The Laszlo Letter

IT Trends for 2012 by SAFE-BioPharma

The following was recently released by the SAFE-BioPharma Association. Although the IT trends they cite may be on the adoption curve, it is not clear how long the adoption will take. As with almost anything in our industry, don't expect it to happen overnight.

THREE MAJOR IT TRENDS WILL SHAPE LIFE SCIENCES IN 2012

Fort Lee, NJ (January 19, 2012) -- Three trends will shape the life sciences in 2012, according to an analysis by SAFE-BioPharma Association. They are the expanded use of standards-based interoperable digital identities, cloud computing in clinical trials, and the use of electronic trial master files for clinical trial management.

1. STANDARDS-BASED INTEROPERABLE DIGITAL IDENTITIES

Industry leaders are rapidly increasing use of these unique digital identities among employees, collaborators, and clinical investigators. Issued once every three years, they take the place of multiple on line identities and can be used to control access to information and physical facilities. They also provide the ability to apply legally-binding digital signatures to electronic documents. The benefit of interoperability is that the digital identity is recognized and accepted by US government agencies, by other companies [broken sentence]

2. CLOUD COMPUTING IN CLINICAL TRIALS

As demonstrated in a study between the National Cancer Institute and company-based cancer researchers, significant time and cost savings are realized when trial-related documents are accessed from the cloud rather than delivered by courier or mail. Interoperable digital identities (NCI researchers using government provided digital credentials; company researchers using SAFE-BioPharma digital credentials) give researchers access to the cloud-based electronic documents as well as the capability to apply legally-binding digital signatures.

3. ELECTRONIC TRIAL MASTER FILES

“Trial Master Files – the central record containing the files associated with clinical trials – are one of the last areas where clinical development records are primarily paper-based,” explains Mollie Shields-Uehling, president and CEO, SAFE-BioPharma Association, Multiple pilot studies scheduled to start in the next few months indicate that pharmaceutical companies are preparing to make the process electronic. Companies will use SAFE-BioPharma digital identities to manage access to documents and to provide participants with the ability to apply legally-binding digital signatures.

The global SAFE-BioPharma digital identity and digital signature standard is used throughout the biopharmaceutical and healthcare communities to meet specific security and confidentiality needs. It was created with participation from the US Food and Drug Administration and the European Medicines Agency. The standard and its ongoing development is managed by SAFE-BioPharma Association, a non-profit supported by its members. For more information visit http://www.safe-biopharma.org.

R&D - The need for accountability. Pfizer weighs in again.

 
Matthew Herper of Forbes magazine wrote a review of a press conference held by Ian Read, the new CEO of Pfizer. Of interest to me was the following paragraph:

"One of the main goals of the changes is to try and prevent any repeat of Pfizer’s disastrous investment in Exubera, the inhaled insulin, which the company spent years developing before it hit the market and bombed. Without accountability, Read says, projects were handed off from one team to the next without demands that they actually be ready. 'You get the transfer from one stage to the next stage, always investing in hope rather than strong clarity of signals and clarity of medicine and clarity of mechanism.'"

While I continue to fault Pfizer for their lack of imagination when it comes to R&D, this statement is right on.

Some of you may have read my point of view on the Exubera debacle on this web site. Mr. Read seems to understand that once a project takes on a life of its own within the R&D pipeline it is nearly impossible to stop it.

Why is this the case? Because pharmaceutical firms have gotten so specialized and compartmentilized that people are simply completing the work assigned to them without seeing the big picture. It seems that even Lifecycle Teams are not able to complete a holistic review of a drug candidate. The stakeholders are simply focusing on getting their part of the work done right and on time and are rewarded for doing so. If the incentives are not based on team success then the chances of getting a compound on the market are significantly reduced. This is where the idea of accountability comes in and was highlighted by Mr. Read.

Now, Mr. Read's observation is not original. We have heard many times about the need to "fail early." Unfortunately, the acceptance of failure and the possibility of being rewarded for it has not really become a visceral behavior at most companies. Perhaps Mr. Read will take steps that will make this happen at Pfizer. If that happens others are sure to follow.

 

Are clinical trial results all wrong?

And what to do about it if it's true.

One would not normally consult the New Yorker magazine about the scientific method, but a recent article in that publication makes it necessary that we do just that.

In short, this article concludes that most of the controlled clinical trials that have been performed and used to get medical treatments on the market had (and will continue to have) false results.

Now, read that again and let it sink in!

Since we have learned to be paranoid about the integrity of what we do in this industry, it would be natural to think that this claim must be based on evidence that the studies have been rigged. This is not the case. Rather, the various individuals cited in the article claim that it's simply human nature that leads us to reach the results that we wish to reach and that we actually use the scientific method to help us get there.

Now, it's not my objective to summarize or rehash what's in this article. You are perfectly capable of doing that yourself. Rather, I want to share with you my ideas on the ramifications of the core finding of the article. Let me repeat those here in my own words:

1. It is nearly impossible to come up with a truly objective scientific study design;
2. It is human nature to (unknowingly) design the study to prove what we wish to prove;
3. We use scientific tools and techniques to fool ourselves that we are being objective;
4. We do this all with good intentions (most of the time); and
5. Other scientists reproduce the false results for the same reasons (see 1 - 4)

If we take all of this at face value, we would need to ask why we continue to design and run controlled clinical trials. Of course, we know that this is what the regulators (i.e. FDA, EMEA) want. Since the regulators are not necessarily smarter than the sponsor's scientific staff or, for that matter, the experts that they call on to pass judgment on marketing submissions, we need to conclude that everyone pretty much has deep faith in the current and accepted methods we use to carry out these trials. Based on this article, we thus need to also conclude that all of these people are wrong!

At this point, you may ask yourself "What is this guy talking about? He must be an idiot!" If you think this, it means that you have not yet read the article (see link above.)

Personally, I found this article to be quite disturbing. After reading it, I could have done one of two things: 1. Put my head in the sand and pretend that I never read it; or 2. Bring it to your attention to give the claims more visibility and lead to its evaluation by our industry as a whole.

Now for the good news:

If we can accept the hypothesis and the evidence presented that it's inevitable that the results of clinical trials are normally false, we can move on to a few ideas that may help get past this problem. Here are the ones that I have formulated:

1. Continue to design and execute controlled trials but strictly limit the number of them required to gain marketing authorization;
2. For the trials that remain, focus primarily on safety and less so on efficacy;
3. Allow for adaptive study design for Phase II and III studies;
4. Provide marketing authorization earlier for the claimed indication;
5. Require rigorous follow-up of the actual patient population receiving the treatment including the analysis and reporting of pooled data;
6. Require the reporting of outcomes to show both safety and efficacy in the actual patient population;
7. Over time, allow outcomes from different treatments to determine whether a drug stays on the market and/or ascertain its cost/benefit value to society

Does any of this sound familiar? The answer is yes. It's just that we now have even more reason to do it.

 

Software for Clinical Development - 2011 Edition

It's finally here!

The 2011 edition of Software for Clinical Development is now available and it's still FREE.

Download 2011-ClinDevSoftware-LaszloLetter.

As before, this comprehensive guide comes to you as an MS Excel spreadsheet so you can slice and dice it any way you wish. Over 200 solutions from 95 vendors are represented and categorized by solution area. The following pie-chart will give you a pretty good feel for this.

 
Most of the acronyms should be pretty familiar to you. If you don't know some of them, it's likely that you have no interest in that category anyway. But, there are a couple that may be unfamiliar to most of you: 

RIMS - Regulatory Information Management System

MIMS - Medical Information Management System

Of course, a glossary defining all of the acronyms is included in the spreadsheet.

As you would expect, over 50% of the solutions come from just 5 categories:

• EDC - Electronic Data Capture
• CTMS - Clinical Trial Management
• ePRO - Patient Reported Outcomes
• CDM - Clinical Data Management
• IVRS - Interactive Voice Response

What's more interesting are the emerging software categories that include:

• Data Analysis
• RIMS - Regulatory Information Management
• CDW/CDR/SCE - Clinical Data Warehousing/Repository and Statistical Computing Environment
• Patient Recruitment

Hidden Gold Nuggets: Pfizer's Progress in Drug Development

I continue to be amazed by the number of great articles that do not get enough exposure. The key reason is that they are trapped in specific publications that you may never see or even know exist.

I was reminded of this again when opening my latest copy of 'Pharmaceutical Outsourcing' magazine. In this October 2010 issue I ran across an article by Chris Hilton of Pfizer, giving a great summary of the work being done by its Development Operations group.

As you may imagine, a significant part of the article focuses on Pfizer's growing and greater reliance on outsourcing. For example, the article states that in the past 5 to 7 years, the number of internal staff performing such functions like monitoring, data management and clinical programming has dropped from about 3,000 to 400 [no, this is not a typo].

At the same time, the number of external colleagues has gone up from roughly 100 to 2,400, most working for a group of 20 CRO's.

Doing some simple math got me to conclude that the total number of workers has stayed about the same. Of course, I don't know what is really going on here and one would need to ask the author what is behind the numbers. For example, are more studies being done by fewer people? Did the types of work being done change in any significant way? To what extent are technologies used affecting staffing?

Some other interesting facts (gold nuggets) noted in the article are:

• Year after year, the Last Patient Last Visit (LPLV) to Database Release time interval continues to drop
• The number of days from database lock to final CSR has dropped from 200 to 80 days.
• 1.2 databases are locked each day
• Reduction in cycle times ranging from 39% to >60% in several trial processes like Clinical Study Report completion and Protocol Development

 It is not my intention to review the whole article here. The best would be for you to read the whole thing and learn about other practices at Pfizer such as Functional Service Provider use, Reverse Auction Process, Continuous Improvement, Optimized Monitoring and Lean Six Sigma.

Read It! You won't be disappointed.

 

Update: Software for Clinical Development - 2010 Edition

The updating of this software list is still in progress. Several new software categories have been added and the list of vendors is growing and shrinking at the same time. In other words, some companies have gone out of business, others have been assimilated and new ones have also been born. At the moment, I am optimistic that the list will be ready to share sometime in November. Your patience is appreciated and hopefully rewarded fairly soon. 

DIA 4th Annual Clinical Forum - Lisbon - October 11-13, 2010

  
If you are in Lisbon next week, chances are that you will be there for this conference.

This note is just to let you know that I will be there and presenting on a panel related to Clinical Data Warehousing chaired by Peter Stokman of MSD. This will be a 90 minute session focusing on the practical aspects of implementing systems that manage and allow for the analysis of clinical data with full traceability and auditability.

The rest of the program looks great with no less than 40 topics covered over the three days. Check out the program here.

If you'd like to get together and chat about any topic of interest, just drop me a line at my email address.

See you there!

Software for Clinical Development - 2009 Edition

Many of you have written to me over the past year that the MS Excel spreadsheet I created last year that listed software for clinical development was very useful.

Some people also wrote in that the list was by no means complete. Of course, they also told me which software packages were missing.

So, without further ado, here is an up-to-date list for 2009. Of course, I expect that several readers will again let me know that it's still not complete!

Download ClinDevSoftwareVendors-2009

The High Cost of Swimming Upstream with IT Projects

Setting the scope of an IT project is possibly the most important factor affecting it's chance for success or failure. While most project do end up delivering some benefits, they rarely deliver everything that was hoped for.

Even when projects succeed, we may still be left clueless about unintended consequences. This is the main point of an article I recently wrote in the June issue of Pharmaceutical Executive Europe called "The High Cost of Swimming Upstream."

Just click on the title to see the article.

Software for Clinical Development

Having recently particiapted in two DIA meetings, I thought it would be useful to pull together a spreadsheet of vendors offering software used in clinical development. This can serve as the basis for a more comprehensive list built and maintained by reader input.

For now, the list is kept in an Excel spreadsheet:

Download ClinDevSoftwareVendors-April2008.xls

Please note that I consider this spreadsheet as the intellectual property of The Laszlo Letter. In other words, it is copyrighted. You may use it as a reference document but not benefit from it in any financial manner or reproduce it without my permission.

To contribute new items or update those that already exist, just use the comment function of the blog. I will take it from there and post new versions of the spreadsheet as necessary.

Thanks in advance for your help.