Rho site logo

Rho Knows Clinical Research Services

Cellular Therapy Studies: 7 Common Challenges

Posted by Brook White on Tue, May 15, 2018 @ 09:34 AM
Share:

Heather Kopetskie, Senior BiostatisticianHeather Kopetskie, MS, is a Senior Biostatistician at Rho. She has over 10 years of experience in statistical planning, analysis, and reporting for Phase 1, 2 and 3 clinical trials and observational studies. Her research experience includes over 8 years focusing on solid organ and cell transplantation through work on the Immune Tolerance Network (ITN)and Clinical Trials in Organ Transplantation (CTOT) project.  In addition, Heather serves as Rho’s biostatistics operational service leader, an internal expert sharing biostatistical industry trends, best practices, processes and training.

Kristen Much, Senior BiostatisticianKristen Mason, MS, is a Senior Biostatistician at Rho. She has over 4 years of experience providing statistical support for studies conducted under the Immune Tolerance Network (ITN) and Clinical Trials in Organ Transplantation (CTOT). She has a particular interest in data visualization, especially creating visualizations within SAS using the graph template language (GTL). 

Cellular therapy is a form of treatment where patients are injected with cellular material. cell therapyDifferent types of cells can be utilized such as stem cells (such as mesenchymal stem cells) and cells from the immune system (such as regulatory T cells (Tregs)) from either the patient or a donor. In many cases, these cells have been reprogrammed to carry out a new function that will aid in the treatment of a disease or condition. Cellular therapy has become increasingly-popular largely due to the fact that cells have the ability to carry out many complex functions that drugs cannot. When successful, cellular therapy can result in a more targeted and thus more effective treatment. More information on cellular therapy can be found here .

Rho is conducting several studies using cellular therapy to treat diseases such as systemic lupus erythematosus and pemphigus vulgaris and for various applications within organ transplantation.

Cellular therapy trials offer their own unique set of challenges. The following list presents some of these challenges encountered here at Rho.

  1. Cellular therapies require highly-specialized laboratories to manufacture the investigational product, especially if the cells are being manipulated. Centralized manufacturers are commonly utilized requiring logistical considerations if the trial has multiple study sites. These logistics may include proper packaging, temperature storage, shipping days, etc. which all must be considered when shipping the product.
  2. It is critical to plan for and establish clear communication between the manufacturing lab, the study site, and the study team when working under time constraints. One common consideration is to ensure extracted cells will not arrive at the manufacturer on a Saturday or Sunday when lab personnel may not be available to immediately process cells. 
  3. Protocols usually require a minimum number of cells be available for infusion into the subject. The protocol must detail what steps to take when not enough viable cellular product is produced. Some questions to consider include: 
    • Is it is possible to recollect cells for a second attempt? If so, does it work with the timing of the trial?
    • Are there leftover cells from the first attempt? 
  4. Potent drugs are sometimes paired with administration of the cellular product.  It is crucial to avoid administering these drugs unless a viable cellular product has been produced. Checks should be in place to ensure product is available before administering additional study drugs.
  5. Guidance exists limiting the amount of blood that can be collected over an 8-week period from a single subject. If the cellular product is manufactured from a blood donation, the amount of blood from any and all blood draws around the same time should be taken into consideration. If the blood donation occurs close to screening when blood is often drawn for various baseline labs pay close attention to the total amounts as exceeding the established limits can be easy. 
  6. The subject accrual for a study should be clearly outlined in the protocol. Is it X number of subjects that receive a minimum number of cells, X number of subjects that receive any cells, etc.
  7. Cellular product may not be administered until several months into the study. Subjects may be evaluated for eligibility several times while waiting for the infusion allowing multiple time points each subject may become ineligible. This along with the potential of insufficient cellular product can result in an unexpected length of time to administer cellular product to the target number of subjects. As such, this is an important factor when determining the duration and budget for a cellular therapy study. 
All in all, there are numerous opportunities for learning when using cellular therapies to treat disease. In many disease areas, this concept is still novel and study teams are facing new challenges with each study. Understanding these challenges early can help in the development of a robust protocol that addresses these same challenges before they ever become an issue.

“This drug might be harmful!  Why was it approved?”  What the news reports fail to tell us.

Posted by Brook White on Thu, Apr 19, 2018 @ 08:39 AM
Share:

Jack Modell, MD, Vice President and Senior Medical OfficerJack Modell, MD, Vice President and Senior Medical Officer is a board-certified psychiatrist with 35 years’ of experience in clinical research and patient care including 15 years’ experience in clinical drug development. He has led successful development programs and is a key opinion leader in the neurosciences, has served on numerous advisory boards, and is nationally known for leading the first successful development of preventative pharmacotherapy for the depressive episodes of seasonal affective disorder.

David Shoemaker, PhD, Senior Vice President, R&DDavid Shoemaker, PhD, Senior Vice President R&D, has extensive experience in the preparation and filing of all types of regulatory submissions including primary responsibility for four BLAs and three NDAs.  He has managed or contributed to more than two dozen NDAs, BLAs, and MAAs and has moderated dozens of regulatory authority meetings.  

Once again, we see news of an approved medication* being linked to bad outcomes, even deaths, and the news media implores us to ask:  

drugs and biologics in the news“How could this happen?”
“Why was this drug approved?”
“Why didn’t the pharmaceutical company know this or tell us about it?”
“What’s wrong with the FDA that they didn’t catch this?”
“Why would a drug be developed and approved if it weren’t completely safe?”

And on the surface, these questions might seem reasonable.  Nobody, including the drug companies and FDA, wants a drug on the market that is unsafe, or for that matter, wants any patient not to fare well on it.  And to be very clear at the outset, in pharmaceutical development, there is no room for carelessness, dishonesty, intentionally failing to study or report suspected safety signals, exaggerating drug benefits, or putting profits above patients – and while there have been some very disturbing examples of these happening, none of this should ever be tolerated.  But we do not believe that the majority of reported safety concerns with medications are caused by any intentional misconduct or by regulators failing to do their jobs, or that a fair and balanced portrayal of a product’s risk-benefit is likely to come from media reports or public opinion alone.

While we are not in a position to speculate or comment upon the product mentioned in this article specifically, in most cases we know of where the media have reported on bad outcomes for patients taking a particular medication, the reported situations, while often true, have rarely been shown to have been the actual result of taking the medication; rather, they occurred in association with taking the medication.  There is, of course, a huge difference between these two, with the latter telling us little or nothing about whether the medication itself had anything to do with the bad outcome.  Nonetheless, the news reports, which include catchy headlines that disparage the medication (and manufacturer), almost always occur years in advance of any conclusive data on whether the medication actually causes the alleged problems; and in many cases, the carefully controlled studies that are required to determine whether the observed problems have anything directly to do with the medication eventually show that the medication either does not cause the initially reported outcomes, or might do so only very rarely.  Yet the damage has been done by the initial headlines:  patients who are benefiting from the medication stop it and get into trouble because their underlying illness becomes less well controlled, and others are afraid to start it, thus denying themselves potentially helpful – and sometimes lifesaving – therapy.  And ironically, when the carefully controlled and adequately powered studies finally do show that the medication was not, after all, causing the bad outcomes, these findings, if reported at all, rarely make the headlines. 

Medications do, of course, have real risks, some serious, and some of which might take many years to become manifest.  But why take any risk?  Who wants to take a medication that could be potentially harmful?  If the pharmaceutical companies have safety as their first priority, why would they market something that they know carries risk or for which they have not yet fully assessed all possible risks?  There’s an interesting parallel here that comes to mind.  I recently airplane-1heard an airline industry representative say that the airlines’ first priority is passenger safety.  While the U.S. major airlines have had, for decades, a truly outstanding safety record, could safety really be their first priority?  If passenger safety were indeed more important than anything else, no plane would ever leave the gate; no passengers would ever board.  No boarding, no leaving, and no one could ever possibly get hurt.  And in this scenario, no one ever flies anywhere, either.  The airlines’ first priority has to be efficient transportation, though undoubtedly followed by safety as a very close second.  Similarly, the pharmaceutical industry cannot put guaranteed safety above all else, or no medications would ever be marketed.  No medications and no one could ever get hurt.  And in this scenario, no one ever gets treated for illnesses that, without medications, often harm or kill.  In short, where we want benefit, we must accept risks, including those that may be unforeseeable, and balance these against the potential benefits.

OK then:  so bad outcomes might happen anyway and are not necessarily caused by medication, worse outcomes can happen without the medications, and we must accept some risk.  But isn’t it negligent of a pharmaceutical company to market a medication before they actually know all the risks, including the serious ones that might only happen rarely?  Well, on average, a new medicine costs nearly three-billion dollars and takes well over a decade to develop, and it is tested on up to a few thousand subjects.  But if a serious adverse event did not occur in the 3000 subjects who participated in the clinical trials to develop the medicine, does this show us that the medicine is necessarily safe and unlikely to ever harm anybody?  Unfortunately, it does not.  As can be seen by the statistical rule of three**, this can only teach us that, with 95% confidence, the true rate of such an event is between zero and 1/1000.  And while it may be comforting that a serious event is highly unlikely to occur in more than 1/1000 people who take the medication, if the true rate of this event is, let’s say, even 1/2000, there is still greater than a 90% chance that a serious adverse event will occur in at least one person among the first 5000 patients who take the medication!  Such is the nature of very low frequency events over thousands of possible ways for them to become manifest.

So why not study the new medication in 10,000 subjects before approval, so that we can more effectively rule out the chances of even rarer serious events?  There is the issue of cost, yes; but more importantly, we would now be extending the time to approval for a new medicine by several additional years, during which time far more people are likely to suffer by not having a new and needed treatment than might ever be prevented from harm by detecting a few more very rare events.  There is a good argument to be made that hurting more people by delaying the availability of a generally safe medication to treat an unmet medical need in an effort to try to ensure what might not even be possible – that all potential safety risks are known before marketing – is actually the more negligent course of action.  It is partly on this basis that the FDA has mechanisms in place (among them, breakthrough therapy, accelerated approval, and priority review) to speed the availability of medications that treat serious diseases, especially when the medications are the first available treatment or if the medication has advantages over existing treatments.  When these designations allow for a medication to be marketed with a smaller number of subjects or clinical endpoints than would be required for medications receiving standard regulatory review, it is possible that some of these medications might have more unknown risks than had they been studied in thousands of patients.  In the end, however, whatever the risks – both known and unknown – if we as a society cannot accept them, then we need to stop the development and prescribing of medicines altogether.  

*Neither of the authors nor Rho was involved in the development of the referenced product.  This post is not a comment on this particular product or the referenced report, but rather a response to much of the media coverage of marketed drugs and biologics more broadly.

**In statistical analysis, the rule of three states that if a certain event did not occur in a sample with n subjects, the interval from 0 to 3/n is a 95% confidence interval for the rate of occurrences in the population.  https://en.wikipedia.org/wiki/Rule_of_three_(statistics)  

The probability that no event with this frequency will occur in 5000 people is (1 - .005)5000, or about 0.082.

Free Webinar: Expedited Development and Approval Programs

505(b)(2) vs ANDA: How Complex Drugs Fit In

Posted by Brook White on Tue, Feb 20, 2018 @ 08:42 AM
Share:

Choosing the Appropriate New Drug Application and Corresponding Abbreviated Development Pathway

Samantha Hoopes, PhD, RAC Integrated Product Development AssociateSamantha Hoopes, PhD, RAC is an Integrated Product Development Associate at Rho involved in clinical operations management and regulatory submissions.  Samantha has over 10 years of scientific writing and editing experience and has served as lead author on clinical and regulatory documents for product development programs for a variety of therapeutic areas.

Sheila Bello-Irizarry, PhD, RAC, Research ScientistSheila Bello-Irizarry, PhD, RAC, Research Scientist, is actively involved in protocol development, orphan-drug designation applications, and regulatory submissions including INDs and NDAs/BLAs. Her therapeutic area experience includes infectious diseases, immunology, vaccines, lung biology, musculoskeletal, and antibody-mediated therapy.  She contributed to developing vaccine candidates against malaria and MRSA infections and to the understanding of inflammatory processes during lung fungal infections.

regulatory pathways--ANDA and 505(b)(2)With the confirmation of a new Food and Drug Administration (FDA) Commissioner, Scott Gottlieb, M.D., in 2017, we have seen some changes in the regulatory environment with a new Drug Competition Action Plan and FDA draft guidances focused on introducing more competition into the drug market with the goal of increasing access to drugs that consumers need.  These guidance documents are meant to provide information on abbreviated approval pathways and provide clarity on the regulatory pathway for complex generic drugs in order to speed approval allowing for more competition in the market place, which may impact pricing.  

While it is important to understand how to navigate the complex generic drug approval pathway, it is first necessary to determine whether your drug product should be submitted as an abbreviated new drug application (ANDA) for approval as a generic or if it requires submission of a 505(b)(2) new drug application.  This particular issue is addressed in a new draft guidance, published 13 October 2017, “Determining Whether to Submit an ANDA or a 505(b)(2) Application.”  The draft guidance defines an ANDA as an application for a duplicate (same with respect to their active ingredient[s], dosage form, route of administration, strength, previously approved conditions of use, and labeling [with certain exceptions]) of a previously approved drug product that relies on FDA’s findings that the previously approved drug product, the reference listed drug, is safe and effective.  An ANDA may not be submitted if studies are necessary to establish the safety and effectiveness of the proposed product.  A 505(b)(2) application contains full reports of safety and effectiveness, but one or more of the investigations relied upon by the applicant for approval were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted  [Guidance for Industry:  Applications Covered by Section 505(b)(2)]. 

The draft guidance outlines regulatory considerations for ANDA and 505(b)(2) applications as described below.  FDA will generally refuse to file a 505(b)(2) application for a drug that is a duplicate of a listed drug and eligible for approval via an ANDA.  An applicant may submit a suitability petition (21 CFR 314.93) to the FDA requesting permission to submit an ANDA, known as a petitioned ANDA, for a generic drug product that differs from the RLD in its dosage form, route of administration, strength or active ingredient (in a product with more than one active ingredient).  The FDA will not approve a suitability petition if determined that safety and effectiveness of the proposed changes from the reference listed drug cannot be adequately evaluated without data from investigations that exceed what may be required for an ANDA or the petition is for a drug product for which a pharmaceutical equivalent has been approved in an NDA.  The FDA will not accept an ANDA for filing for a product that differs from the reference listed drug until the suitability petition has been approved.

In some circumstances, an applicant may seek approval for multiple drug products containing the same active ingredient(s), known as bundling, when some of the products would qualify for approval under the 505(b)(2) pathway and some of the product would qualify for approval under the ANDA pathway.  The FDA allows the applicant to submit one 505(b)(2) application for all such multiple drug products that are permitted to be bundled.  An example referenced in the draft guidance where bundling into one 505(b)(2) submission would be allowed includes an applicant seeking approval of multiple strengths of a product where only some of which are listed in the Orange Book, as reference listed drugs. 

formal meetings with FDASeveral draft guidance documents have recently focused on complex generic drug products.  A draft guidance titled “Formal Meetings Between FDA and ANDA Applicants of Complex Products Under GDUFA” was issued in October 2017 to provide ANDA applicants information on preparing and submitting meeting requests and meeting materials for complex generic drug products.  Complex products are defined as 1)  complex active ingredients, complex formulations, complex routes of delivery, complex dosage forms, 2)  complex drug-device combination products, or 3) other products where complexity or uncertainty concerning the approval pathway or possible alternative approach would benefit from early scientific engagement.  The guidance describes 3 types of meetings for complex products that may be submitted as an ANDA:  product development meetings, pre-submission meetings, and mid-review-cycle meetings. The draft guidance include details for how it is determined if meetings are granted and the review timeframe goals for FY2018 through FY2022.  

A draft guidance “ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin” also issued in October 2017, focuses on helping applicants determine if certain complex products, synthetic peptides, that refer to a previously approved peptide drug product of recombinant deoxyribonucleic acid (rDNA) origin should be submitted as an ANDA.  In the past, analytical methods have not been capable of adequately characterizing peptide products for submission in an ANDA; however with advances in scientific technology, FDA now considers it possible to demonstrate that the active ingredient in a proposed generic synthetic peptide is the same as the active ingredient in the reference listed drug of rDNA origin.  While this guidance pertains to some specific synthetic peptides, Dr. Gottlieb addressed (FDA Voice, 02 October 2017) this general issue stating that “a further barrier to generic competition for certain complex drug products is the lack of established methods for showing the sameness of the active ingredient of a proposed generic drug to a brand-name drug for certain complex drugs” and “over the next year, FDA’s generic drug regulatory science program will work to identify gaps in the science and develop more tools, methods, and efficient alternatives to clinical endpoint testing, where feasible.”  These efforts are meant to encourage and facilitate complex generic drug development.  Additional guidance documents will continue to be released regarding specific types of complex drug products.

Additionally, a draft guidance released on 03 January 2018 “Good ANDA Submission Practices,”addresses common, recurring deficiencies seen in ANDAs that may lead to delay in approval.  Common deficiencies include not correctly addressing patent and exclusivity information for the RLD, not providing adequate and properly prepared clinical summary data tables for bioequivalence studies, and not submitting draft container and carton labels with an accurate representation of the formatting that will be used for the final printed labels.  In a statement from Dr. Gottlieb, “it currently takes on average about 4 cycles for an ANDA to reach approval – not necessarily because the product will not meet our standards, but sometimes because the application is missing the information necessary to demonstrate that it does” (Press Release 03 January 2017).  This guidance as well as a new manual of policies and procedures (MAPP:  Good Abbreviated New Drug Application Assessment Procedures) aim to help reduce the number of review cycles ANDAs undergo prior to approval.  

These recently released draft guidance documents provide clarity on abbreviated approval pathways and highlight priorities of the FDA to increase competition in the marketplace with a focus on speeding generic approvals, including complex generic drug products.  

Webinar: Worried About Your Next FDA Meeting?

The Future, Today: Artificial Intelligence Applications for Clinical Research

Posted by Brook White on Tue, Feb 13, 2018 @ 08:37 AM
Share:

Petra LeBeau, ScD, Senior Biostatistician and Lead of the Bioinformatics Analytics TeamPetra LeBeau, ScD, is a Senior Biostatistician and Lead of the Bioinformatics Analytics Team at Rho. She has over 13 years of experience in providing statistical support for clinical trials and observational studies, from study design to reporting. Her experience includes 3+ years of working with genomic data sets (e.g. transcriptome and metagenome). Her current interest is in machine learning using clinical trial and high-dimensional data.

Agustin Calatroni, MS, is a Principal Statistical Scientist at Rho. His academic background includes a master’s degree in economics from the Univesité Paris 1 Panthéon-Sorbonne and a master’s degree in statistics from North Carolina State University. In the last 5 years, he has participated in a number of competitions to develop prediction models. He is particularly interested in the use of stacking models to combine several machine learning techniques into one predictive model in order to decrease the variance (bagging), bias (boosting) and improve the predictive accuracy.

Derek Lawrence, Senior Clinical Data ManagerDerek Lawrence, Senior Clinical Data Manager, has 9 years of data management and analysis experience in the health care / pharmaceutical industry. Derek serves as Rho’s Operational Service Leader in Clinical Data Management, an internal expert responsible for disseminating the application of new technology, best practices, and processes.

artificial intelligence in clinical researchArtificial Intelligence (AI) may seem like rocket science, but most people use it every day without realizing it. Ride-sharing apps, airplane ticket purchasing aggregators, ATM machines, recommendations for your next eBook or superstore purchase, or the photo library within your smartphone—all these common apps use machine learning algorithms to improve the user experience.

Machine learning (ML) algorithms make predictions and, in turn, learn from their own predictions resulting in improved performance over time. ML has slowly been making its way into health research and the healthcare system due in part to an exponential growth in data stemming from new developments in technology like genomics. Rho supports many studies with large datasets including the microbiome, proteome, metabolome, and the transcriptome. The rapid growth of health-related data will continue along with the development of new methodologies like systems biology (i.e. the computational and mathematical modeling of interactions within biological systems) that leverage these data. machine learning in clinical researchML will continue to be a key enabler in these areas. The ever-increasing amounts of computational power, improvements in data storage devices, and falling computational costs have given clinical trial centers the opportunity to apply ML techniques to large and complex data which would not have been possible a decade ago. In general, ML is divided into two main types of techniques: (1) Supervised learning, in which a model is trained on known input and output data in order to predict future outputs, and (2) unsupervised learning, where instead of predicting outputs, the system tries to find naturally occurring patterns or groups within the data. In each type of ML, there a large number of existing algorithms. Example supervised learning algorithms include random forest, boosted trees, neural networks, and deep neural networks just to name a few. Similarly, unsupervised learning has a plethora of algorithms.

Lately, it has become clear that in order to substantially increase the accuracy of a predictive model, we need to use an ensemble of models. The idea behind ensembles is that by combining a diverse set of models one is able to produce a stronger, higher performing model which in turn results in better predictions. By creating an ensemble of models, we maximize the accuracy, precision, and stability of our predictions. The power of the ensemble technique can be intuited with a real-world example: In the early 20th century, the famous English statistician Francis Galton (who created the statistical concept of correlation) attended a local fair. While there, he came across a contest that involved guessing the weight of an ox. He looked around and noticed a very diverse crowd; there were people like him who maybe had little knowledge about cattle, and there were farmers and butchers whose guesses would be considered that of an expert. In general, the diverse audience ended up giving a wide variety of responses. He wondered what would happen if he took the average of all these responses, expert, and non-expert alike. What he found was that the average of all the responses was much closer to the true weight of the ox than any individual guess alone. This phenomenon has been called the “wisdom of crowds.” Similarly, today’s best prediction models are often the result of an ensemble of various models which together provide a better overall prediction accuracy than any individual one would be capable of.

As data management is concerned, the current clinical research model is centered on electronic data capture systems (EDC), in which a database is constructed that comprises the vast majority of the data for a particular study or trial. Getting all of the data into a single system involves a significant investment in the form of external data imports, redundant data entry, transcription from paper sources, transfers from electronic medical/health record systems (EMR/EHR), and the like. Additionally, the time and effort required to build, test, and validate complicated multivariate edit checks into the EDC system to help clean the data as they are entered is substantial and can only utilize data that currently exist in the EDC system itself. As data source variety increases, along with surges in data volume and data velocity, this model becomes less and less effective at identifying anomalous data.

At Rho, we are investing in talent and technology that in the near future will use ML ensemble models in the curation and maintenance of clinical databases. Our current efforts to develop tools to aggregate that data from a variety of sources will be a key enabler. Similar to the ways the banking industry uses ML to identify ‘normal’ and ‘abnormal’ spending patterns and make real-time decisions to allow or decline purchases, ML algorithms can identify univariate and multivariate clusters of anomalous data for manual review. These continually-learning algorithms will enable a focused review of potentially erroneous data without the development of the traditional EDC infrastructure, saving not only time performing data reviews but also identifying potential issues of which we would normally have been unaware.

Webinar: ePRO and Smart Devices

Challenges in Clinical Data Management: Findings from the Tufts CSDD Impact Report

Posted by Brook White on Fri, Feb 09, 2018 @ 12:24 PM
Share:

Derek Lawrence, Senior Clinical Data ManagerDerek Lawrence, Senior Clinical Data Manager, has 9 years of data management and analysis experience in the health care/pharmaceutical industry.  Derek serves as Rho's Operational Service Leader in Clinical Data Management, an internal expert responsible for disseminating the application of new technology, best practices, and processes.

The most recent Impact Report from the Tufts Center for the Study of Drug Development presented the results of a study including nearly 260 sponsor and CRO companies into clinical data management practices and experience. A high-level summary of the findings included longer data management cycle times than those observed 10 years ago, delays in building clinical databases, a reported average of six applications to support each clinical study, and a majority of companies reporting technical challenges as it pertained to loading data into their primary electronic data capture (EDC) system.

These findings represent the challenges those of us in clinical data management are struggling with given the current state of the clinical research industry and technological changes. EDC systems are still the primary method of data capture in clinical research with 100% of sponsors and CROs reporting at least some usage. These systems are experiencing difficulties in dealing with the increases in data source diversity. More and more clinical data are being captured by new and novel applications (ePRO, wearable devices, etc.) and there is an increased capacity to work with imaging, genomic, and biomarker data. The increases in data changing EDC paradigmvolume and data velocity have resulted in a disconnect with the EDC paradigm. Data are either too large or are ill-formatted for import into the majority of EDC systems common to the industry. In addition, there are significant pre-study planning and technical support demands when it comes to loading data into these systems. With 77% of sponsors and CROs reporting similar barriers to effective loading, cleaning, and use of external data, the issue is one with which nearly everyone in clinical research is confronted.

EDC integrationRelated to the issues regarding EDC integration are delays in database build. While nearly half of the build delays were attributed to protocol changes, just over 30% resulted from user acceptance testing (UAT) and database design functionality. Delays attributed to database design functionality were associated with a LPLV-to-lock cycle time that was 39% longer than the overall average. While the Tufts study did not address this directly, it would be no great stretch of the imagination to assume that the difficulties related to EDC system integration are a significant contributor to the reported database functionality issues. With there already being delays associated with loading data, standard data cleaning activities that are built into the EDC system and need to be performed before database lock would most certainly be delayed as well.

Clinical data management is clearly experiencing pains adapting to a rapidly-shifting landscape in which a portion of our current practices no longer play together nicely with advances in data-mining.jpgtechnology and data source diversity. All of this begs the question “What can we do to change our processes in order to accommodate these advances?” At Rho, we are confronting these challenges with a variety of approaches, beginning with limiting the impulse to automatically import all data from external vendors into our EDC systems. Configuring and updating EDC systems requires no small amount of effort on the part of database builders, statistical programmers, and other functional areas. Potential negative impacts to existing clinical data are a possibility when these updates are made as part of a database migration. At the end of the day, importing data into an EDC system results in no automatic improvement to data quality and, in some cases, actually hinders our ability to rapidly and efficiently clean the data. In developing standard processes for transforming and cleaning data external to the EDC systems, we increase flexibility in adapting to shifts in incoming data structure or format and mitigate the risk of untoward impacts to the contents of the clinical database by decreasing the prevalence of system updates.

The primary motivation for loading data received from external vendors into the EDC system is to provide a standard method of performing data cleaning activities and cross-checks against the clinical data themselves. To support this, we are developing tools to aggregate that data from a variety of sources and assemble them for data cleaning purposes. Similar to the ways the banking industry uses machine learning to identify ‘normal’ and ‘abnormal’ spending patterns and make real-time decisions to allow or decline purchases, similar algorithms can identify univariate and multivariate clusters of anomalous data for manual review. These continually-learning algorithms will enable a focused review of potentially erroneous data without the development of the traditional EDC infrastructure. This will save time performing data reviews and also identify potential issues which we would normally miss had we relied on the existing EDC model. With the future state resulting in an ever-broadening landscape of data sources and formats, an approach rooted in system agnosticism and sound statistical methodology will ensure we are always able to provide high levels of data quality.

Revised Draft Guidance:  Formal Meetings with the FDA for Drug Products

Posted by Brook White on Wed, Jan 17, 2018 @ 10:52 AM
Share:

Samantha Hoopes, PhD, RAC, Integrated Product Development AssociateSamantha Hoopes, PhD, RAC is an Integrated Product Development Associate at Rho involved in clinical operations management and regulatory submissions.  Samantha has over 10 years of scientific writing and editing experience and has served as lead author on clinical and regulatory documents for product development programs for a variety of therapeutic areas.

David Shoemaker, PhD, Senior Vice President R&DDavid Shoemaker, PhD, Senior Vice President R&D, has extensive experience in the preparation and filing of all types of regulatory submissions including primary responsibility for four BLAs and three NDAs.  He has managed or contributed to more than two dozen NDAs, BLAs, and MAAs and has moderated dozens of regulatory authority meetings.  

On 29 December 2017, the FDA released a revised draft guidance “Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products.”  This draft guidance will replace the previous draft guidance posted in 2015 on this topic.  According to the draft guidance, from this point in time there will be 4 types of formal meetings with FDA staff:  

  • Type A
  • Type B
  • Type B (end of phase [EOP])
  • Type C

An overview of each type of meeting and the changes from the previous version of the draft guidance are highlighted below: 

A Type A meeting is necessary for a stalled product development program (at the behest of FDA) to proceed or to address an important safety issue.  Meetings of this type include dispute resolution meetings, meetings to discuss clinical holds, special protocol assessment resolution meetings, and post-action meetings requested within 3 months after an FDA regulatory action other than approval (i.e. complete response letter).  In the revised draft guidance, meetings requested within 30 days of FDA issuance of a refuse-to-file letter were also designated as Type A meetings.  For Type A meetings, FDA will aim to respond to a meeting request letter within 14 calendar days of receipt.  If a Type A meeting is granted, the meeting will be scheduled or a written responses only (WRO) communication will be sent within 30 calendar days from FDA receipt of the meeting request letter.  The requester must submit the Type A meeting package at the same time the meeting request letter is submitted and the FDA aims to provide preliminary responses no later than 2 calendar days prior to the scheduled meeting. 

Type B meetings include:  pre-investigational new drug application (pre-IND) meetings, pre-emergency use authorization meetings, pre-new drug application (pre-NDA)/pre-biologics license application (pre BLA) meetings, post-action meetings requested 3 or more months after an FDA regulatory action other than approval, meetings regarding risk evaluation and mitigation strategies of postmarketing requirements that occur outside the context of the review of a marketing application, and meetings held to discuss the overall development program for products granted breakthrough therapy designation status.  With the release of the revised draft guidance EOP1 and EOP2 (pre-phase 3) meetings no longer fall within this meeting category.  The FDA will aim to respond to requests for Type B meetings within 21 calendar days of receipt.  If the meeting is granted, the meeting will be scheduled or alternatively if the meeting is not granted WRO communication may be sent within 60 calendar days from FDA receipt of the meeting request.  The requester must submit the Type B meeting package no later than 30 days before the scheduled date of the meeting or WRO communication.  The FDA aims to provide preliminary responses no later than 2 calendar days prior to the scheduled meeting.

The revised draft guidance introduces a new category of meetings, Type B (EOP) meetings, which will include EOP1 meetings for certain products that will be considered for marketing approval under 21 CFR part 12, subpart E (Hearing Procedures), or 21 CFR part 314, subpart H (Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses; Guidance for Industry Expedited Programs for Serious Conditions – Drugs and Biologics), and EOP2 meetings.  The FDA will aim to respond to requests for Type B (EOP) meetings within 14 calendar days of receipt.  If granted, a meeting will be scheduled or WRO communication will be sent within 70 calendar days of FDA receipt of the request.  The requester must submit the Type B (EOP) meeting package no later than 50 days before the scheduled date of the meeting or WRO response time.  As compared with Type B meetings, the FDA will aim to respond quicker to a Type B (EOP) meeting request; however, there will be a longer timeframe for scheduling the meeting and meeting packages will need to be sent in sooner due to the time required for FDA to review the greater volume of information contained in these meeting packages.  The FDA aims to provide preliminary responses no later than 5 calendars prior to the meeting and the requester should respond to the FDA within 3 calendar days after receiving the preliminary responses stating whether the meeting is still needed and providing an updated agenda including any questions that still require discussion.

A Type C meeting is any meeting other than a Type A, Type B, or Type B (EOP) meeting regarding the development and review of a product.  The revised draft guidance expanded this definition to specifically include meetings to facilitate early consultations on the use of a biomarker as a new surrogate endpoint that has never been previously used as the primary basis for product approval in the proposed context of use.  The FDA will aim to respond to meeting request letters for a Type C meeting within 21 calendar days of receipt.  If granted, a meeting will be scheduled or WRO communication will be sent within 75 calendar days of FDA receipt of the meeting request letter.  The revised draft guidance also specifies that meeting packages for Type C meetings that are requested as early consultations on the use of a new surrogate endpoint must be submitted at the time the meeting request is submitted while all other Type C meeting packages must now be submitted no later than 47 days before the scheduled date of the meeting or WRO response time.  According to the revised draft guidance, the FDA now aims to provide preliminary responses 5 calendar days prior to a scheduled Type C meeting and requires the requester to respond within 3 calendar days after receipt of FDA’s preliminary responses.

A summary of this information is provided in the table below (Appendix   Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products).

Meeting Type FDA Response to Request FDA Reciept of Meeting Package FDA Preliminary Responses to Requester (if applicable) Requester Response to FDA Preliminary Response (if applicable) FDA Scheduled Meeting Date (days from receipt of request) FDA Meeting Minutes to Requester (if applicable)
A 14 days With meeting request No later than 2 days before meeting -- Within 30 days 30 days after meeting
B 21 days No later than 30 days before meeting No later than 2 days before meeting -- Within 60 days 30 days after meeting
B (EOP)* 14 days No later than 50 days before meeting** No later than 5 days before meeting No later than 3 days after receipt of preliminary responses Within 70 days 30 days after meeting
C 21 days No later than 47 days before meeting*** No later than 5 days before meeting No later than 3 days after receipt of preliminary responses Within 75 days 30 days after meeting

Not applicable to written response only.
* EOP = end of phase
** If the scheduled date of a Type B (EOP) meeting is earlier than 70 days from FDA receipt of the meeting request, the requester’s meeting package will be due no sooner than 6 calendar days after FDA response time for issuing the letter granting the meeting (see Table 1 in section VI.B., Meeting Granted).
*** If the scheduled date of a Type C meeting is earlier than 75 days from FDA receipt of the meeting request, the meeting package will be due no sooner than 7 calendar days after FDA response time for issuing the letter granting the meeting (see Table 1 in section VI.B., Meeting Granted). Note that for Type C meetings that are requested as early consultations on the use of a new surrogate endpoint to be used as the primary basis for product approval in a proposed context of use, the meeting package is due at the time of the meeting request.

Consistent with the draft guidance from 2015, each meeting type consists of 3 different formats:  face-to-face, teleconference/videoconference, and written response only (WRO) and the FDA will issue finalized meeting minutes within 30 calendar days after any type of meeting.  The revised guidance still notes that requesters should attempt to combine product development issues into the fewest possible meetings.  Information pertaining to the content of a meeting request letter and meeting package is also outlined in the revised draft guidance.  According to the Federal Register, comments should be submitted on this revised draft guidance by 29 March 2018.   

An additional related resource includes the recently finalized guidance outlining the“Best Practices for Communication Between IND Sponsors and FDA During Drug Development.” 

Webinar: Worried About Your Next FDA Meeting?

What Makes a SuperheRho: More Than a Coworker in a Cape

Posted by Karley St. Pierre on Tue, Nov 14, 2017 @ 09:33 AM
Share:

“Who’s your favorite superhero?” No matter your age or gender, this question is commonly asked. It’s an ice-breaker of sorts—a response can tell a lot about someone’s personality and values. There are the typical, almost obvious answers—Batman, Superman, etc. Maybe you’d have a Marvel enthusiast throw in Iron Man for good measure. Or you could have someone aptly choose Wonder Woman as their favorite, what with this year’s blockbuster film making great strides in its genre. Regardless of who you choose the idea behind it is the same: who is someone you look up to, someone who can do anything incredibly. Superheroes are often thought of as being larger-than-life, having these unbelievable powers and instincts. They make great characters because their attributes are so incredible and uncommon. Yet, what we often forget is that we actually have superheroes around us every day, in real life—and at Rho. Between conducting clinical trials, giving keynote speeches at conferences, and participating in local philanthropy events, employees at Rho consistently go above and beyond. So, it comes as no surprise that we showcase our superhero staff when the time is right.

This past September, Rho celebrated being named to the Triangle Business Journal’s “Best Places to Work” list for 2017. The local publication holds nominations each year and honors the winners at a celebratory luncheon. Rho has been fortunate to receive this honor for 6 consecutive years, and each year Rho’s attendees choose their favorite hero-inspired shirt to wear. “When I was asked what character I wanted to be, at first I thought it was silly,” said Lane Bissett, a Business Development Associate with Rho. “Of course, I picked Wonder Woman like all the other ladies, but when I put on the shirt, it hit me.” Lane said that seeing herself alongside her Rho teammates, all wearing their chosen superhero tees, put an idea in her head. “We all are so different, but we all have these qualities that make us work great as a team. Representing Rho as this unified group of people felt really surreal.” Much like superhero squads in the movies, our team at Rho consists of many different personalities, strengths and talents. Whether it be a Clinical Research Associate or a Clinical Project Manager, every Rho employee has the opportunity to showcase their skill and knowledge while also learning from others. It’s a kind of collaboration that not only works but can be hard to find. 

21762788_1889648361053166_2032741538705477340_o.jpg

It’s this idea that makes Rho special—this unification of people and personalities towards one purpose and goal.  At Rho, that core purpose is to improve health, extend life, and enhance quality of life through corporate and research excellence. Each employee who represented Rho at the Triangle Business Journal Luncheon came from different sectors, holding different positions within the organization. “I was really proud when the announcers mentioned how Rho has won for the past 6 years,” said Joyce Lau, Research Associate. “It made us all feel kind of invincible,” she continued, “and it made me realize that there is a reason we can call ourselves superheroes here. We definitely had the most spirit, and it showed!” Throughout those 6 years, Rho has continued to see tremendous growth and opportunity, especially when it comes to adding more superheroes to the team. “When I came to Rho, the first thing I noticed was how great the people are,” Lane added. “Every day I feel lucky to work with the people I do, and it makes me excited to think of new hires joining and getting to see how amazing we are.” 

Shortly after Rho was honored at TBJ’s luncheon, we also celebrated our fiscal year end. At the celebration, employees were able to enjoy delicious food, interact with our CEOs and founders, and take home some pretty awesome Rho backpacks. “It felt like an early Christmas,”  said Joyce. “It just goes to show how much the people at Rho really care about you, really going above and beyond what you’d expect.” The year end celebration was a superhero convention it its own way—all our phenomenal heroes in one place.

FullSizeR.jpg

It’s not just the luncheons and gatherings that make us excited and proud to wear the title of “SuperheRho.” Just like the characters in comic books, every day brings a new challenge to face and every day we get to use our strengths to rise to the occasion. Recognition can be nice, but that’s not why superheroes do what they do. There’s an internal push for excellence and success, which Rho mirrors in our core values. So when we get asked who our favorite superhero is, chances are it’s someone here at Rho.

 

Highlights from TEDMED 2017

Posted by Brook White on Tue, Nov 07, 2017 @ 04:49 PM
Share:

TEDMED TheatreLast week I had the opportunity to attend TEDMED 2017 in Palm Springs and want to share some highlights of the experience.  This certainly isn’t a comprehensive summary, but rather highlights of some of the themes that were most interesting to me.  

Understanding the Brain

In order to make significant progress on mental illness and neurological disorders, we need a better understanding of how the brain works.  Several speakers shared progress and innovation in understanding the brain.  Geneticist Steven McCarroll discussed drop-seq, an innovative method for understanding which cell types have which molecules.  Using this technology, his team has been looking at what genetic variations in individuals with schizophrenia may tell us about the underlying biology of the disease.  Chee Yeun Chang and Yumanity Therapeutics are using yeast to better understand how improper protein folding relates to brain disease.  Dan Sobek of Kernel discussed how electrical stimulation may be used to “tune” the brain both as a method for addressing brain diseases as well as increasing performance in normal brains.  Guo-Li Ming talked about creating organoids which are essentially mini-organs created using stem cells.  These organoids have been used to look at neural development and the Zika virus.  Jill Goldstein discussed sex differences in brain development and how that relates to disparities in the prevalence of some mental illnesses between sexes.  Collectively, it is amazing to see some of the progress that is being made on some very difficult diseases.

Delivering Healthcare on the Frontlines

Some of the most touching stories came from those on the frontlines of healthcare.  Dr. Farida shared her stories as the only OB-GYN left in Aleppo and what it meant to put herself and her family in danger to ensure women still had access to care.  Camilla Ventura is a Brazilian ophthalmologist who first connected ocular damage to Zika infection.  Dr. Soka Moses shared stories from the Ebola outbreak in Liberia and the challenges of delivering care with severe shortages of equipment, staff, and supplies.  Agnes Binagwaho returned to her home country of Rwanda following the genocide and told her story of rebuilding her country’s healthcare infrastructure.  Each of these stories was inspiring and a testament to humanity at its best. 

The Opioid Crisis

There were a number of talks as well as a discussion group focused on various aspects of the opioid crisis.  Perspectives were shared from law enforcement personnel, those working on harm reduction programs such as supervised injection sites, and treatment programs for addiction.  One of the most moving talks was given by Chera Kowalsky.  Chera is a librarian in the Kensington area of Philadelphia, an area that has been hit hard by the opioid crisis.  They’ve instituted an innovative program where librarians have been trained to deliver naloxone, and she shared her personal story of using naloxone to help save the life of one of the library’s visitors.  Despite the challenges posed by the crisis, it was uplifting to see the range of solutions being proposed as well as the commitment of those working on them.

The Hive

One of the most interesting aspects of TEDMED was the Hive. Each year, a selection of entrepreneurs and start-ups come to TEDMED to share their innovations in healthcare and medicine. These companies were available throughout the conference to talk with attendees. There was also a special session on day 2 where each entrepreneur had two minutes to share their vision with the audience.

Finally, perhaps the most valuable part of the experience was all of the people I had a chance to meet, each of whom is playing a unique role in the future of healthcare.

50 Must Have Travel Tips from Experienced CRAs

Posted by Brook White on Wed, Oct 25, 2017 @ 09:57 AM
Share:

Recently, I sat down with Clinical Team Leads Caitlin Hirschman and Jamie Christensen who have a combined 25 years of monitoring experience to learn more about the travel tips they’ve acquired over the years.  Here’s what they had to share:

luggage and packing

General

1.  Expect the unexpected.  Things will go wrong, so you just have to be patient and stay calm when you are traveling.  Going in with the expectation that everything will go according to plan is a recipe for dissatisfaction.

2.  Get loyal with an airline and hotel chain so you can reap the benefits of their rewards systems (when it isn’t cost prohibitive).  You’ll appreciate the free upgrades and other goodies that you’ll collect over time. 

3.  Have cash. It comes in handy for tips and other small items.

4.  Invest in comfortable shoes.  Wear flats and bring sneakers.

Luggage & Packing

5.  Travel with a backpack and a carry-on.  Using a backpack rather than a purse or tote bag leaves your hands free which will make things much easier.  The backpack can also serve as the go to bag while you are on-site.

6. Invest in a good carry-on.  Consider one that is small enough to fit under the seat if you’ll be going on lots of overnight trips.  That way you won’t have to gate check your bag if they run out of room in the overhead compartments or if you are on a small regional flight that doesn’t accommodate roller boards.

7. Keep a ready-to-go toiletry kit that you don’t have to repack each time that contains carry-on size liquids.

8. Aveeno makes face wipes that work well as a non-liquid facial cleanser.

9. Pack light. A good rule is to pack two shirts for each pair of pants and re-wear the pants.
10. Pack clothes that don’t require ironing.

11. Bring some candy. It can make a good pick me up when you are feeling worn down.
12. Gum can come in handy too.

13. Don’t forget your chargers.

14. De-clutter your wallet so you are only carrying what you really need.

Air Travel

15. TSA pre-check is totally worth it. Not only does it provide the convenience of not needing to take off your shoes and take things out of your bags at airport security, but the shorter lines can save you a lot of time especially at larger airports. (Rho pays for TSA pre-check for frequent travelers).

16. Delta and Southwest are favorites for airlines. If you take Southwest, it’s worth it to pay for the early bird check-in so you get a better seat assignment. The cost will be offset by what you might have spent checking your bag.air travel

17. Consider joining an airline club. It can provide a really nice break during a long layover or if you get stuck because of a flight cancellation. (Rho pays for airline club membership for frequent travelers).

18. In general, aisle seats are preferred, but window seats may be better for a redeye.

19. Make sure to get a seat close to the front of the plane if you have a close connection, even if it means taking a middle seat. A middle seat is definitely preferable to a missed connection.

20. Don’t bring fish or beef jerky to eat on the plane. Your fellow passengers will appreciate it.

21. Avoid connecting flights through New York area airports. Atlanta is a good airport for transfers.

Ground Transportation & Parking

22. Consider using Uber to get from home to the airport depending on how long you will be gone and what time your flights are departing and arriving. It can be substantially cheaper than parking and you get dropped off close to the terminal at most airports.

23. If you do need to park, consider using an off-site parking service. You can earn points, they provide amenities like coffee and newspapers, and drop you off right by the terminal and your car. It can also feel safer than walking through a parking garage late at night.

24. Consider using Uber or other ride-sharing services in cities where parking can be a problem. This may also be a good plan if your visit is at an academic site. University parking is notoriously problematic.

25. If you have a good taxi driver, get their card so you can use them for the rest of the trip or future trips to the same city. It also allows you to call ahead for a ride.

Hotels

26. Download a noise machine app. It can help you sleep better in new places—particularly noisy ones.

27. Don’t sleep naked. You never know when there will be an unexpected hotel fire alarm.

28. When visiting a new site, ask them for hotel and restaurant recommendations.

29. Ask for a higher level hotel floor (never ground floor).

Health and Wellness

30. Bring an empty refillable water bottle and then fill it once you are on the other side of airport security. It’s easy to get dehydrated while you are traveling, and this is an easy, cheap, and environmentally-friendly solution.

31. Bring snacks. You never know when you are going to be stuck somewhere that it isn’t convenient to get food or where food options aren’t great. You can also choose healthier snack foods when you pack them yourself rather than purchasing them at the airport.

32. Make a plan to get in a workout wherever you go. It is easy to ignore your health when you are traveling frequently. Bring workout clothes and sneakers.eat healthy when you travvel

33. Check with your gym to find out if they have satellite locations in areas where you frequently travel.

34. Some hotels offer workout clothes and shoes that you can rent.

35. Keep your sneakers in your backpack, so you can take a walk and explore the city after work.

36. Keep hand sanitizer or baby wipes handy. Planes and airports are germy places.

37. Look under the mattress to check for bedbugs.

38. Beach Body Workouts is super cheap for a year membership. Just log onto the app and choose a workout like yoga or T25, which is a super quick great workout.

Safety

39. Make sure someone has your contact information and also knows your travel plans. Make sure to give the airline an emergency contact number. This is especially important for single folks who aren’t necessarily checking in with anyone regularly.

40. When the hotel asks you how many keys you want, always tell them two so that no one overhears that you are traveling alone.

41. Do a safety check of the hotel room before settling in. Check behind doors and in closets where someone could be hiding and make sure windows and sliding glass doors are locked.

42. If you are traveling to a new place, try to arrive when it is still light outside.

Food & Entertainment

43. Headphones for the plane are a must. You can use them to listen to music or movies, and to drown out the noise of the plane (or unruly passengers).

44. Before you leave on your next trip, download movies, books, or audiobooks to entertain yourself on the plane or when you have some free time back at your room.

45. Learn to enjoy travel by exploring each place you go. There are a number of “Best of” apps that tell you the best sandwich, beer, dessert, etc. in each state. It can be fun to see how many you can collect.

46. Some restaurant and hotel chains have happy hours which can save you some money if you are traveling on a per diem reimbursement plan. In some cases, hotel happy hours provide free food that make for a decent light dinner.

47. Bring a bathing suit. If you have free time you can get some exercise in the pool or some relaxation time beside it.

48. Go see landmarks in new cities you visit—the Seattle Space Needle, Millennium Park in Chicago, Duck Tours in Boston, Riverwalk in San Antonio.

49. Baseball games are a great way to take in some local flavor at a reasonable cost.

50. Check out some local restaurants.

What are your best travel tips?  Share in the comments below!

View All Job Openings

Breaking Bad (Meetings)

Posted by Brook White on Tue, Sep 19, 2017 @ 10:57 AM
Share:

Ryan2.jpgRyan Bailey, MA is a Senior Clinical Researcher at Rho.  He has over 10 years of experience conducting multicenter asthma research studies, including theInner City Asthma Consortium (ICAC) and the Community Healthcare for Asthma Management and Prevention of Symptoms (CHAMPS) project. 

In Hamlet, Shakespeare posed the most famous existential question in English theater -- “To be, or not to be?”

If the Bard were to write a play for the 21st century office, he might ask a different, but no less poignant, question – “To meet, or not to meet?”

Few topics seem to elicit more workplace dread than the meeting. We tend to view meetings as disruptions, time sinks, resource devourers, and productivity killers. When someone says they “spent all day in meetings,” we don’t assume they got a lot accomplished; we assume their day was a bust.

Given the angst that seems to accompany meetings, we’ve been trying to rethink how we approach them at Rho. To help, we’ve been drawing inspiration from Deep Work, by Dr. Cal Newport. The premise of Deep Work is that our technology-driven culture is inadvertently inhibiting our ability to do focused, cognitively-demanding, high-impact work. Instead, our work is increasingly defined by fragmentation, interruption, and distraction, as we let our inbox and meeting schedule dictate the work we do.

Dr. Newport’s work struck a chord with us. Yet, we cannot escape the fact that our work requires the type of synchronous collaboration and context-rich communication that only meetings can provide. Here again we have an existential question: If meetings are so fundamentally important to our work, why are they so painful and disruptive?
Our honest take: We’re bad at them and we overuse them.

Most of us stink at meetings. We stink because we’ve fallen into the trap of thinking that meetings are easy. We show up and talk about the same stuff every week for an hour. What’s hard about that? In reality, effective meetings require thoughtful planning and careful execution from leaders, as well as mindful preparation and active participation from attendees.boring_meeting.jpg

Calendar software has exacerbated our problem by making it too convenient to schedule meetings. Rather than stopping to think if a meeting is needed, or if our objectives could be accomplished in a more effective way, we schedule the meeting because it’s easy. The classic example of this is the status update meeting. If the whole point of your meeting is to go around the room and give status updates to your teammates – something that could be done via email or chat with far less disruption – you have created a zombie meeting, an undead horror sucking the productivity out of your colleagues!

Many of us also have the bad habit of scheduling meetings as a form of procrastination. Instead of trying to solve a problem now, we punt it to our next meeting. While there’s nothing wrong with deferring a difficult issue until you can discuss it as a team, swamping the agenda with our postponed to-do lists is certain to “zombify” a meeting. The especially painful result of this tactic is that instead of taking a few minutes to solve the problem on our own, we multiply the resource burden. A 15-minute task dragged into an 8-person meeting effectively becomes a 2-hour task.

So, what’s to be done to salvage meetings and make them productive and engaging? One approach that we advocate among both meeting leaders and attendees is to follow the FSB mantra to meetings: Fewer. Shorter. Better. Here’s some advice we recently provided to our employees about FSB meetings:

Fewer – The challenge here is to not merely cut meetings, but to cut intelligently.  

  • Leaders: Think critically before you schedule a meeting.  Do you really need it?  Can you accomplish your objectives in a better way? For recurring meetings, take a look a day ahead of time and decide if you can cancel it. 
  • Attendees: Think critically before you attend a meeting. Do you need to be there? Read the agenda. Do you know which topics pertain to you? What will you contribute or learn? If you are unsure, contact the meeting coordinator and ask.
One alternative to cancelling a meeting is to rethink your meeting format. Could updates be sent from email and the meeting cancelled outright? Would a brief stand-up meeting suffice instead of an hour-long time drain? What about a brief teleconference from your desk? wood-table-meeting.jpg


Shorter – Meetings are notorious for taking up as much time as you allot for them. When you have back-to-back meetings, this leads to meeting room overlap, frustration, and the domino effect of late-starting meetings. Instead, try the 25/50 rule: reduce 30-minute meetings to 25 minutes and hour-long sessions to 50 minutes. This provides buffer to conclude your meeting and head to your next engagement on time.

Better – The single most important factor for better meetings is being prepared. Not knowing why you are at a meeting, what will be discussed, and what you hope to accomplish is certain to create a poor meeting.

  • Leaders: Serve your attendees well by following the basics of good meetings: 
    • Have a goal
    • Think critically about who should attend
    • Provide context ahead of time
    • Stay on time and on task
    • Endeavor to engage everyone in the room

If you are struggling with these steps, try setting aside time to prepare for your meetings.  You may also find that you are leading too many meetings.  In which case, you should share the load (this is a great way to help train up more junior team members!)

  • Attendees: Don’t settle for bad meetings.  Speak up and provide helpful, candid, and constructive feedback.  But also, when you’re in a meeting, be a helpful attendee:
    • Request that items be added to the agenda ahead of time
    • Come prepared to address the sections of the agenda you’re responsible for
    • Avoid the temptation to commandeer or disrupt the meeting

Meetings don’t have to be a source of frustration or disruption.  To the contrary, meetings can be some of the most productive times of our day – where we solve problems, brainstorm, and find creative inspiration – provided we execute them properly.  

When is the last time you did a self-evaluation of your meetings?  If it’s been a while (or never), consider taking 15 minutes this week to think critically and creatively about your current meetings.  How can they be pared back, truncated, and refined to make them more effective and productive?  When done right, following the FSB mantra can do a lot to return some much-needed productive time to your schedule.

Watch: Meet Our Experts