Topic 18 – Site Payments in Phase 4 Clinical Trials

(Full Disclosure – I was introduced to this issue by my client who has a interest in the solution to the problem but regardless I believe this to be a real problem. )

As P4 clinical trials grow larger and more complex, the challenge of site payment computation and accrual grows as an issue.

As more and more sites become sophisticated partners in clinical trials they are demanding customized contracts with payment terms associated with their work and cash flow needs.  It is hard to blame them when pharma and CROs has been so bad about paying, many times paying sites over 90 days after the site incurs the cost and paying inaccurately.

Payments are a source of friction with PIs and thus KOLs.

CenterWatch has identified late payments as the #1 site concern about pharma for the last three years. For a P4 study, Principle Investigators (PIs) are often key opinion leaders (KOLs), since many of KOLs have access to the type of patients needed for the trial.  Developing a strong scientific dialog with KOLs is a fundamental role of MA.  Yet, at the same time we are working so hard to establish a positive working environment to collaborate with KOLs, we are also degrading that relationship due to late or inaccurate study payments.

It is not at all unusual for an MSL to receive complaints about late payments on trials, even though the company has outsourced the trial to a CRO for payments.  The PIs will hold the company responsible despite the CRO’s involvement.

Payments are a source of regulatory risk.

Since payments are generally computed manually even by most CROs, many mistakes are made.  Thus at the end of each study there is a process called “End of Trial Reconciliation” when the actual amounts owed are computed against the final data collected.  Any missing money (and there is often hundreds of thousands in overdue money) is paid at this point.

BUT, the regulatory risk is not in delayed payment.  The regulatory risk is what happens if we find we have paid too much.  This happens often in clinical trials because due patients drop out but due to computational errors the site still receives payments for that patient.  If that occurs we have overpaid the site and the PI (which we discussed are also KOLs).  But this computation error may be from years before.

Now the quandary is – do we demand repayment from the site for our error.  Technically, the site should refund the overpayment.  But, I would ask your operations group if you have ever asked for that money back.  My practical experience is that the overpayments are rarely if ever collected back.  If they are not collected back, we have essentially paid more for the trial than fair market value and thus we have a potential compliance issues.

While this issue has not been one I have seen enforced to date, given the growing scrutiny on all payments to physicians with the Sunshine Act, I think it would be wise to ensure that this risk is avoided.

Payment computation is a hidden cost. 

With these more sophisticated contracts comes the need to administer them and compute payments.  Sites don’t send an invoice.  So, determining the amount to pay is left up completely to the pharma company.  Performing that computation can be complex and time consuming.

Since many pharma companies outsource their P4 trials, what they are doing is paying the CRO to perform this computation for them.  In some larger P4 trials, hundreds of thousands of dollars in fees are spent for the CRO to compute and issue payments.

New solutions are available.

The good news is that a new type of software is being developed to automate the payment process and avoid the need to do any manual calculations.  If you are interested check them out .  My client is www.clinverse.com.  Also their competitor is www.greenphire.com.

What has been your experience with P4 site payments?  Leave your thoughts in the comments.

QuickNote: The Sunshine Act is Here to Stay!

Given the results of the presidential election, the remaining hopes I have heard expressed that the Sunshine Act would not be implemented should have evaporated.

We have already discussed here some immediate work MA needs to do to start prepping the ground for the data.  While it is looking likely that implementation may be delayed, MA leaders should be planning for this in their 2013 budgets.

Any other impacts of the election that MA leaders should consider?  Leave your thoughts in the comments.

Topic 17 – New MA Organization – MedComm/SciComm

A reader and I discussed her dilemma the other day.  She was being tapped to create a new MA function for a small biotech that was bringing its first product to market.  She had fairly broad latitude but was not sure where to begin.  Some of the points of our discussion are captured below.

We have already discussed preparing an MA team for launch here, the effective way to manage MSL groups here  and the best way to develop a MedInfo function here, I thought I would focus on the Medical Communications or Scientific Communication group with this post.  A note about function names.  I very much prefer the term Scientific Communication because it more correctly reflects the role of the function which is to provide scientific data to the market place some of which is purely medical but some of which may be of a health economic nature that are not purely medical.

SciComm is a critical function for MA but developing one from scratch is as much a challenge in internal politics as a challenge in terms of operations.  At a small company, before there is a SciComm group the company is already publishing.  So, developing a group can be sensitive and many toes can be treaded upon if one is not careful.  The best approach is to co-opt the staff that have been driving the publication efforts in designing (and maybe leading) the new SciComm function.  But, it is critical that everyone involved realize that publications take on a broader role in SciComm than they did in CD.

In CD the role of publication was primarily focused on the results of clinical trials.  That continues to be a responsibility of SciComm but its role of sharing scientific data expands to identifying the scientific questions that the marketplace needs answered, some of which will be answered through literature analysis or through non-clinical studies.

Given that CD is typically handling the publications in advance of the SciComm function, the temptation may be to put developing the group on the back burner until other MA functions have been more fully developed.  This would be a mistake.  SciComm needs to be analyzing the scientific needs of the HCP community and ensuring that the required scientific information is available concurrently with launch.  Any delays can result in a vacuum of information and who knows what will fill that vacuum (or which competitors will try to fill that vacuum).  So, at least 18 months prior to the launch the SciComm group should be launched, right along side the MSL function.

What has been your experience with SciComm groups at launch?  Leave a comment.

Topic16: Greater Clinical Trial Transparency and Medical Affairs Rapid Response

GSK announced this week that it would open up its clinical trial data sets to researches who receive approval from a GSK review board.  Next year, the EMA intends to open up access to all new clinical data files that are part of a product registration filing.

I believe this is a trend that will not stop – the increasing openness of biopharma with its clinical trial data.  What does this mean for medical affairs?  I have some initial thoughts below but I would be curious to hear your perspective.

As this data becomes more open, other scientists, some perhaps not fully qualified to understand the data set, are going to review it and draw conclusions.  Since our culture has incentives for publicity in academia, expect that at least some of the scientists are going to spin the data into the scariest sounding headline they can.

The result is, I predict, a sharp rise in news stories highlighting safety risks of products, often blown out of proportion.  Nevertheless, it will ultimately fall to MA to deal with this misinformation on the scientific side.   While this can happen today, it is still fairly rare.  I believe it is going to be common place.

In order to be ahead of this, MA leaders are going to need to set up a Rapid Scientific Response capability (if they don’t already have one):

• Identify Potential Areas Requiring Responses  –  First step is determining what potential areas require rapid scientific responses.  Start with a brainstorming exercise and prioritize to get to the top 5 to 10 topics.


• Determine Leader of Response – For each topic area, identify who from the MA or other functions team should take the lead on coordinating the rapid scientific response


• Identify Internal Experts and Voices – Search through the organization and determine who else has the scientific expertise and other skill sets needed to support the rapid scientific response – PR and Legal should be a part of each team


• Develop Rapid Response Plan – Create a plan for assessing the situation, determining the outline of the response, assigning elements to team members, pulling it together, getting it reviewed and getting the message out  

The entire goal of develop the Rapid Scientific Response capability is to be able to move quickly when the event occurs and produce an accurate and complete response in as little time as possible.  Without this advanced planning, when issues hit no one is clear who should be taking the lead and how.

Do you have a plan for Rapid Scientific Response?  What other impacts do you think the increasing openness of clinical trial data will bring to MA?  Leave your thoughts in the comments section.

Topic15: OLIS and Journal Clubs and Journal Articles

I was talking with a friend and client about internal journal clubs in particular and discussing journal articles with HCPs in general. This discussion may be germane to a number of you because it really stems from what I think of as “Overactive Legal Imagination Syndrome.”

OLIS is the reality many of my clients face when their legal group begins to tie itself in knots over the practical implications of the fact that MA must talk about the science involved with its products, and some of that science may ultimately be compelling enough that the HCP decides that our product is something that they should use.  OLIS drives them to wonder “How can we not be promotional if the results of our permissible scientific exchange is that the HCP decides to use our products?”

See our thoughts below:

1)      Can we allow Internal Journal Clubs?

• We already agree that field staff can have permissible scientific exchanges with physicians


• In order to have scientific exchanges they need to know the latest science which is represented by what is being published in peer reviewed journals


• Although our team is good, no one member of the field force has all the knowledge necessary to understand the huge range of potential scientific articles or the time to cover the huge range of journals


• As a group, however, they do posses both the knowledge and the time


• Therefore, they should be allowed to review the new scientific information as a group and share with the members the information they need

2)      What if the conclusions reached in the internal discussions of the articles are biased?

• So what? – we are not going out to the HCPs to present our conclusions but to have a scientific dialog – to listen and answer scientific questions


• Any perspective we have is already perceived to be biased – we work for a major pharmaceutical company and everyone knows it


• The issue is not bias – which is not against the law – the issue is promotion

3)      What if our perspective is deemed to be promotional?

• There is absolutely nothing new about a concern that our scientific dialogs run the risk of being promotional


• BUT, we already have standards and training in place to ensure our staff does not promote during scientific exchange – regardless of whether that exchange is about a new article in a journal or an existing safety issue, etc. etc.

4)      What if the conclusions of the author of the journal article are promotional in and of themselves?

• First, we need to agree that facts, even facts that are favorable to our products, are neither promotional nor non-promotional – facts are facts


• Conclusions drawn from the facts can be promotional


• So if the study finds that patients using our drug have better results than patients using a competitive drug, that fact is NOT promotional UNLESS our field staff says something like:

i.     “I don’t see  how anyone can read this and not put all their patients on our drug”

ii.     “Clearly our drug is the more effective and it wouldn’t be ethical to put your patients on any other treatment”

• If the author of the article draws their own conclusion “…and in the opinion of the authors you would be a fool to treat with anything but X.” then we are back to the points in number 3 above, meaning our team needs to know a promotional statement when it sees it and avoid repeating it


• In this scenario, the internal journal club is actually of value to the company because it allows the group to identify this potentially promotional author conclusions and agree on strategies to engage in this topic without endorsing the author’s conclusions


• Bottom line – these “promotional conclusions” drawn by independent 3^rd parties and published in peer reviewed journals are out in the public sphere and keeping our field team from understanding the article and agreeing on an approach to addressing it without a promotional bias will not stop HCPs from asking them about it and forcing some kind of reply

What has been your experience with OLIS?  What about internal journal clubs?  Leave a comment.

Slightly OffTopic: NEJM Article on BioPharma Research Credibility

Have you seen this special article in the NEJM entitled: A Randomized Study of How Physicians Interpret Research Funding Disclosures.  It is disturbing reading for all of us in the industry, including MA.

In the study, researchers presented 503 board-certified internists with three random studies with a high, medium and low level of methodological rigor.  And then randomly assigned each study one of three funding sources: NIH, Biopharma Industry, Not Disclosed.

The good news is that respondents generally assigned stronger credibility to studies with stronger methodologies.

The difficult news is that the internists believed the results of industry-sponsored were less credible than those that were NIH funded and with no funding disclosed.  And that results remained the same whether the study was of high rigor or low rigor.  Since the funding source was randomly assigned its clear that simply associating industry funding reduced credibility.

And the kicker – over 75% of the respondents accept support from industry in some manner, so these are not a bunch of ivory tower purists throwing stones.  These are exactly the people that MA needs to educate and these are exactly the kinds of studies that we use for that education.  Clearly we have a problem.

In an editorial that accompanies the study entitled Believe the Data, Dr. Jeffery Drazen suggests that physicians need to focus on the data and the rigor of developing that data.  As an industry, we need to echo that exact point.

We know where this skepticism comes from - too many newspaper stories of incomplete study disclosures, too many studies that seemed to lack rigor, too much willingness to spin results.

We cannot ignore this issue.  We need to hit it head on – discussing this now proven bias and why it should not impact the interpretation of results for a given study due to its rigor, etc.

Something that many of us have suspected for awhile, that industry science was being discounted simply because of funding, is now shown to be true.  We must address it openly because like any bias when it is pointed out to people they are less likely to be prey to it.

What do you think we can do to address anti-industry bias?  Leave your thoughts in the comments section.

Topic14: SOPs in MA

Now for a topic no one wants to talk about but everyone should become more familiar with – Standard Operating Procedures.  The hard truth of today’s world is that SOPs are no longer optional for MA.  In fact, SOPs are critical for success in today’s global MA.  In this post, I will discuss SOPs in general as well as share some do’s and don’ts for developing effective MA SOPs.

Our brethren in Clinical Development have been living in a world of SOPs for much longer than MA because their work was more explicitly regulated.  When you are regularly audited by agencies looking for an excuse to delay the marketing of your next blockbuster, you are highly motivated to have whatever documentation they are looking for.  And, in CD, that means SOPs that clearly demonstrate that all clinical trials are conducted following GCP and other related standards.

In MA we used to be less concerned about regulation enforcement, but those days are over.  So, what is the state of MA’s SOPs?  If your environment is like those in my experience, the answer is a mixed bag.  Many organizations have some good SOPs but few organizations would claim their SOPs are simultaneously:

1. Complete


2. Accurate


3. Trained and understood by the relevant staff


4. Consistently updated

Most MA leaders will tell you it’s important and on the organizational To Do list but it rarely seems to rise up to the top of that list and almost nothing below number 3 on that list can get addressed in any given year.

Yet SOPs represent one of the very best defenses any organization has to arguments that it is operating contra to regulations.  By having clearly defined processes that are compliant, a training program to show that people learned and understood those processes and a program to ensure that those SOPs remain updated, the organization has a very strong argument in its favor, even if a single actor is caught performing incorrectly, the argument can be made that it is a single bad actor not an institutional problem.

But SOPs are not just defensive in nature.  When well done, SOPs represent an opportunity to capture best practice and apply that best practice on a global level.  Every country, every region does not need to re-invent the wheel.  What we do in MA is standard enough that we should be able to build a single optimized approach that we can apply on a global basis.

When building SOPs there are some definite Do’s and Don’ts.

DO’S

• Leverage major disruptive changes to implement or enhance SOPs
  
  
  
  • SOPs are a major effort and often difficult to justify on their own (see To Do comment above)
  
  
  • Instead, leverage a new system implementation, new regulatory regime or other major change that seems to hit every year or two as the vehicle for investing in SOPs
  
  
  
  


• Be inclusive
  
  
  
  • Ensure to involve every function and every region that is affected by the SOPs, even those that are outside MA
  
  
  • Make sure the SOPs remain valuable throughout the globe if possible
  
  
  
  


• Develop MA-specific SOP templates and development processes
  
  
  
  • Trying to take the CD SOP development templates and processes can result in over engineered MA SOPs
  
  
  • MA SOPs don’t need to be as detailed or structured as CD SOPs because the goals are different in terms of regulatory support – CD SOPs need to comply with GCP at a minimum which drives a certain level of depth that is not necessarily required in MA
  
  
  
  


• Remember the Training
  
  
  
  • Training is the link between SOP development and real world value, yet many organizations fall down on this important step
  
  
  • SOP development efforts seem to lose steam after the creation effort and often result in training programs that fail to ensure that everyone who should learn does learn
  
  
  
  

DON’T

• Pave the Cow Path
  
  
  
  • Don’t just document the current process (cow path), instead take the opportunity of SOP development to do some process improvement work capturing best practices and defining new approaches
  
  
  • This may take a bit longer but the results are significantly more valuable
  
  
  
  


• Get Overly Complex
  
  
  
  • SOPs are guidelines not computer programs – the more detail the LESS valuable the SOPs can become as more and more real world situations don’t fit into the very specific processes
  
  
  
  


• Forget Certification
  
  
  
  • Its great to train, but in the future someone will question whether the training was effective – without some type of certification to prove understanding on the part of the trainees this is very difficult to prove
  
  
  • Certification does not, and should not, be onerous – just enough to prove that the key points are understood
  
  
  
  

SOPs in MA – not a topic anyone gets excited about tackling.  Yet, SOPs are going to grow increasingly important as the regulatory burden on MA grows.

What is your experience with MA SOPs?  Leave a comment and let me know!