Updated clinical trial common protocol templates aim to speed up research, align objectives & endpoints

common protocol templates clinical trial research stockThe NIH-FDA Joint Leadership Council and TransCelerate BioPharma released updated common protocol templates (CPT) last week to accelerate clinical development. An Outsourcing-Pharma.com article and interview with TransCelerate CEO, Dalvir Gill, details some of the key additions to the new templates and how they will help advance research.

First and foremost, both the FDA/NIH and TransCelerate BioPharma templates aim to increase efficiencies in clinical trial protocol development. The FDA/NIH template is intended for NIH-funded studies. Global, multi-center trials requirements are covered by the Transcelerate CPT. During the interview, Gill described the key principles needed in a Common Protocol Document. “Structure must be streamlined and consistent, it must enable common wording relevant for all phases, and… it must enable endpoints that map to objectives and support the use of [Clinical Data Interchange Standards Consortium] CDISC therapeutic area standards,” Gill explained. These requirements acted as the foundation on which Gill and his team built the new common protocol template.

Aligning objectives to endpoints

The CPT includes new elements that align objectives to endpoints. Most importantly, the newly established level 1 and 2 heading structure allows sites and regulator reviewers to easily find information. These structural changes appear in both the Transcelerate and NIH-FDA protocol templates. Additionally, “establishing common endpoints aligned to CDISC Therapeutic Area standards and common language when used consistently will speed the time to first draft and reduce human errors,” Gill stated.

The existence of a Common Protocol Template will ease protocol interpretation and review by sites, IRBs, and regulators. Protocols have increased in complexity as the number of new studies registered in Clinicaltrials.gov steadily increases year-by-year. Sponsors currently provide protocols in their own structure and sites spend more time deconstructing and interpreting protocols. That time could be spent more effectively, Gill lamented, which justified the need for a structural alignment between protocols. “[The] collaboration with NIH-FDA to align structures of CPT and their newly released protocol template will take harmonization and information sharing even further… a harmonized template will also enable review and even comparisons of studies by regulators.”

Next steps for the CPT initiative could include changes in automation, content reuse, and traceability. Gill hopes that these next steps could further reduce the time to study startup. Pearl IRB provides expedited and full board ICF/protocol reviews. Our efficient, experienced team delivers superior IRB services that effectively balance the needs of human subjects, sponsors, and institutions. Contact us today to discuss your clinical research needs.

21st Century Cures Act: potential impact on the clinical research landscape

clinical trialsThe historic 21st Century Cures Act, written into law last December, is a 362-page bill comprised of several initiatives impacting the life sciences industry. The allocation of $4.8 billion for the “Cancer Moonshot” portion of the bill won over most headlines during news cycles leading up to the bill’s signing, but several other sections will impact the clinical research ecosystem over the next several years. An article published in this month’s volume of the Journal of Clinical Research Best Practices outlines the major sections of the Cures Act that affect clinical trials.

The aforementioned Cancer Moonshot leads the bill, creating a $4.8B “NIH Innovation Account” that will allocate funds to the Precision Medicine Initiative, BRAIN Initiative, Cancer, and Adult Stem Cells research. Another $500M will be set aside for an “FDA Innovation Account.” The Eureka Prize Competition section allocates prize money for significant advancements in biomedical sciences and/or improving health outcomes in serious yet disproportionate research areas. Three sections address confidentiality of personal health information for study participants: Privacy Protection for Human Research Subjects, Protection of Identifiable and Sensitive Information, and Data Sharing.

To support emerging scientists, the NIH will develop and prioritize policies that promote opportunities for new researchers. The NIH also addresses Educational loan repayment addresses by increasing repayments from $35k to $50k in exchange for research work in the areas of basic science, AIDS, and emerging needs. This section also instructs the NIH to prioritize research conducted by professionals from disadvantaged backgrounds.

Reducing administrative burden for researchers also makes up a large section of the bill. Within two years, HHS is to “harmonize and eliminate duplicative Conflict of Interest reporting… [and] examine the varying minimum thresholds, consider allowing for just in time reporting, and consider redefining which investigators and sub-investigators need to report.” Several sections address the patient experience during clinical trial studies. The FDA will create guidance explaining the use and requirement of patient experience data such as data collected by non-clinicians (e.g. patients, family, etc.), the impact of disease and therapy on patient lives, and patient treatment preferences.

The bill would not be complete without detailing the penalties for violation of grants, contracts, and other agreements created under the 21st Century Cures Act. The bill outlines fines from $10k-$50k for each false statement or omission in addition to $10k-$15k fines per day for delays in the transfer of funds to HHS.

Do you need assistance with your NIH funded research? Please contact us at Pearl IRB.

China closes cancer research gap: U.S. shoots for the moon

cancer research moonshotAmerica prides itself as a leader in technological innovation and medical research. Home to some of the largest and well respected cancer centers in the world, the U.S. has stood as the epicenter for cancer research for several decades. If the U.S. wishes to retain its spot as the clear leader in the global fight against cancer, celebration will have to wait for another day as a new report by Elsevier shows that China is narrowing the lead and race in cancer research.

The number of cancer-focused papers that Chinese researchers publish each year has tripled in the past decade, pushing China’s global share of cancer research publications to 17%. FierceBiotech breaks down the report, citing that increased R&D spending and a “shift from socialist economic planning to a more market driven system over the past decade” have catalyzed the country’s dramatic climb. Complacency does not seem to have intruded upon America’s collective psyche as evidence by the Cancer Moonshot. The purpose of the moonshot, announced earlier this year by the White House, is to “win the war on cancer.”

The Moonshot represents a massive collaboration across several industries united under a single goal to subdue cancer by 2020. The success of this initiative remains unknown. However, the recent passing of the 21st Century Cures Act in the House and Senate indicate that Moonshot will have a chance to play out over the next four years

EMA finds development challenges for medicines targeting CNS disorders in new report

The European Medicines Agency (EMA) released a report on Tuesday that analyzed over 100 applications submitted for medicines in the fields of psychiatry or neurology between 1995 and 2014. In the report, EMA concludes that various challenges can arise in the development of medicines targeting central nervous system (CNS) disorders and stresses the importance of appropriate design of early-stage clinical trials for future development success.

Complexity of research for CNS medicines adds to the challenge of successful drug development; EMA cites a “higher rate of failure during the clinical development of these products compared to other fields of medicine” in their report. Of the 103 applications received by EMA’s Committee for Medical Products for Human Use (CHMP), 57 were neurology products and 46 were psychiatry, and 29 were rejected or withdrawn leaving 74 that received approval. Submitted drugs targeted schizophrenia, MDD, Alzheimer’s disease, epilepsy, and more.

EMA’s claim that appropriate design of early-stage clinical trials is not ungrounded in fact. The analysis explains that “over 50% of the applications that had major problems with the outcome confirmatory study (in terms of efficacy and/or safety) also had issues in the early clinical development.” The chart below visualizes the report’s findings and the differences in the types of issues raised for neurology medicines and psychiatry medicines.

EMA report chart


Appropriate design of early-stage clinical trials is vital for resulting in efficacious results, and Pearl IRB is here to help. Please contact us to set up a discussion with our team of experts to assist with your drug or device clinical trials.

Advice from the experts: How to set up a successful community-based clinical trials program

Clinical research, when done correctly, provides a plethora of benefits to the researchers involved in the process as well as patients enrolled in the trials. Setting up a successful clinical trial process was the topic of a recent breakout session led by Daniel R. Saltzstein, MD and Lawrence Karsh, MD at the 2016 Large Urology Group Practice Association (LUGPA) Annual Meeting.

The two experts, as reported by OncLive.com, detailed several reasons why physicians should participate in clinical research. First and foremost, clinical research can contribute to the “greater good” of society by providing front-line therapies to patients in need at no cost. Karsh went on to explain the professional benefits clinical research provides as well: an ancillary revenue stream, increased number of publications, and credibility among the medical community. Karsh, who currently manages 35 trials that are either enrolling participants or ongoing, admits that he “think[s] it’s a huge bonus to learn how to use therapies before they even enter the market because it gives you the edge against other practices, [but] be clear that this won’t be a windfall and you can even lose money if it is not managed properly.”

Community physicians can be better strategic partners for pharmaceutical companies because they are able to “review proposals and contracts faster, recruit patients more rapidly, and offer an overall lower trial cost and greater diversity of [treatment states in their] patient base,” Saltzstein advises. Saltzstein and Karsh go on to list the vital positions for a successful clinical research program:

  1. Principal investigators
  2. Sub-investigators
  3. Director of research
  4. Study coordinators
  5. Data entry professional
  6. Recruiter and data miner to identify patients

Physical space within the clinic should not be forgotten either. Karsh suggests that “choosing space within eyeshot of referring doctors” helps keep the research program top of mind. Another key factor not to dismiss is earning buy-ins from colleagues. A coherent, well defined benefit statement of the program’s impact on patients and the clinic should be communicated to each participant. A prosperous program cannot be built overnight, as Karsh concludes that it “takes time and experience to start a research program – you will definitely go through some struggles… but the more trials you do, and do well, your name gets out and companies will come to you.”

For help from our experts at Pearl IRB on establishing or fine-tuning your clinical research program, please contact us to begin a conversation.

FDA Issues Official Withdrawal of Proposed Rule Concerning Public Disclosure of Unapproved Gene Therapies

Two weeks ago, the US Food and Drug Administration (FDA) announced the withdrawal of a proposed rule from 2001. The rule would have required the public disclosure of summaries of safety and effectiveness data from pre-market clinical trials of gene therapies and transplanted non-human tissues to humans.

In its notice of withdrawal, the FDA announced “[we have] reconsidered our position on the issue and deemed our concerns from 2001 outdated. We will continue to assess whether rulemaking in this area is necessary, and if so, we will proceed with a new proposed rule.”

RAPS explains that “non-proprietary and non-trade secret information and data related to investigational new drug applications (INDs) for xenotransplantation and gene therapies would have been disclosed.” RAPS goes on to detail the categories of information that would have been disclosed under the rule:

  1. product and patient safety data and related information, including results from preclinical and clinical studies and tests that demonstrate the safety and/or feasibility of the proposed procedures
  2. the name and address of the sponsor
  3. the clinical indications to be studied
  4. the protocol for each planned study, including a scientific abstract and a nontechnical abstract, a statement of the objectives, purpose, and rationale of the study, the name and address of each investigator, the name and address of the official contacts of each local review body as appropriate (IRB, IBC) and dated copies of approval by each group, the criteria for patient selection and exclusion, an estimate of the number of patients to be studied, a description of the treatment that will be administered to patients, and the clinical procedures, laboratory tests, or other measures to be taken to monitor the safety and effects of the drug in human subjects and to minimize risk
  5. written informed consent forms
  6. identification of the biological product(s) and a general description of the method of production, including a description of product features that may affect patient safety
  7. IND safety reports
  8. information submitted to FDA in an annual report
  9. the regulatory status of the investigation, the date of such action and the reason for such action
  10. other relevant data and information that the director of the Center for Biologics Evaluation and Research determines as necessary for the appropriate consideration of the public health and scientific issues, including relevant ethical issues

The FDA closed their notice of withdrawal by stating “the withdrawal of these proposals identified in this document does not preclude the Agency from reinstituting rulemaking concerning the issues addressed in the proposals listed in the chard. Should we decide to undertake such rulemakings in the future, we will re-propose the actions and provide new opportunities for comment.” If your company needs help navigating the FDA’s ever-changing rules and the complex regulatory landscape, please contact us.

Recent analysis suggests that large molecule clinical trials taking longer and costing more

KMR Group recently concluded an analysis spanning ten years, from 2005 to 2015, that evaluated cycle time performance for more than 17,000 interventional trials. The analysis investigates clinical trial differences by molecule type and shows an increase in both length of time and cost in large molecule clinical trials.

Several factors were analyzed: outsourcing, disease complexity, study size, and subject type. KMR Group found that large molecule trials are regularly longer at a statistically significant level and this is true across trial phases. For example, Phase III oncology trials for small molecules were found to have a median duration of 4.5 years versus 6.1 years for large molecules. Study startup, enrollment, and data capture are contributing factors to the extended trial time according to the report.

Upon reflection of the analysis, Linda Martin, President and Founder of KMR Group, stressed the importance of operational efficiency to Outsourcing-pharma.com, stating that “there may be some outstanding new biologic therapies on the horizon, but for the companies developing these drugs, identifying areas for operational improvement has never been more critical.”

Need assistance with your biologic clinical research study? Contact us to explore how we can help with study design, medical writing, IRB reviews, and clinical operations staff

Pearl IRB’s co -chair, Dr. Gretchen Parker published in Cureus

Gretchen Parker, PhD, RAC, CIP, and Pearl IRB Co-Chair, has completed another article published by Cureus.  The title of the article is “A Framework for Navigating Institutional Review Board (IRB) Oversight in the Complicated Zone of Research”.  The article provides Parker’s unique perspective on IRB processes and review types, offers insight into the IRB decision-making process, and emphasizes the importance of engaging an IRB consultant early in the clinical study design process.

Pearl Pathways’ own Diana Caldwell moderator at upcoming ACRP Circle City Chapter Symposium

CircleCity_Blue (1)Reminder to register for the October 3rd ACRP Circle City Chapter 16th annual fall symposium at the Ritz Charles in Carmel, IN.  Pearl Pathways’ CEO and President Diana Caldwell will moderate a panel discussion of The Future of Research in Indiana.  There will be additional discussions on clinical research throughout the day and an excellent opportunity for networking with other research professionals.  For a look at the agenda and to register click here.  You can learn more about ACRP Circle City Chapter and the benefits of being an active member at this link.

ACRP Circle City Chapter Symposium on October 3

CircleCity_Blue (1)On Monday, October 3rd, the ACRP Circle City Chapter will be hosting their 16th Annual Excellence in Clinical Research Symposium at the Ritz Charles in Carmel, Indiana.  Save the date for this event which will be held from 7:30am to 5:00pm.  Registration and agenda will be available soon.  For more information about the event, click here and contact Circle City ACRP at this link.