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.

China FDA mimics US clinical trial application process to accelerate drug approvals

China FDA CFDA clinical trial accelerate drug approvalsChina’s Food and Drug Administration (CFDA) set a goal to push drugs to clinics faster. How will they accomplish this goal? Recent policy proposals suggest CFDA are looking at the US Food and Drug Administration (FDA) for answers. Imitation is the greatest form of flattery, right?

The new CFDA policy proposals are twofold.  First, they suggest loosening restrictions on trial sites. By backing away from the current certification system, which requires any facility trying to conduct new clinical trials to go through a “laborious certification process,”1 CFDA should be able to foster new trial sites. Second, the agency is proposing a “no response means approval mechanism akin to the U.S. FDA’s trial approach [which would] cut the waiting time for researchers starting new studies.”1

CFDA’s proposed changes (Chinese) posted last week are very similar to the U.S. FDA’s Investigative New Drug (IND) process. The agencies current rules require a drug company to wait for CFDA’s official approval before proceeding with a clinical trial. Under the proposed rule, the agency would be allowed only 60 working days to reject or question an application before the application would automatically be considered a go. The 60-day deadline would still exceed U.S. FDA’s 30-day response window, but greatly reduce the 195-day average that CFDA currently maintains.1

It remains to be seen whether CFDA is capable of such a significant reduction of approval time. Still, reducing the red tape around trial sites and speeding up IND evaluations could do wonders for innovation within China’s life science sector. Demand for trial sites has “been scarce for years…the number of clinical trial sites has been a bottleneck in China for both innovative and generic drugs.”1 These policy proposals coupled with CFDA’s plans to admit foreign clinical trial data to support registration of biopharmaceuticals and medical devices could quickly transform the life science landscape in China.

Pearl IRB will continue to monitor the rules impacting clinical trials and human subject research abroad and domestically. If you need strategic study design support or have are seeking approval for your next study, contact our experts at Pearl IRB.



New FDA draft guidance points to problems with multiple endpoints in clinical trials

FDA clinical trials draft guidanceThe US FDA released draft guidance this week on the “problems posed by multiple endpoints in the analysis and interpretation of study results and how these problems can be managed in drug and biologic clinical trials,” Zachary Brennan of RAPS reports. The FDA justifies the guidance due to the greater likelihood of making false conclusions about the effects of a given drug as the number of endpoints in a single clinical trial increases.

The FDA states that the guidance serves to “describe various strategies for grouping and ordering endpoints for analysis and applying some well-organized statistical methods for managing multiplicity within a study in order to control the chance of making erroneous conclusions about a drug’s effects.” (FDA Draft Guidance). Efficacy endpoints measure a drug’s effects. They may include assessments of clinical events (e.g. mortality, pulmonary exacerbation), patient symptoms (e.g. pain, depression), measures of function (e.g. ability to walk or exercise), or surrogates of these events or symptoms. The draft guidance lists the three families for classifying endpoints within a clinical trial: primary, secondary, and exploratory. To demonstrate the study objective of effectiveness, a statistical analysis must be performed to rule out chance as the explanation for a trial’s results. The guidance goes on to discuss the test of hypothesis and several other statistical methods used within clinical research to test against the probability of chance.

The FDA’s explanation of various statistical models and their usage cases dominates the rest of the draft guidance. However, this in-depth analysis drives home the message of this guidance. The FDA states that “the chance of making a false positive conclusion, concluding that a drug has a beneficial effect when it does not, is of primary concern” (FDA Draft Guidance). Our team of experts at Pearl IRB strive to stay up to date with FDA’s guidance to ensure that our clients remain informed about the necessary regulations. This allows clinical trials to run smoothly as our clients march towards product commercialization. If you have a study that needs reviewed or are in the beginning phases of research for a new treatment, please contact us today.

FDA finalizes Guidance for Electronic Informed Consent

food and drug administration united statesDecember 2016 – The U.S. Food and Drug Administration (FDA) finalized its guidance intended for institutional review boards (IRBs), investigators, and sponsors engaged in (or responsible for) oversight of human subject research under the Department of Health and Human Services (HHS) and/or FDA regulations. The guidance, created in conjunction with the HSS and Office for Research Protections (OHRP), provides recommendations on the use of electronic systems and processes that may employ multiple electronic media to obtain informed consent.

Human drug and biological products, medical devices, and combinations thereof are included in the guidance. The information presented to a subject, processes used to obtain informed consent, and documentation of the electronic informed consent (eIC) must abide by the regulations set forth in the guidance. The FDA operationally defines eIC as “the use of electronic systems and processes that may employ multiple electronic media, including text, graphics, audio, video, podcasts, passive and interactive Web sites, biological recognition devices, and card readers, to convey information related to the study and obtain and document informed consent.” It is wise to define a detailed definition of eIC, for the term informed consent can mistakenly be understood as obtaining a handwritten signature on a written consent form. This represents only one piece of the consent process; it also includes providing the subject with adequate information to make a decision, ask questions, and ongoing communication throughout the study.

In addition to defining the full eIC process, the guidance provides answers to commonly asked questions concerning instituting an electronic informed consent process. For questions about the new guidance as it may relate to your current clinical research process, please contact us today to start a conversation.

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.

Getting the word out about clinical trials

Melissa Fassbender, of OutSourcing-Pharma, published an article about a SubjectWell survey on Clinical Trial Awareness and Attitudes. For those surveyed: 50% are not aware of clinical trials and 57% could not recall any advertising for clinical trials.

The lack of awareness suggests that pharma and even CRO’s need to get the word out to the public when rolling out clinical trials. Many people who have an interest in being part of advancing science are not aware of what studies exist. Have ideas on increasing the awareness of the importance of clinical trials and how to volunteer? Let us know. Pearl IRB can help with your clinical trial management with IRB reviews and more — contact us to partner on your next study.

Buch updates on FDA’s progress made for clinical trials

Barbara D. Buch, M.D., Chair of the 907 Steering committee and the Associate Director for Medicine in FDA’s Center for Biologics Evaluation and Research, recently posted on FDA Voice her reflections on a focused action plan to support inclusion of diverse populations in clinical trials. The plan focused on addressing quality, participation and transparency of data in clinical trials.

For improving quality of data collection, progress was reported in training and outreach of guidance on demographic data, modifications to clinical review templates for better inclusion of diverse populations, and more.

To meet the goal of increased participation, Dr. Buch shared that a workshop was held to discuss the importance of diversity in clinical trials, and she reported that clinical trial demographic information is now easily available online for consumers.

To improve transparency, FDA reported that a Language Access Plan Working Group was established for new communication strategies to reach those under-represented, and a pilot program was formed to make demographic information available for Biologics License Applications, and more.

Read Buch’s entire article here for more details on the progress made. Contact Pearl IRB for experienced assistance in your clinical research.

Join in Upcoming Life Sciences Lunch Series, February 16th with Diana Caldwell as panelist

The Indiana Health Industry Forum (IHIF) and Barnes & Thornburg present “Clinical Trials from a Study Site Perspective” featuring Pearl Pathways’ own President and CEO, Diana Caldwell as a panelist. This presentation and luncheon will be held on February 16th at the Barnes & Thornburg office at 11 S. Meridian Street in downtown Indianapolis, 11:30 – 1:00pm. Learn more and register today.

Wearable technology and clinical trials: beneficial or problematic?

Wearable technology has been taking over the consumer world for health and fitness, and speculation has grown around the topic of utilizing the devices in clinical trials. First Post Business addressed the idea, along with input from Michael Shanler, research director at Gartner. Shanler predicts many limitations may arise with the use of the technology, such as challenging infrastructure, security and privacy, and protocol development issues. Gartner expects that within the next two years, a maximum of 10% of clinical trials will attempt to utilize wearable technology; however there are many indirect determining factors for success. First Post states that not only will the life science companies need to ensure positive health outcomes, they must trust the technologies to accurately collect and measure data.

The use of wearables within the industry for research purposes is still in its early days, and the future will depend on any market shifts and continuous technological advances. Until then, more questions will arise and must be addressed about data, calibration, compliance and performance before these technologies are prevalent in the industry.

Click here to access the First Post article.