Clinical Trial Tips: Practical and Actionable

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.

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 * 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.

Optimizing Outsourcing Options for Small Sponsors

What can small sponsors do to secure the outsourcing resources they need as large CROs form strategic alliances with Big Pharma?

Partenships between large pharmaceutical companies and large CROs have become the norm.  The advantages for sponsor companies include shared risk, knowledge transfer, dedicated resources, shorter time to market, and the ability to implement the massive data integration that clinical development requires.  Strategic alliances are arguably as advantageous for their outsourcing partners, providing a steady pipeline of work that’s larger in scope and longer in duration than is typical under traditional arrangements.

Strategic Partnerships in Big Pharma: Implications for Small and Mid-sized Sponsors

Traditionally, large biopharmaceutical companies have outsourced clinical study responsibilities to a wide variety of external vendors, distributing the work across many service providers.  For their part, large CROs have routinely provided services to both large and small biopharmaceutical companies to keep their top-notch resources utilized to capacity and add to their bottom line.

Over the past several years, large sponsors and CROs have been trading in these transactional, fee-for-service business relationships for longer-term, tightly-integrated strategic partnerships.  And the trend is only accelerating.

What Trend in Big Pharma Means To Smaller Industry Players

There’s been a shift lately in the way Big Pharma is doing business.  Traditionally, large pharmaceutical companies would outsource clinical study responsibilities to a wide variety of external vendors, essentially distributing the work across many service providers.  Large CROs routinely performed work for both large and small pharmaceutical companies to keep their top-notch resources utilized to capacity and add to their bottom line.

More recently, economic pressures have moved Big Pharma away from transaction-based, fee for service arrangements with their CROs, and towards strategic alliances with them.  The advantages for sponsor companies are many: shared risk, knowledge transfer, and shorter time to market.  Strategic alliances are arguably as advantageous for the CROs, providing a steady pipeline of work that’s larger in scope and longer in duration than is typical under traditional arrangements.  The industry journals are replete with sage warnings about culture incompatibilities and intellectual property protection, but done correctly, there may be few significant downsides to these strategic alliances.

As is frequently the case, a new advantage for one segment of the industry is a new disadvantage for another.  Small and medium-sized pharmaceutical companies, like their large counterparts, have been feeling the strain of higher costs and smaller staffs.  Adding to these economic pressures, the trend towards alliances among the large players increases competition for top-drawer CRO resources. The reduced availability of these outsourcing options likely means smaller sponsor companies will pay higher prices for services.  It could also mean that at the same time they are paying more, the quality of service and level of commitment they receive may be reduced, as the best and most experienced CRO staff members are dedicated to projects associated with strategic alliances.

Just as Big Pharma has taken a look at the economic environment and has begun forming nontraditional business relationships, small and medium-sized should take stock and make some adjustments, as well.  They should begin looking beyond their traditional outsourcing choices and consider selecting smaller outsourcing partners who may well be in a better position to focus on individual projects and give priority to shorter term engagements.  After all, a project that’s small to a big CRO will be comparatively big to a small CRO.

Effective vendor prequalification has always been important, yet this new environment may elevate its priority.  If small and medium-sized sponsors look to expand their set of outsourcing partners, they will need to increase both the time and resources they currently invest in prequalification activities.  To further ensure that potential new service providers have the ability to deliver quality and timely results, companies may increasingly opt to engage third-party consultants to perform additional prequalification audits or to develop comprehensive in-house vendor qualification programs.

Bottom line:  The trend toward strategic alliances among large companies will change the terrain for many industry players; competition for the services of large, established CROs is likely to increase.   Smaller sponsor companies can compensate by emphasizing vendor prequalification procedures and subsequently contracting with capable, smaller services providers.

Expert consultants at Polaris would be happy to talk to you about any CRO prequalification needs you may have.  Contact us at info@polarisconsultants.com or visit our website at www.polarisconsultants.com.

by Laurie Meehan

This blog discusses trends and issues in the pharmaceutical and dietary supplement industries.  Click the SIGN UP link to subscribe to occasional notifications of new blog posts.