexible intellectual property mechanisms to maximize worldwide access to information (research data) on COVID-19 treatment.Thus, the legal regime of «Solidarity clinical trials and the WHO and EMA declarations lead us to conclude that all data obtained in the Solidarity clinical trials should not be monopolized by intellectual property, either as objects of patenting for a new scope / new purpose of treatment, or like an object of data exclusivity protection.

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Analysis of costs and strategies for using academic research in a private dental college to develop commercially viable products

10.1101/2020.06.02.129338 ◽

2020 ◽

Author(s):

Rampalli Viswa Chandra ◽

Devaraju Rama Raju

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Product Development ◽

Negative Impact ◽

Academic Research ◽

Research Projects ◽

Trial Duration ◽

Cycle Times ◽

Surgical Devices

ABSTRACTBackground & objectivesThe study had two aims. 1) Analysis of research projects done in our institution from 2014-2019 to identify products with a potential for commercialization and 2) To understand the effect of product-development variables on research projects to improve the quality of future commercialization-oriented trials.Methods338 clinical trials were grouped into 188 projects under the headings irrigants, diagnostic devices, surgical devices, biomaterials and gels. Trials per project, capital, material costs, labour and the cycle times per trial were calculated. To understand the effect these variables, five hypotheses were generated to test whether greater number of trials, successes, higher capital, more investigators per trial and a longer trial duration will result in a product worthy of commercialization.Results22 projects had products with a potential for commercialization. Except labour and cycle time (p>0.05), all variables showed significant differences across all projects. Three products were identified as having potential for actual commercialization. It was observed that greater number of trials (χ2=4.6793; p=0.030528) and successes (χ2=20.8134; p<0.00001) in a project along with a higher capital (χ2=12.2662; p=0.000461) will generate a product worthy of commercialization.Interpretation & conclusionsThe results seem to suggest that in trials for commercialization, emphasis must be placed on implementing multiple, well-designed clinical trials on a device or product to successfully identify whether it is commercialization-worthy or not. Due attention must be given to the financial aspects of the projects as deficiencies may result in negative impact on the flow and outcomes of a clinical trial.

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Motivation for and Barriers to Participation in Clinical Trials From the Perspective of Patients With Rheumatic Diseases and Chronic Musculoskeletal Pain

The Open Rheumatology Journal ◽

10.2174/1874312901812010332 ◽

2018 ◽

Vol 12 (1) ◽

pp. 332-345

Author(s):

Susann Vogt ◽

Ingo H. Tarner ◽

Ulf Müller-Ladner ◽

Ramona König

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Rheumatic Diseases ◽

Clinical Studies ◽

Family Doctor ◽

New Drugs ◽

Patient Recruitment ◽

Special Role ◽

Willingness To Participate ◽

Specialist Care

Background: Clinical studies are indispensable for the development and clinical introduction of new therapies. Particularly in the field of rheumatology, there is a high need for the development of new drugs because for most rheumatic diseases a curative treatment is not yet available. Furthermore, a large percentage of patients are not even treated adequately with approved treatment options. Treatment is particularly challenging for those entities that belong to the so-called orphan diseases because effective drugs have yet to be developed and approval of new drugs is difficult due to the fact that only small numbers of affected patients can be recruited for clinical trials. Despite the need for new developments and thus clinical studies, patient recruitment for clinical trials in Germany is generally difficult. Therefore, sponsors frequently use non-European study centers to enroll the necessary numbers of patients as inadequate patient recruitment leads to increased costs and delayed implementation of new medical knowledge. Objective: Given the overall limited recruitment rates for clinical studies in Germany, it was the aim of this work to gain insights into motivations for and barriers to participating in clinical trials in Germany from the patients’ point of view. Methods: Data was collected using a structured questionnaire in three groups of patients who are suffering from a rheumatic disease and are receiving specialist care. The completely anonymous questionnaire included a total of 32 questions, divided into four main topics. All questions could only be answered by yes or no or by selecting or not selecting a choice of the answer provided. Per question, proportions of patients selecting yes or no or any of the choices were compared between groups and between males and females. Results: It was found that there is a lack of education and knowledge about the nature and offer of clinical trials among patients with rheumatic diseases. This issue represents one of the main barriers to patient recruitment for clinical trials. In addition, a large proportion of patients are concerned about the possible adverse effects of study drugs and about being used as “guinea pigs”. While the internet and daily newspapers are rarely used for education regarding study participation, it became clear that the family doctor as a trusted person and possible network partner has a special role in improving patient willingness to participate in trials. Furthermore, interviewees hope for shorter waiting times at the doctor's office and a better, regular, more intensive medical care when participating in a clinical trial. Conclusion: Better and broader information of patients can be regarded as a key to better recruitment for clinical trials since many patients, on the one hand, have certain concerns about clinical trials but at the same time do see the potential for personal advantages when participating in a trial. Information events by patient organizations and specialist centers could be a way to reach out to patients and to break down barriers with regard to participation in clinical trials. Presentations by sponsors and established clinical trial centers and intensified networking with general practitioners and specialists could probably also enhance patient recruitment.

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Regulators, Pivotal Clinical Trials, and Drug Regulation in the Age of COVID-19

International Journal of Health Services ◽

10.1177/0020731420979824 ◽

2020 ◽

Vol 51 (1) ◽

pp. 5-13

Author(s):

Joel Lexchin ◽

Janice Graham ◽

Matthew Herder ◽

Tom Jefferson ◽

Trudo Lemmens

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Drug Administration ◽

Food And Drug Administration ◽

Drug Regulation ◽

New Drugs ◽

European Medicines Agency ◽

Approval Process ◽

Health Canada ◽

Clinical Trial Information

Medicine regulators rely on pivotal clinical trials to make decisions about approving a new drug, but little is known about how they judge whether pivotal trials justify the approval of new drugs. We explore this issue by looking at the positions of 3 major regulators: the European Medicines Agency, Food and Drug Administration, and Health Canada. Here we report their views and the implications of those views for the approval process. On various points, the 3 regulators are ambiguous, consistent, and demonstrate flexibility. The range of views may well reflect different regulatory cultures. Although clinical trial information from pivotal trials is becoming more available, regulators are still reluctant to provide detailed information about how that information is interpreted. As medicines and vaccines come up for approval for treatment of COVID-19, transparency in how pivotal trials are interpreted will be critical in determining how these treatments should be used.

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