Remarks as prepared for delivery

Thank you, Professor [Jennifer] Arlen, for that kind introduction and for everything you and your colleagues have accomplished at NYU

A Georgia real estate investor pleaded guilty today for his role in conspiracies to rig bids and commit mail fraud at public real estate foreclosure auctions in Fulton and DeKalb counties, Georgia

Remarks as prepared for delivery

Thank you, Buddy [Wilmer Parker], for that kind introduction

A Las Vegas man pleaded guilty today to conspiracy for his role in an investment fraud scheme that promoted fraudulent investment opportunities and caused more than $5 million in losses to investors

The Justice Department today announced that Morgan Stanley will pay a $2

A Las Vegas man was sentenced today to 60 months in prison for his role in an investment fraud scheme that promoted fraudulent investment opportunities and caused more than $5 million in losses to investors

ALEXANDRIA, Va

By Sheila Plant, PhD, MHS, RAC, Senior Director, Regulatory Strategy, CATO SMS Special Interest Guidances/Information Date Posted Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components; Draft Guidance for Industry: Draft Guidance for Industry – Draft Guidance 30 Jan 2020 Arthroscopy Pump Tubing Sets …

Continue reading »

By Sheila Plant, PhD, MHS, RAC, Senior Director, Regulatory Strategy, CATO SMS    Special Interest Guidances/Information Date Posted Policy for Diagnostics Testing in Laboratories Certified to Perform High Complexity Testing under CLIA prior to Emergency Use Authorization for Coronavirus Disease-2019 during the Public Health Emergency: Immediately in Effect Guidance for Clinical Laboratories and Food and …

Continue reading »

By Sheila Plant, PhD, MHS, RAC, Senior Director, Regulatory Strategy, CATO SMS FDA guidances from March 2020 as well as upcoming advisory committee meeting announcements are below.  We note that approximately one-third of FDA’s guidances this past month are related to COVID-19.    Special Interest Guidances/Information Date Posted Enforcement Policy for Gowns, Other Apparel, and …

Continue reading »

By Ashley Henderson, PhD, CATO SMS Scientist 1.0 INTRODUCTION The COVID‑19 pandemic has added an unprecedented set of challenges to the conduct of clinical trials including quarantines, travel limitations, site closures, and interruptions in the supply chain of investigational products. In acknowledgement of these challenges, the Food and Drug Administration (FDA) recognizes that protocol modifications …

Continue reading »

By Zachary Swan, PhD, RAC, Associate Director, Regulatory Affairs at CATO SMS    Special Interest Guidances/Information Date Posted Exemption and Exclusion from Certain Requirements of the Drug Supply Chain Security Act During the COVID-19 Public Health Emergency: Guidance for Industry – Final Guidance 30 April 2020 FDA Deems Certain Tobacco Products Subject to FDA Authority, …

Continue reading »

The ongoing COVID-19 pandemic has sickened over 3.25 million people and has killed 233,014 people, according to data from Johns Hopkins University.

Lupin Pharmaceuticals Inc. (LUPIN, 500257) on Monday announced positive top-line results from its pivotal Phase 3 clinical trial to assess the efficacy and safety of single-dose Solosec or secnidazole 2g oral granules in 147 female patients with trichomoniasis.

Sutro Biopharma Inc.'s (STRO) interim phase I updated clinical data for a dose-escalation study of antibody drug-conjugate STRO-002 in ovarian cancer has been encouraging.

Avadel Pharmaceuticals plc's (AVDL) pivotal phase III trial evaluating FT218 for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy has met its three co-primary efficacy endpoints at all three doses.

Though it issued an Emergency Use Authorization (EUA) for anti-malaria drugs to treat or prevent coronavirus (COVID-19), the U.S. Food and Drug Administration (FDA) reiterated its warning about the known side effects of hydroxychloroquine and chloroquine, including serious and potentially life-threatening heart rhythm problems.

Today's Daily Dose brings you news about FDA approval of Immunomedics' breast cancer drug; promising results from Kiniksa Pharma's prurigo nodularis trial; Mallinckrodt's regulatory catalyst; Myovant Sciences' phase III SPIRIT 2 study results and another disappointment in Parkinson's disease drug development space.

The U.S. Food and Drug Administration granted marketing authorization to Medtronic Inc.'s CARPEDIEM System, a new device for continuous dialysis therapy for use in pediatric patients with certain kidney conditions. The system is indicated to provide continuous hemodialysis or hemofiltration therapy to critically ill pediatric patients weighing between 2.5 and 10 kilograms.

Baltimore, Maryland-based Medifast, Inc. is recalling certain Optavia Oatmeal products citing undeclared milk, a known allergen, the U.S. Food and Drug Administration said in a statement. The recall involves around 24,923 boxes of OPTAVIA Essential Old Fashioned Maple & Brown Sugar Oatmeal. The product is packaged in yellow and white cardboard boxes with the brand name.

Organicell Regenerative Medicine Inc. (BPSR.OB) has received FDA clearance to initiate a phase I/II multi-center clinical trial of Organicell Flow in patients diagnosed with moderate to severe acute respiratory syndrome (SARS) due to COVID-19 infection.

Today's Daily Dose brings you news about Bristol-Myers' CheckMate -743 study results; Cyclacel Pharma's entry into COVID-19 drug bandwagon; Exelixis touching a new 52-week high and Novartis exploring anti-malaria drug for COVID-19.

Let's take a look at the biotech/pharma companies that are slated to report clinical trial results this quarter.

The Health Impact Project’s toolkit contains resources that help communities, agencies, and other organizations take action to improve public health. The toolkit offers a collection of health impact assessments, guides, and other research to support policymakers’ efforts to consider health when making decisions across sectors, such as housing, planning, and education.

The spread of COVID-19 is placing unprecedented strain on Philadelphia’s hospitals, public health systems, and residents. Although the full effects of the emergency have yet to be realized, newly released data from 2018 and 2019 provides insight on the state of public health in the city before the pandemic.

Probi's largest clinical trial ever, focused on probiotic immune health, has recently been completed.

At Engredea 2018 in March in Anaheim, CA, OmniActive will be highlighting the latest addition to its ginger ingredient range, Gingever 10% powder, expanding its application to tablets, capsules and beverages.

The Organic Trade Association and The Organic Center on Thursday applauded Senators Bob Casey (D-PA) and Susan Collins (R-ME) for introducing The Organic Agriculture Research Act of 2018.

ChromaDex Corp. announced NIAGEN® nicotinamide riboside prevented neurological damage and improved cognitive and physical function in a new mouse model of Alzheimer’s disease.

The Council for Responsible Nutrition announced the launch of a consumer education initiative designed to raise awareness of Selective Androgen Receptor Modulators, a dangerous class of ingredients.

Obese mice with unhealthy lifestyles gain significantly less weight and avoid type 2 diabetes when they receive bacteriophages from the faeces of a lean mouse, according to a new University of Copenhagen study.

A recent study conducted by researchers at Tufts University suggests that consuming 1.5 ounces of almonds per day, compared to no almond consumption, may help reduce CVD risk factors such as elevated LDL cholesterol levels, and as a result, reduce an individual's healthcare costs associated with treating such conditions.

Ministers address developments in the global economy and take action to safeguard the region’s growth.

Finance Ministers from APEC member economies issued a joint statement reflecting the outcomes of the APEC Finance Ministers’ Meeting in Santiago, Chile, chaired by Chile’s Minister of Finance Felipe Larrain.

President Sebastián Piñera, Chair of APEC Chile 2019, announced that APEC Leaders’ Week will not be held in Chile this year.

Media Registration is Open for the APEC Informal Senior Officials’ Meeting

Members of the Asia-Pacific Economic Cooperation (APEC) will continue to work together towards more inclusive and sustainable growth, pledged APEC Senior Officials at the concluding event for Chile’s host year of APEC.

Chinese Taipei has voluntarily contributed USD 550,000 in funding to support APEC initiatives that advance regional economic integration and inclusive sustainable growth across the Asia-Pacific.

Broaden opportunities for people and ensure more inclusive growth across the Asia-Pacific, urged the 2020 Chair of APEC Senior Officials, host of the Asia-Pacific Economic Cooperation in 2020.

Stronger cooperation is essential for APEC as economies address inequality, environmental health, and the digital economy – the region’s critical challenges – said the APEC Secretariat’s Executive Director Dr Rebecca Sta Maria.

Media registration is open for the First APEC Senior Officials’ Meeting (SOM1) and related meetings in Putrajaya, Malaysia from 3 February to 22 February 2020.

2020 APEC Science Prize Open for Nominations

The first Senior Officials Meeting for APEC Malaysia 2020 begins

“I would like to express our appreciation to APEC member economies that put their faith in Malaysia’s leadership and made it a point to participate.”

La Serena Roadmap for Women and Inclusive Growth to bolster progress

Malaysia, the host of APEC 2020, has announced the postponement of the upcoming Second Senior Officials’ Meeting, the 2020 APEC Tourism Ministerial Meeting, and the 2020 APEC Ministers Responsible of Trade Meeting, which were scheduled for April this year.

From : Communities>>Regulatory Open Forum
Hi everyone, As currently drafted,  the 2020 Chinese Pharmacopeia, the benchmark publication on the safety and efficacy of pharmaceuticals legally available in China, includes 319 new entries. The publication includes more than 5,500 traditional Chinese and Western medicines. The official compendium of the standards of purity, description, test, dosage, precaution, storage, and the strength for each drug legally marketed in China is published by the Chinese Pharmacopoeia Commission. It is designed [More]

Is data integrity music to your ears?  Ours, too!

ALCOA, GAMP, Part 11, GIGO, we cover it all.
(Sung to the tune of Simon and Garfunkel's "The Sound of Silence.")

Year in and year out, protocol deviations are the most common FDA Site Inspection finding. Why does this keep happening?

If you’ve seen FDA’s Inspectional Observation Summaries, you know that in 2015 the most frequently cited violation in clinical research by far was “failure to conduct research in accordance with the investigational plan.”  Do you know this finding also topped the list the year before that?  And the year before that?  In fact, deviating from the protocol has been the most common observation every year for the last decade.

Why does this keep happening?



The Nature of Protocols
This will come as a surprise to no one: not all protocols are well written.  Important procedures can be hidden in the most obscure places.  Charts depicting Time and Events Schedules are famous for carrying dozens of footnotes that appear nowhere else in the protocol, yet convey important study procedures.   For instance, a pre-dosing column may include a footnote that provides a timeframe for performing a physical exam; a post-dosing footnote might specify the interval at which vitals must be taken.   Failing to follow study procedures compromises subject safety and data integrity; FDA won’t care whether the procedures were in big bold italics or 7-point font.

This, too, may come as no surprise, but not all protocols are error-free.   Information in charts may not match the narrative.  Procedures in Section A may conflict with procedures in Section B.  When the FDA investigator spots an inconsistency, you’ll be asked which of the two conflicting procedures you followed and why.  If you performed procedure A only because you didn’t even notice there was a B, it will be clear you didn’t read the protocol as thoroughly as you needed to.  The FDA investigator may become concerned that your study execution differed from the sponsor’s intention.  This is not a concern you want to trigger.

For these reasons, it’s imperative that study staff read and understand the protocol.  Study team members need to ask questions about anything they’re unsure of, seek clarification on protocol inconsistencies, and get responses that satisfy before starting the study.   A PowerPoint overview is not sufficient training.

One more irksome attribute of protocols that can make them difficult to follow -- they change.  While most study sites allocate time and resources for initial protocol training, many lack a plan for training staff on protocol amendments.   A disproportionate number of protocol deviations occur in amended procedures, and it’s often because staff members have been insufficiently trained on them.  (And when you do train on protocol amendments, don’t forget to document it.)

Deviation Temptation
A protocol is not a suggestion; PIs cannot substitute their own judgment for prescribed procedures, no matter how well-intentioned the departure.  The protocol for a psoriasis study might call for the PI to perform a series of punch biopsies, very invasive procedures.  After the first biopsy, an empathetic PI might be tempted to skip a second if he observes the plaque is clearing up; the drug is working.  But this would be a protocol deviation.  The protocol for another study might preclude the use of a particular drug, even though the drug is routinely used throughout the practice to treat a symptom that a study participant is exhibiting.  But the study protocol trumps standard of care; prescribing the drug would be a protocol deviation.

A PI who feels she must deviate from the protocol for some reason must obtain prior approval, since failure to follow the protocol can jeopardize the reliability of the study data, if not subject rights and safety.



Deviations Happen
So you’ve thoroughly read the protocol, you’ve asked your questions and received the necessary clarifications, you’ve trained your staff on the protocol and its amendments, and you do your best to follow them.

Despite all your preparation and vigilance, protocol deviations happen.  They just do.  And when they do, here are two don'ts.

(1) Don’t panic.

(2) Don’t let an FDA investigator find them first.
Take the time to fully document any protocol deviations.  Be sure to record why they happened, how they were corrected, and what was submitted to the IRB.

[Note: IRBs have different requirements about what types of protocol deviations should be communicated.  Out-of-window visits are common and are frequently considered too minor to report.  But nothing’s black and white.  If the missed visit resulted in missed doses, that would probably change the calculus. The PI needs to determine whether to notify the IRB, and if no submission is thought necessary, it’s a good idea to document why not.]

_______________________________________________________________

A version of this article originally appeared in InSite, the Journal of the Society for Clinical Research Sites.

Over the years, attendees of MAGI Clinical Research Conferences have collected a set of practical, actionable suggestions for improving clinical trials. More than eighty such tips appear in the July 2019 edition of Journal of Clinical Research Best Practices*.  In this post, Polaris auditors weigh in on some of their favorite MAGI suggestions. Surprising no one, they also were eager to share some of their own.

Our Favorites Tips from MAGI

So how does a clinical trial tip earn a spot on our exalted Faves List?  First, it must be something we don’t see too often, or not as much as we’d like.(If most organizations already do a useful thing, it doesn’t really qualify as a helpful tip; it’s really just a common practice.) Second, the effort to implement the tip can’t be too onerous. If a practice requires too much interdepartmental coordination, change management, training, money, or resources, it’s not a tip. It’s a full-blown initiative.

So here they are. Each tip from MAGI attendees is in bold font. Our accompanying commentary is in plain text:

• To help ensure quality study conduct, clinical sites should prepare protocol-specific quality checklists for each study. We’ve written about quality checklists from the auditing perspective before. They’re not a panacea, certainly, but that doesn’t mean they can’t be very useful.
  
  
• After study close-out, sponsors and CROs should consider holding conference calls with groups of sites to capture lessons learned. This in turn could be used to improve training, SOPs, SIVs, etc.
  
  
• As a recruitment aid, clinical sites should create pocket-sized, laminated study cards that list the inclusion/exclusion criteria for a study.  Site staff members can keep these cards in their lab coat pockets and quickly refer to them when treating a patient who could be a potential subject.
  
  
• CROs should share risk assessments and mitigation plans with Sponsors. We agree, but would also encourage CROs to keep the sites involved and aware of risks so they can anticipate them and proceed accordingly.
  
  
• Sponsors/CROs should ensure proper qualifications of vendors prior to executing contracts. It’s hard to argue with this logic, but we don’t see it as much as we should. Too often qualification audits come after the paperwork has been signed. Should the audit uncover noncompliance or quality risks at the vendor site, it’s much harder to get the vendor to make necessary changes after the contract is in place.
  
  
• CROs should align 3rd party contracts with the Sponsor/CRO contract and the Clinical Trial Agreement. Yep.

Additional Tips from Polaris QA/Compliance Auditors

The MAGI list of clinical trial tips brought others to mind that we wanted to share. We applied the same criteria to these suggestions as we did to the MAGI contributions: (1) not necessarily rare, but not as common as it could be, and (2) not overly complex or expensive to implement.

• When evaluating outsourcing partners and clinical sites, Sponsors and CROs should make sure to look at personnel turnover rates. Frequent turnovers may suggest underlying problems that could jeopardize study conduct and quality.
  
  
• Sponsors and CROs should make sure their Monitoring Report templates are consistent with the Clinical Monitoring Plan (CMP). For example:
  
  
• The CMP calls for a focus on a particular set of critical variables, but the report template only has a place for recording that 100% SDV was completed. This means that there’s no way to document that the monitor put special emphasis on anything.
• The CMP requires bi-direction review of study data – a confirmation that what is in the CRF can be verified in the source, and all pertinent data in the source can be found in the CRF – but the report template only allows for the former to be documented.
  
  
• Every member of the site team has valuable input. It’s important to include the study PI, CRC, pharmacist, and other key personnel in the discussions. In 2017, we wrote an article about the important, yet often overlooked, input that the pharmacist on site can provide.
  
  
• There are many reasons that trial participants leave a study, many of which can’t be remedied with improved site practices. But sites that demonstrate they value the participation of their study volunteers, and honor the time they’re spending and contribution they’re making, tend to have better retention results. To that end:
  
  
• To help participants schedule their time, sites can prepare calendars that include all study visit dates and indicate the activities and procedures they entail. (This, of course, needs to be approved by the IRB).
• When participants arrive, they shouldn’t have to sit in a waiting room or empty exam room; they should be seen immediately so they don’t feel their time is being wasted.
• Sites can provide beverages and light snacks to their study participants who especially appreciate them immediately after a fasting blood draw (protocol permitting, naturally). It’s a small courtesy, and not difficult to do. Whose day isn’t brightened by a proffered nosh?**

Uh oh. Now we got you all thinking about mini muffins and cheddar popcorn. Go ahead. Grab a treat. We'll talk later.

________________________________________________________________
 * Journal of Clinical Research Best Practices, July 2019

** Proffered Nosh™ would be a really great name for a restaurant. Or a fictional Scotland Yard Inspector -- legendary for his wit, brilliance, wine pairings, and fashion sense.