A Guide to Understanding Clinical Trials

Recently, the Wall Street Journal partnered with Media Planet to focus on clinical trials in a feature in the New York Times. It looks a the progress that clinical trials have made over the past few centuries, patient perspectives, some of the ethical issues involved in clinical trials and much more. Find the insert here.

Partnerships Latin America Session Spotlight: Industry Update: Impact of the Economic Crisis and Industry Consolidation on the Global Development

Each week leading up to Partnerships in Clinical Trials Latin America, we'll be highlighting a session from the upcoming conference. It will take place August 2-4, 2010, in Buenos Aires, Argentina. For more information, visit our webpage to download the brochure.

Featured Session: Industry Update: Impact of the Economic Crisis and Industry Consolidation on the Global Development of Clinical Trials

Presented by: Victor Molina Viamonte, MD, FACC, President, CAOIC (Cámara Argentina de Organizaciones de Investigación Clínica)

About the session:
Low R&D productivity, increasing costs, and the impending patent expiration of blockbuster drugs have contributed to the recent wave of mergers, acquisitions, and corporate restructurings throughout the industry intended to reduce costs via consolidation and staff reductions. With budget restrictions in place, sponsors need to outsource more but with less money to do so and many are cutting back on development plans and delaying programs.

• The impact of consolidation and cost-cutting on clinical development
• Partnering with CROs to find innovative ways to get drugs to market spending less money and deliver molecules in a more productive way
• CRO strategy for growth in a marketplace where biotech is hurting and Big Pharma is scaling back• What will the global pharmaceutical industry look like in 5 years time?

Industry Alert: Official Call for Presenters: 2nd Annual Partnerships in Clinical Trials Asia Pacific

2nd Annual Partnerships in Clinical Trials Asia Pacific

October 5-7, 2010
Grand Copthorne Waterfront Hotel • Singapore

The premiere event for clinical development and outsourcing professionals to maximize efficiency and maintain quality of clinical trials in the Asia Pacific region

From: Lesly Atlas, Program Director, 2nd Annual Partnerships in Clinical Trials Asia Pacific
Re: Call for Speakers & Presentations
Event Date: October 5-7, 2010
Event Venue: Grand Copthorne Waterfront Hotel, Singapore

INDUSTRY ALERT: OFFICIAL CALL FOR PRESENTERS!
With the success of the Partnerships in Clinical Trials APAC launch in 2009, Partnerships is bringing its industry-leading speakers, unique combination of high-level strategic discussions and focused practical guidance, and unparalleled networking opportunities to the Asian-Pacific market for the second year running.

Partnerships in Clinical Trials APAC provides information you can implement immediately - from understanding the operational advantages of regional CROs to regulatory nuances across the region to the types of relationships working in Asian-Pacific markets.

To submit a session proposal or to express interest in joining the 2010 speaking faculty, email Program Director, Lesly Atlas at latlas@iirusa.com. The deadline to submit is May 12, 2010. Visit the Partnerships in Clinical Trails Asia Pacific Webpage here: http://bit.ly/cZUVv2

Submission Guidelines & Details
We are currently recruiting professionals in Clinical Operations, R&D, Strategic Sourcing, Project Management and Quality roles in the Pharmaceutical and Biotech industries who can share first-hand perspectives, insights, and real-world case studies on the focus areas below.

Partnerships in Clinical Trials APAC is now accepting proposals for case studies and thought-provoking panel discussions. In 2010, the event will address topics including:
• Clinical Trials in Asia Pacific – New Challenges and Opportunities
• Asia’s Pharma industry – Innovative Drug Development
• Review of the Regional Clinical Trials Regulatory Environment
• Repositioning Clinical Research – How to Face the Ethical Issues in Clinical Trials and Rebuild Public Trust
• Outsourcing to Asia – Combining Global Best Practices with Regional Experience to Meet Clinical Trial Requirements in Asia
• Finding the Right Partner for Your Trial Needs & Operational Aspects to Consider
• Strategies for Successful Site Evaluation and Selection
• Accelerating Patient Recruitment and Retention in Clinical Trials
• Assuring Project Excellence through Quality Staffing and Improved Communication Strategies
• Pharmacovigilance and Product Safety
• Improving Clinical Efficiencies through Proper Data Management
• Quality Assurance and Regulatory Compliance Tactics for Asia-Pacific Trials
• And more

Is your biggest challenge not addressed here? Contact Lesly Atlas to ensure that your pressing issue gets the attention it deserves!

For consideration, please e-mail latlas@iirusa.com with the following information no later than Friday, May 12, 2010.

• Proposed speaker name(s), job title(s), and company name(s)
• Contact information including address, telephone and fax numbers and e-mail
• Title and objective of presentation
• Summary of the talk
• What the audience will gain from your presentation (please list 3-5 key “take aways”)

NOTE: Due to the high volume of submissions, we are unable to respond to each submission. Those individuals chosen to participate will be notified by May 24, 2010.

REACHING AND INFLUENCING OUR AUDIENCE
To learn more about sponsorship opportunities, please contact: Andrew Sinetar at (646) 895-7340 or asinetar@iirusa.com.

Cancer is a highly complicated disease

Cancer is much more technically complex than many diseases and the understanding of how the biochemistry and the drug interact can make or break a product. The subject matter of the disease may make the oncologist ask millions of questions related to the disease. The primary difference between a cardiologist or a dermatologist may be that the they may ask only common/ routine questions to the pharma company responsible for marketing/ conducting the clinical trials of the drug, whereas the oncologist will ask a lot of why and where questions... why should I use this drug, where is the evidence to show X or Y etc. If the pharma company's drug isn't better than what an oncologist has already, especially in efficacy, no amount of hype is going to give you a hook or an advantage. Risk-benefit trade-offs in a serious disease that may lead to deaths forces people to think about the treatments in another light.

The most common questions an oncologist is going to hear from people who visit are:

Will I be cured?
Will it make me live a little longer?
Will the treatment make me feel better?

Success in the oncology arena boils down to data and how well a pharma company can stack up against the competition. Being first to market gives a pharma company , a huge advantage too, since a hurdle is set and the ones afterwards are forced to demonstrate why they are better.

http://www.blogs.veedaoncology.com/Lists/Posts/Post.aspx?ID=22

The world of competition

The world of competition
It's summertime here in India and same old rivalry has resurfaced- "Coca Cola Vs Pepsi"! It's been decades since these Cold drink giants are fighting over Indian beverage market share. Initially it was cold drink, but then the fight extended to other sections like energy drinks, healthy snacks, namkeens etc.


Trigger-
It started with Fanta's Holi ad for Coke, where Genelia De Souza was seen in a retro look. The ad was fresh and sent a clear message.

Then

Just after this ad Coke's another ad appeared on screens promoting Coca Cola and featuring Imran Khan….

Followed by…..

Pepsi also started showing its new "Ranbir Kapoor" ad on TV, but with the same 'Youngistan' concept ….

But for now Coke wins this ad battle…………..

Similar is the scene with the rising competition - clinical development

versus generic/generic biologics….

The battles seems to be certainly in favor of generics because 3 major trails of 3 major global pharma have been withdrawn in 3 major growing therapeutic areas since the last week as all are aware (Pfizer –Last week, Astra and Roche today.)

http://blogs.veedacr.com/Lists/Posts/Post.aspx?ID=217

Drawbacks of generic Drug substitution- A theory

The need to curb the rising costs of healthcare has led policy makers in many countries to consider generic substitution of various brand name drugs as na effective means to cut costs.

For example, NHS in England began a 3-month consultation to seek views on plans to automatically substitute branded drugs with generic versions in primary care. However, doctors, patients, and advocacy groups—in England and elsewhere—are concerned that generic antiepileptic drugs (AEDs) might not be therapeutically equivalent to branded drugs, which could put patients at risk of breakthrough seizures or other adverse events. Thus, any proposal to implement widespread generic substitution needs careful consideration.

http://blogs.veedacr.com/Lists/Posts/Post.aspx?ID=208

Stopping early can be harmful

Some of the randomized clinical trials if stopped early can lead to misleading results in the late phases according to a recent study in the Journal of the American Medical Association. The Randomized clinical trials provide a fair amount of evidence related to side effects. This can only beneficial if conducted as per the exact protocol guidelines.

The tendency of the investigators is such that they tend to halt the trial once they find an apparently beneficial effect of the drug. Therefore the results may therefore provide misleading estimates of the benefit in the final result.

According to the study authors, to the extent that substantial overestimates of treatment effect are widely disseminated, patients and clinicians will be misled when trying to balance benefits, harms, inconvenience, and cost of a possible health care intervention.

As a conclusion from the study authors:

For trial investigators, the results of the study suggest the desirability of stopping rules demanding large numbers of events. For clinicians, they suggest the necessity of assuming the likelihood of appreciable overestimates of effect in trials stopped early.

http://blogs.veedacr.com/Lists/Posts/Post.aspx?ID=236

Regulations causing decrease in trials in some countries

The CBC is reporting that many clinical trials not happening due to much of the red tape involved when conducting them. This is not only happening in Canada, but all over the world. Many believe that the bureaucratic systems now taking place before clinical trials are getting in the way of finding better ways to help patients.

According to the article, simpler rules are needed to:
* Ensure patient safety.
* Collect information accurately and reliably.
* Provide fair and balanced information to research participants before they consent.

What do you think? Are studies in industrialized nations falling behind because of the new standards? Do the bureaucratic rules help more patients more in the long run?

Read the full article here.

Partnerships in Clinical Trials Latin America Brochure Now Available!

Partnerships in Clinical Trials: Latin America
August 2-4, 2010 – Buenos Aires, Argentina

At last week’s industry-leading US Partnerships in Clinical Trials event, there was lots of buzz about this popular event going to the Latin America region and we look forward to seeing you at this premiere event. With a combination of case study presentations, panel discussions, interactive roundtable discussions, partnering meetings and local site tours, there is something for everyone at Partnerships in Clinical Trials Latin America.

Partnerships is the only event focused on clinical development in the Latin America region with participation from local leadership as well as US-based decision makers including Eli Lilly, Sepracor, Eisai and Millennium: The Takeda Oncology Company and more.

Visit our webpage to find out more and download the brochure!

Reactions to Partnerships in Clinical Trials

With Partnerships in Clinical Trials taking place last week, there were many reactions around the web to the conference and its content. Here are a few:

Partnerships with CROs Wrap-up

Experts share tips for developing drugs using a virtual model

CRO industry poised for recovery--followed by a shakeout

ACRO Funds Global Healthcare Innovation Management Center

Applied Clinical Trials: Partnerships in Clinical Trials

2011 Annual Partnerships in Clinical Trials Event Keynote Speaker and Location Unveiled

NEW YORK & ORLANDO, Fla. -- IIR, the world’s leading knowledge and skills transfer company, announced today the 2011 keynote speaker and location for its 20^th Annual Partnerships in Clinical Trials, the premier conference for clinical outsourcing and development professionals.

The 2011 keynote address will be given by Curt Schilling, former Major League Baseball Pitcher and three-time World Series Champion. He is currently the Founder and Chairman for 38 Studies entertainment company, the Founder of Curt’s Pitch for ALS and in 2010 will make his debut as an ESPN analyst. The 2011 event will be held at the Phoenix Convention Center in Arizona on March 30-April 1.

Lesly Atlas, Director of the Annual Partnerships in Clinical Trials conference, said, “As the pharmaceutical paradigm continues to evolve, sponsors and suppliers must work together now more than ever before to demonstrate value, do more with less, and maintain the highest level of quality and safety. Clinical development teams are driven to find new ideas and partnership opportunities. With the insights gathered by our Advisory Board and intensive market research, our annual three-day annual conference continues to be the top destination for clinical development and outsourcing professionals to address these growing industry issues.”

About Partnership in Clinical Trials

After almost twenty years, the industry and the event have experienced tremendous growth as outsourcing to CROs and other clinical outsourcing providers has become more than a strategy to control costs and expedite clinical trials but literally THE strategy for ensuring value and quality in complex clinical trials. Partnerships in Clinical Trials continues to be the leading global event serving the educational and business needs of pharmaceutical, biotech and medical device executives in the US. To learn more about this event, please visit: www.clinicaltrialpartnerships.com.

About IIR

IIR is the world's leading knowledge and skills transfer company with a global network of 47 companies and 112 operating units. Every year, IIR works with 650,000+ business executives providing them with knowledge and skills through training, conferences, seminars, e-Learning, blended solutions, exhibitions, consulting and mentoring. To learn more about IIR, please visit www.iirusa.com.

Partnerships 2010: Day 3 in Pictures

Day 3 was full of exciting keynote sessions as well as informative tracks. Check out these pictures from Day 3 of Partnerships in Clinical Trials.

Partnerships 2010: New Era of Privacy Concerns for Drug Development: Business Implications for Sponsors and CROs

Moderator: Douglas Peddicord, PhD, Executive Director, ASSOCIATION OF CLINICAL RESEARCH ORGANIZATIONS (ACRO)
Panelists: Carl de Moor, Senior Director, Health Outcomes, PPD, INC.
Eric Gemmen, Senior Director, Medical Affairs, Epidemiology & Outcomes Research, Late Phase & Safety Services, QUINTILES

An overview was provided that addressed the issue of the privacy of one’s health information and the desire for Comparative Research. Central to this debate are the conditions set forth with the HIPAA Guidelines and the American Recovery and Reinvestment Act (known as HIPAA2).

A detailed discussion dealt with the content of what HIPAA covers with respect to the rights that individuals have with their health information and the manner in which human data can be obtained/used for comparative research purposes. Distinctions were made regarding the use of information that can be used versus that which can’t be used and what remuneration would be allowed to obtain such information.

A review of the ARRA 2009 reveals that there is a new emphasis on the protection of health information that is encrypted, which will limit (protect) the use and disclosure of said information. There seems to be a new era of enforcement in the dissemination of this information as there is increased compliance directives as well as increased penalties for violating these directives.

In the event there is unauthorized use of one’s health information, there are certain requirements that need to be met in the reporting of this violation. This involves notifying the individual involved within 60 days in writing and to notify the HHS in the event data from more than 500 people have been affected. The FCC is also involved in the privacy and security issues associated with one’s health information.

Comparative effectiveness research efforts will use certain types of subject information. This would include age, gender, service dates, geography, medical condition, type of therapy, procedures, labs and other demographics. Research networks will also contribute to the collection of this information.

The impact of HIPAA and ARRA on the R&D industry is not fully known. Government information (HHS) was to have been released in February 2010 to address this issue but this release date has been delayed. Only when the government position on these issues is known can a determination be made regarding the extent of the impact on the pharmaceutical and biotech industry.

Partnerships 2010: Growing Traditional Outsourcing Relationships Into Customized Multifaceted Alliances

Panelists:
Mark Harvill, President and Chief Operating Officer, PARAGON BIOMEDICAL
Thomas Engels, Vice President, Clinical Affairs, CARDIOKINETIX INC

This session continued the debate of the full service provider versus the functional service provider. The presentation was an example of how Paragon Biomedical and Cardiokinetix Inc. worked out their business relationship.

The decision process used by these individuals involved assessing the CROs culture/compatibility, the CRO capabilities and finally cost. Key to the selection of the vendor was the recognition that the vendor would be an extension of the sponsor so a “fit” was absolutely essential for the success of this interaction.

The sponsor used a number of metrics by which to assess the vendor. Therapeutic expertise/experience was critical as were the geographical locations the vendor was located in.

They felt that being flexible was a key consideration in selecting the right vendor due to the nature of conducting clinical trials and the many challenges that present themselves.

Some of the other metrics employed in the evaluation of the CRO was cost, CRO assessment of strength/weaknesses, CRO philosophy, governance, human connection, quality, escalation and innovation/evolution. A detailed discussion of each of these metrics was provided.

The presentation was summed up by stating that compatibility and communication were the keys to working together. Emphasis was placed on the social component between the groups that led to the vendor being selected. Constant communication and necessary training was provided on an as needed basis. A shared vision between the groups was also emphasized as being a key factor to success.

Partnerships 2010: Tactical vs Strategic Sourcing: Are the Drivers for Sourcing the Same for Large, Medium and Small Sponsor Companies

Moderator: Andrew Townshend, Senior Director, Contracts & Outsourcing, PFIZER
Panelists: Frances Grote, Senior Director, Strategic Sourcing, MILLENNIUM: THE TAKEDA ONCOLOGY COMPANY
Gary Laine, Director, Clinical Sourcing, Contracts & Payments, ELAN PHARMACEUTICALS
Lauri Sirabella, Vice President, Clinical Strategic Business Development, EXECUPHARM
Mark A. Lanfear, Vice President, Strategic Alliances, KFORCE CLINICAL RESEARCH, INC.

This Q&A session with four panel members covered the debate of whether to use a full service provider versus a functional service provider.

There are a number of factors to consider that will determine which approach a sponsor can or should take. There really was no correct answer as to which provider to retain. A full service provider could offer more flexibility and possibly be more cost effective than a functional provider. However, depending upon whether the approach was tactical versus strategic, one can employ either method or to consider a hybrid approach.

The panel members discussed the processes employed at their respective companies for vendor selection and the reasons for the approach they had taken. Key factors considered when selecting a vendor included business/cultural issues, specific expertise of the CRO, whether the project was a long term program or just a short term assignment, project needs and the relationship that exists between the parties. All panel members agreed that a cohesive and effective relationship was absolutely essential for the success of the project. Adversarial roles can’t be tolerated when selecting a partner. One member stated they focus on the efficiencies and objectives of the job and then to work out the issues contractually.

The question was asked regarding the future of full service versus functional service providers. Again, there is no clear indication of where the industry is headed. The type of provider selected will be dependent upon study specifics, desired locations, expertise needed and the ability of the provider to provide the necessary support to the program. Some companies employed single providers while others used multiple vendors to address the job at hand.

Some companies are outsourcing most everything while others are managing the majority of the project themselves. It was agreed that if the studies were to be conducted in a foreign country, at least the CRA should be a local person while the clinical trial manager may/may not reside in-country.

There did not seem to any correlation regarding the size of the sponsor in relation to the level of support given to them by the CRO. It was stated that the level of attention paid to the sponsor was a function of selecting the right provider in the beginning and had really nothing to do with size.

The success of the partnership is to have and to encourage an open and trusting relationship. The key was to take the time to build this relationship up front as well as over time. Some companies wish to have a stable, dedicated provider by which to move their programs forward. Many use a matrix approach when working with a provider with the expectations clearly defined on the front end. The success of the relationship is related to the people involved and to treat each other as a full partner in the R&D process. Chemistry was also mentioned as a key factor in a successful partnership.

Partnerships 2010: Site Management Contracting: How to Best Define Responsibilities between Sponsors and CROs to Avoid Accountability Disputes

Panelists: Christina DiArcangelo, Associate Director, Clinical Contracts and Outsourcing, FIBROGEN
Lauren Goldsmith, Senior Manager, Strategic Outsourcing, MANNKIND CORPORATION
Eric Strait, Senior Manager, US Site Contracts, Pharma Development Operations, GENENTECH, INC

A number of key elements were discussed when defining the roles and responsibilities of the CRO and the sponsor. The key to this interaction is the upfront work (face to face meetings, kick off meetings) that addresses the specifics of each group’s roles in the development process.

Accountabilities for each partner have to be clearly defined at the outset and if there is a shift in the responsibilities, further meetings are needed.

Sponsors should have a clear fallback position with stated parameters in the Clinical Trial Agreement (CTA). In addition, they should have a concise negotiation plan which stipulates the CRO’s expectations. Mutual expectations are paramount to a good working relationship. The use of CTA templates makes the process much easier should changes need to be made.

CROs should have a clear plan of action that includes how they will complete the project within the agreed upon study timelines.

Both groups will need to be united when dealing with sites so as to not cause any confusion for site staff.

In addition to the defined roles of each party, there should be standard process document that needs to be ratified with the CRO for each study. This document should state clearly which party is responsible for the involved contracts/budgets and that these amounts are final as written. In the event there is a problem/snag on the CRO side, flexibility is needed to respond quickly to the situation.

There should be a clear escalation plan that sets the guidance as to scope of the decision making authority and to know who the decision makers are.

With respect to budgets and payments, there were some Do’s and Don’ts provided.

Do’s

Write down the payment terms

Include expectations for one-off payments
Create payment contact lists for each site
Ensure proper reporting occurs with respect to escrow accounts for investigator payments and to have a 30% trigger
Agree on reconciliation plan
Always know where payments are during the study.

Don’ts

Keep sites in the dark about where and how payments will be generated
Adjust budgets during negotiations
Pay late

Other recommended considerations were:
Have specific metrics in the contract for turnaround times concerning CTA generation/execution
Do include your legal department in the development of a study specific template
Create workflow and escalation paths
Be aware of what was negotiated previously with repeat sites
Do understand the difference between business and legal issues. There have been instances in the past where the CRO has sent business questions to legal and legal questions to business people.

Use Master Service Agreements (MSAs) from sponsors when utilizing academic sites or SMOs. The sponsor will need to communicate to the CRO what sites on the study have a MSA in place so that the CRO can plan accordingly.

There was discussion concerning payment triggers and the managing of the payment expectations. The details of the arrangement should be clearly outlined in writing that include all payment terms. Escrow accounts should have a 30% draw down trigger, account reconciliation should occur during the study rather than at the end of the study, milestone payments should be clearly defined based upon agreed performance standards and to use a CTMS system where possible.

Partrnerships 2010: Thinking Small in Big Pharma: What Will Future Pharma R&D Look Like

Thomas Senderovitz MD, FCP, Senior Vice President, Global Clinical Development, GRUNENTHAL GmbH

The way in which we have been conducting our R&D activities and the manner in which these activities translates into the general well being of our society does not seem to be working very well. This is evidenced by the fact that up to 40% of people receiving medications don’t benefit from them, 106,000 people die a year and there are 2.2 million non-fatal events each year.

Our current model is that one size fits all and that medications are not differentiated. The fact of the matter is that patients are different and efforts should be undertaken to address this diversity in our R&D model. R&D costs with the present system are rising exponentially and the return of share holder value has dropped from 20.3% (1985 – 2000) to -0.7% (2001 – 2007).

Recent estimates indicate that it now takes 13 years and 1.3 billion Euros to develop a drug. The impact of mergers and acquisitions in the development of New Molecular Entities (NME) output is not working as well. Quite frankly, we are at the end of the blockbuster era which was prevalent for many years. The seeking of block buster drugs is no longer a viable business model in today’s times given the previous statements.

The presenter felt very strongly that we have to change our discovery process that will lead to an improvement in the development process resulting in decreased cycle times. Specific steps to take to address this situation were identified as:

• Stratifying personal treatments to individuals needs matching genetic and life style background

• Moving away from one size fits all business model

• Moving away from damaged organs approach to a network based discovery approach

There are multiple areas in the network that will need to be addressed and include:

• Single target drugs versus multiple drugs

• Challenge for regulatory agencies
• Increased attrition rates

It was felt that current disease definitions will disappear. Molecular diagnostics will be employed to address unmet molecular needs and will do so due to earlier intervention and restoration of damaged networks. This translates into early intervention equaling longer treatment.

By using a targeted subpopulations approach, higher efficacy and better safety will be achieved that results in better risk/benefit ratio. All of this leads to a higher compliance in taking of prescribed medications that ultimately result in added value to the customer.

The oveall recommendation was to move from the blockbuster approach towards a stratified R&D approach. This will lead to personalized medicine that will address the uniqueness of each individual.

Modeling and Simulation are a must in the new model of drug development. This will require:

1. Understanding biological networks

2. Translating in vitro and animal data - integrative and translational M&S
3. Designing optimal clinical programs

Building large computer models is needed to simulate human physiology which will lead to the creation of a virtual patient. Other requirements needed to move to the new R&D model include integrated data platforms and real time access to nonclinical and clinical data.

Presently, there are next generation diagnostics (portable data capture devices), next generation sensors (online monitoring of systems on a personal basis, use of I Phone to monitor systems) and next generation drug delivery systems.

An integrated healthcare solution will involve moving from single targets to multiple targets – targeting treatments for intervention, monitoring on-line real time data, early warning using biomarkers before drug interaction is required, using wireless health monitoring devices, personalized treatments and real time biomarker monitoring.

The future of the pharma Industry will include personalized targets for medicine, linking up with diagnostic tools and sensors, increased health surveillance, earlier intervention, using social media and in silico R&D (based on modeling data).

One question that presents itself is how to change the R&D business model in light of current regulatory industry standards. We as an industry need to be bold and to challenge existing methodology. Industry has to make a move to understand the data and make a case for change that will involve the sharing clinical data.

Partnerships 2010: What Does the Future Hold for Sponsor-Clinical Service Provider Relationships?

Moderator:
Patricia Leuchten, President and CEO, The Avoca Group, Inc.

Panelists:
Elspeth Carnan, PhD, Executive Director, Head Global Clinical Site Management, Global Development Operations, Amgen
Mitchell Katz, PhD, Vice President, Global Clinical Development, Eisai Pharmaceuticals
Denise Calaprice-Witty, PhD, Executive Director, Survey Research & Relationship Management Programs, The Avoca Group

The Avoca group shares data and key findings from their annual survey and uses that data as a catalyst for the panel discussion titled above. The focus of this years survey and the question posed to respondents is “ How has outsourcing strategy changed over the last 5 years?” Both Sponsors and CROs were polled and the data correlated to find synergies and separations in expectations in out-sourcing relationships. The full report can be obtained from the Avoca Group, Inc.

The web based survey had 285 respondents split with about a third of the responses from sponsor companies and two-thirds from service providers.

One major finding was that sponsors have consistently reduced their outsourcing to fewer numbers of providers and focus on relationship management. Basically preferred provider relationships. CRO data supported this with CROs focused on building key relationships with Master Service Agreements.

On the part of sponsors the expectations included reduced pricing and focused oversight. No surprise, right? Formal relationship management programs are reported as becoming more prevalent and apparently productive within both the sponsor and the CRO organizations.

Outsourcing spend in real dollars is mostly going to preferred providers and this trend in on the increase. The effect has been that most sponsors are seeing increased satisfaction with the services providers and the value of those services when preferred provider relationships are maintained. Most CROs will not be surprised by this data. It has long been maintained in the service industry that a long-term relationship with a sponsor allows each party to become more aligned with the processes and procedures, and not the least communications expectations of the other and mitigates for more efficiency and quality in the product. CROs looking to break into a new sponsor will be less thrilled with this report.

Large numbers of sponsors appear to be in the midst of launching initiatives internally to systematically manage service provider interactions and in general are increasing investment in relationship management.

The panel reports the use of benchmarking their providers not only on costs but also on value. CROs have their expertise and so do the sponsors. Dr Katz believes in letting the CRO do what the CRO does best. “We need to understand what the CRO has that the sponsor doesn’t and what the sponsor has that the CRO doesn’t and we need to learn to work those synergies together.” It’s worth the investment because in the end you get a better partner. The data seems to say the same.

However, does that thinking, that seems prevalent across this survey, hold true in the face of an economy that provides the opportunity for the sponsor to realize significant savings by shopping for a better value in services? Will sponsors keep shopping at the brand name stores or is it becoming irresistible to have a look at the discounters? CROs report significant price sensitivity and increased expectations. Apparently they are providing those.

What about risk.? Sponsors are looking more and more to mitigate risk and, in some cases, are more willing to share rewards for successful development. What is the CRO/Sponsor relationship when it comes to sharing risks? The issues involve recognition of core competencies internally as well as agreement on the traditional timelines and deliverables. How much of this is actually being implemented. That is less clear.

It would be interesting to look back in 2011 to see how much of this survey has proven to be accurate for forecasting. See you at Partnerships 2011??

Partnerships 2010: Value Creation through Strategic Sourcing and New Business Models

Keynote Speaker:
Jason Hwang, MD, MBA, Executive Director of Healthcare, Innosight Institute; Co-author The Innovator’s Prescription: A Disruptive Solution for Health Care

This is a discussion on using what he calls disruptive innovation to re-invent the pharmaceutical industry. What does he mean? He describes in the terms of centralization or decentralized. Computing for instance began as decentralized with the slide rule where we all carried the solution in our pocket. Then with the advent of the mainframe we had to go to the corporate mainframe to compute. Beginning with the mini computer decentralization began in waves and follows through the personal computer, the laptop, and now handhelds. You get the idea.

This is enabled by disruptive innovation. Essentially as the product, computers, offer more complex innovations users are parsed into those who need those innovations and those who don’t. Basically a spectrum of users needs. Computer producers then can become more diverse with ‘ disruptive’ products that are cheaper, faster, etc, but offer a specific subset of innovations. In other words you can use TurboTax if your tax return is relatively simple but if not you still need an accountant.

Dr Hwang notes that it is usually a new entity that ‘disrupts’ and not a leading incumbent. Mainframe makers are always trying to make the next generation of mainframes. There are exceptions. IBM has been able to sustain business though successive waves of disruption at least to a point.

Simplifying technologies that introduce predictability and obviate costly trial and error experimentation enables disruption. Now it’s beginning to sound like it could apply to health care, right? Dr Hwang puts it n terms of the practice of medicine moving from intuitive to empirical and to precision (redefining categories of disease). Enabling technologies include molecular diagnostics. These types of technologies enable new business models that can alter the landscape of an industry. Think of the IBM Mainframe and Microsoft Windows versus the Dell PC and Linux. With heart diseases you may need the ‘hospital version of the mainframe’. If you have a sore throat you may need a nurse practitioner or self-management.

Pharmaceuticals have traditionally been highly integrated. R&D to Clinical Trials, volume manufacturing, and marketing and sales. The mismatch has been that commercial operations demand predictability from an unpredictable supply chain of drug discovery and development. Remember when computer manufactures used to manufacture and build the units they sold. What happened? It became cheaper and more efficient for come components to be outsourced to multiple vendors. Iteration after iteration until the computer manufacturer didn’t manufacture any part, just marketed the product. Dr Hwang’s contention is that this can and is happening to the pharma industry.

What about generics? Dr Hwang says that they are low-end disruptions using the same business model and that greater impact will come from disruptions that target new markets.

The future will be different than the past. Who will the players be? Basically, those that can piece together the appropriate components. There are several examples. Novartis for instance has announced a companion diagnostic test to screen out patients susceptible to liver toxicity from a Cox-2 inhibitor. Eli Lilly has a division called Chorus focusing successfully on early stage development using a nontraditional lean approach.

Barbarians at the gate? Not necessarily. Surviving disruptive change requires the fostering of riding the successive waves of disruption. Surfing anyone?

Partnerships 2010: The Arranged Marriage: Living with an Outsourcing Partner You Had No Role in Choosing

Panelists: Lynn McGovern, Director, Strategic Sourcing, MILLENNIUM: THE TAKEDA ONCOLOGY COMPANY
Pamela Wohlberg, Clinical Head, Development Strategic Sourcing, NOVARTIS PHARMACEUTICALS CORPORATION
Michael Cox, Manager, Resource Performance Management, MEDIMMUNE

Sometimes you just have to make it work despite initial misgivings. This was the message of the discussion by three sourcing representatives of big pharma companies. Lynn McGowan of Millennium, Pamela Wohlberg and Michael Cox of Medimmune talked about how their companies inherited partnerships through mergers, licensing agreements and co-development.

When Takeda acquired Millennium, the latter inherited new molecules and active projects, including the CROs. Due to differences in how each company did business before the acquisition, there were some initial disconnects. For example, Takeda was used to keeping project management in-house, while Millennium typically outsourced. Different data management systems (Rave vs. Inform) caused some confusion as well. The results of these disconnects were missed deadlines, data issues and a lack of understanding of the larger picture.

To begin to mitigate some of the issues, Millennium and their CRO invested in and committed to successful resolution and got high level people involved, brought in project management resources and re-established joint expectations. Lessons learned: treat a new relationship as a new project and an inherited partner as an intended partner.

When Novartis acquired Chiron in 2006, Chiron had several CRO providers including one large service agreement for global services on a large trial. Novartis inherited a negative scenario where relationships were strained. Challenges included a lack of clarity and specificity in the partner agreement about roles and deliverables. Communication had broken down between parties.

Novartis tackled the issues by setting up a two-day kickoff meeting, establishing new expectations and a full review of assumptions, budget and progress and plans to date. The outcome was a set of amendments to the contract to capture new expectations. All of this contributed to an improvement in the relationship and positive outcomes to the active projects.

MedImmune’s experience with an inherited CRO came via a licensing agreement. In this scenario all companies still have active relationships among all parties which can quickly become complicated and grow the web of contacts exponentially. CROs tend to be caught in the middle, as one sponsor’s processes or audit activities hold up the other sponsor.

Despite the challenges of these “arranged marriages,” positive outcomes can be achieved primarily through rebooting the relationship and giving the proper attention and care to learning about the new mutual partners.

Partnerships 2010: Collaboration in Pharma: Is M&A (and Co-Development Deals) the New R&D

Panelists:

David Reasner, Phd, Senior Vice President, Biostatistics, Data Management, and Health Outcomes, Sepracor

Adrian McKemy, PhD, Managing Director and Practice Leader, Development and Commercialization, Quintiles Global Consulting

It’s all about risk! Everyone feels that there is too much. Everyone is looking to hedge against it. Hence the call to co-develop with either a corporate of a venture capital partner.

Deals are more of a dialog today. This notion is supported by the dramatic increase of ‘options’ based deals with specific milestones as opposed to the ‘whole hog’ deals more prevalent in 1980’s and 90’s. After all, no one likes to make long-term decisions with little information. In doing so one can wind up with a ‘permanent reminder of a temporary feeling’.

This leads to a discussion of governance and governance committees (GCs). Dr Reasner defines governance as a script without a dialogue in which one individual may play many roles and this particularly within small companies. He points out that the governance structure is really to manage the contract and may not be particularly helpful in managing the company to value. Interdependence is a key consideration in developing a governance committee and appropriate metrics need to be in place to measure whether the desired outcomes are being approached. Dr Reasner likes to structure a GC with co-chairs in order to get at least one relationship “up and running”.

Organizational costs should be considered. Interdependence requires maintenance. What else could your executive team be doing with that time? Are they already doing too much to execute well in an interdependent governance committee. Basically what he is talking about is ‘opportunity cost’. Do your really want that much time taken out of your executive team?

Usually there is one key person that is talented in communicating the value and culture aspects to be considered and this person can be extremely valuable to success. This person is not always a senior member. Don’t lose the opportunity to fully utilize this resource. This is the alliance manager either in fact or de facto.

What is the objective of the partnership? It’s important not to lose sight of the goal. “Eyes on the prize.” Ultimately, when the inevitable difficulties arise, do you want to ‘be right’? or do you want to succeed?

Partnerships 2010 Live: Are There Really Strategic Site Partnerships?

Panelists:
Kenneth Getz, MBA, Senior Research Fellow, TUFTS CENTER FOR THE STUDY OF DRUG DEVELOPMENT
Christine Pierre, President & CEO, RXTRIALS INSTITUTE

Kenneth Getz kicks off the panel by discussing the overall market conditions. Market conditions are really the perfect storm. There is a high level of uncertainty going forward. There is a dramatic shift in management of operating costs and he covers some commercialization and R&D operating conditions.

Commercialization Conditions
- Restrictive price controls
- Healthcare reform uncertainty
- Depressed global markets
- Intense competition

R&D Operating Conditions
- Low success rate
- Declining levels of innovation
- Rising R&D costs
- Competition
- Staff consolidation
- Public discontent

Some benefits are:
- Improved protocol design feasibility
- Faster study start-up
- Higher level of process integration
- Improved quality of study results

Some Risks are:
- High financial risk exposure
- More concentrated operating risks

Christine Pierre starts off her talk with an analogy about getting the ultimate experience when buying shoes at Nordstroms as compared to a lower cost store like PayLess. At Nordstroms, she gets higher quality and a better quality experience because Nordstroms goes beyond just taking monies by documenting and referencing the customers’ needs and wants.

Sites the silent partner:
- Unsustainable model
- Only 1 out of 12 products approved
- Prioritize your spend
- Measure metrics
- Seek long term relationships
- High Value Partnership ActivitiesProfessionalism
- Project management
- Operations
- Payment process

" Why aren’t we creating partnerships with volunteers? A good question! "

Key take-away: Ultimately, you need to build good and quality relationships to make partnerships work. This is an on-going need to have strong partners. Again, we hear about the need for finding the right collaboration partners – ones that are knowledgeable and know all aspects of the various business goals/models.

Key take-away: Do not reinvent the wheel for every situation instead manage for success by establishing sponsor-site alliances!

Partnerships 2010: Keep the Spark Alive: Evolution of the Business Relationship

Panelists:
Jennifer Charron, Associate Director, Clinical Programs, RPS, INC
Susan Torchio, RN, BSN, Associate Director, Clinical Operations Resourcing & Pain, CEPHALON, INC

Jennifer Charron of RPS, Inc. and Susan Torchio of Cephalon, Inc. presented on how their companies developed a working partnership. Ms. Torchio started by describing how the workforce was consolidated to create a single pool of CRAs and CTMs and employees of Cephalon were offered the choice of moving to RPS during this process. She went on to talk about the key performance indicators, relationship management and new policies that would be shared between the companies.

In the first year of the partnership, there were struggles in the merging of processes and a lack of buy-in from employees. Ms. Charron told us how RPS responded by holding national meetings, monthly calls, conducting surveys and increasing email communication to outline goals and rationales. Feedback was not always positive but was helpful in discovering the gaps in the process and what was needed to form a cohesive team. Lessons learned included the importance of having all parties contribute to the process and involve key stakeholders in the approval process so that when it rolls out, all are in agreement.

Some tools that were used in the evolution of the relationship were a governance committee, an executive committee, KPIs, a relationship management plan, new policies and procedures and a quality management plan. The last item included CVs, job descriptions, org charts, SOP processes, IT systems and a detailed training plan.

Today, the companies continue to re-evaluate their relationship and update the management plan annually. Through open and collaborative communications, the evaluation of goals and continual assessment of quality, the companies are able to keep the relationship fresh and viable.

Partnerships 2010: Let’s Make a Deal: Breaking Out of Organizational Silos – Bridging the Gap from Clinical Development to Commercialization

Moderator:
John Doyle, DrPH, SVP, Quintiles Consulting

Panelists:
Deirdre BeVard, Vice President, Clinical Operations and Data Management, Endo Pharmaceuticals
Alan Butcher, Vice President Business Development, Endo Pharmaceuticals
Peter DiBiaso, Senior Director, Clinical Planning and Performance, Vertex Pharmaceuticals
Karen Gallagher, Director, Clinical Programs and Due Diligence, Shire Pharmaceuticals

The topic is the convergence of clinical and commercialization. The panelists come from backgrounds that emphasize partnering as a way to mitigate capacity or capability constraints, clinical operations, and new compound and acquisition assessment that would seem well suited to addressing the topic.

The integration of clinical and commercial strategy is not a new goal. The roots of the modern iteration can be traced back to the 1980’s when the ‘hand-off’ or ‘throw-the-baby-over-the-wall’ method from clinical to commercial was deemed insufficient in terms of more, better, and faster. Bridging those silos mitigates risk by supporting enhanced due diligence both within an organizations infrastructure and, in the case of corporate partnerships, acquisitions or mergers, externally.

The empirical evidence of clinical efficacy has become the buy-in. The accurate valuation of the product over the entire lifecycle is necessary to produce the high value product desired. Health economics must be considered early in the process and continually reassessed throughout the development and marketing process.

Especially in today’s uncertain healthcare environment a collaborative approach is necessary so that the data and information collected all along the R&D continuum is ‘captured’ for data mining and decision-making throughout the organization and not ‘captive’ within any one part or division of the organization.

This supports the currently refocused interest in predicting what ‘comparative outcomes research’ will be performed, comparing what products, and how will this affect the product portfolio decisions internally and early on in the decision-making process. Anticipated comparator studies are, or should be, becoming more ‘baked in’ to the clinical development plan early in the process. Since there is not unlimited resource for performing ‘dueling’ comparisons in attempts to regain market share, initial studies can be shaped to address potential downstream comparator studies.

How does this play out in evaluating a pre-market product and/or a post-market product with regards to partnering or acquisition or even de-novo development? Clearly the take home for a biotech wanting to work a partnership with their product is that the products value is enhanced if R&D is encouraged to develop this ‘commercial’ mindset.

The summary here is all around the mitigation of uncertainty to increase confidence in valuation. In this uncertain climate with health care payer reform, insurance reform, and health care delivery reform the message from Senator Daschle, uncertainty is not likely to be calmed quickly.

Partnerships 2010: The Otsuka-Covance Collaboration: A One Year Report Card

Moderator: David Zuckerman, President, CUSTOMIZED IMPROVEMENT STRATEGIES, LLC
Panelists: William Carson, MD, Senior Vice President, Global Clinical Development, OTSUKA PHARMACEUTICAL DEVELOPMENT & COMMERCIALIZATION, INC
Richard Cimino, President, Clinical Development, COVANCE, INC

In 2009, Otsuka Pharmaceuticals, after a thorough CRO selection process, established a strategic partnership with Covance. The intention of the partnership was to move beyond a traditional tactical vendor/sponsor relationship and become a true collaboration of partners. David Zuckerman of Customized Improvement Strategies moderated a discussion between Rick Cimino of Covance and William Carson of Otsuka, about how the collaboration is working after its first year.

Mr. Zuckerman started with a brief introduction of why Otsuka chose to strategically outsource. First of all, they needed cleaner data and faster time to market. Also, with a larger pool of people there are more opportunities to develop drugs and there is broader expertise and increased flexibility.

Otsuka selected Covance based on cultural fit and a collaboration based on vision and strategy. The change was managed by both companies but they chose to have a third party facilitate the partnership. The transition of work from tactical providers to Covance took place gradually over time. Relationship managers were put in place at key points. Goals were seamless integration, and good, clean auditable data.

So how did it go? In 2009, multiple projects were started, cycle times reduced, processes were harmonized and integrated and best practices developed. Joint pipeline planning was also initiated and governance was integrated. For the future, in 2010 the goal is to be a breakthrough year and 2011 will be to extend and consolidate.

Mr. Cimino and Mr. Carson discussed what was attractive to each company about the other. Core values that were shared between companies were a major factor in the compatibility. Mr. Carson said that in the selection process, several of the CROs in the running did not take the RFI seriously and did not tailor responses to the specific scenario. Mr. Cimino said that while Otsuka was screening partner CROs, Covance also had to determine whether the fit was right for them.

Both men talked about how this collaboration differed from others their companies have had in the past. One major difference cited by Mr. Cimino was the speed with which the relationship took off and the extent to which knowledge was shared between the companies. Mr. Carson talked about the change within Otsuka, a traditionally conservative, private company, and how early the company was willing to get Covance involved in the discovery period of drug development.

Mr. Cimino finished by discussing the lessons learned and key goals for the collaboration in the near future.

Partnerships in Clinical Trials APAC coming back this October!

This October 6-7, 2010, we look forward to the 2nd Annual Partnerships in Clinical Trials Asia Pacific Event series in Singapore.

With the success of the Partnerships in Clinical Trials APAC launch In December 2009, this invaluable opportunity is coming to the Asian-Pacific market for the second year running. From understanding the operational advantages of regional CROs to regulatory nuances, Partnerships in Clinical Trials offers specific insight into what types of relationships are working in Asian-Pacific markets with case studies and best practices in regions including Japan, Korea and the Philippines in addition to China, India and Singapore. Participating in Partnerships in Clinical Trials enables you to master the unique operational, regulatory and ethical challenges in each market.

Last year, the Partnerships blog team was on site to capture much of the event live. Click here to see the footage.

Why the Future of Business is Selling Less of More: Has the Long Tail Phenomenon Caught Up with Big Pharma?

Chris Anderson, Editor-in-Chief, Wired Magazine and Bestselling Author, The Long Tail: The Future of Business is Selling Less of More and Free: The Future of a Radical Price

Chris Anderson discusses technology and the transformation of clinical research in terms of the explosion of and access to relevant data. He calls this the ‘golden age of data acquisition’. He compares our industry in some respects to the music industry. Music appreciation is at an all time high. Ipods, etc rule the day. Accessing music online is the major source. The only area of the music industry in decline these days is the music label’s sale of hit albums or “blockbusters”. Sound familiar? His point is that this is not a crisis in music appreciation but a fragmentation of market share. He quips, “We are not a mass market, we are mass niches”. And technology has created both a near-zero cost to distribution and an explosion of content available. While everyone is enjoying ‘music’ there are hundreds of niches so as the number of products increase it creates a ‘long tail’ where popularity of a specific product declines in favor of personal selection amongst more and more products. And today there is ‘unlimited shelf space’ for products. This makes identifying peoples unique needs critical.

Does the same apply to the drug industry? Seventy five percent of the audience thinks so. So does Mr Anderson. What are the drivers? No mystery. These are things we have been talking about for some time.

Moving from Blockbusters to Nichebusters

Diagnostics boom leading individualized patients

Electronic medical records allow better targeting

Informed and empowered patients demanding more specialized care

In essence - One size fits all to personalized medicine

In effect personalized medicine is the long tail. Difficulty of execution in the construct of the industry? Extreme

When will it arrive? Most of the audience is thinking at least 5 to 10 years although a few percent say ‘never’. Mr Anderson thinks that maybe we just don’t understand what personalized medicine will look like. We tend to think of it in terms of institutions. Mr Anderson sees it in terms of personal best interests and technology, in this example ‘sensors’, mitigating for our creating personal positive feedback loops. In fact, aiding negative behavior modification. Personal sleep monitors are pocket sized and can record more data than a sleep lab, over a much longer period of time and at a much lower cost. One can use the data personally correlating it with weight, consumption, etc to create a personal set of observations in daily living. We don’t think of this as a clinical trial but Mr Anderson claims the impact is similar. He is right that we are all constantly gathering data and making decisions.

But will we be willing to share this data? It’s fine for data, especially personal physical or medical data to be captive within for personal health or lifestyle decisions. And we can already see some of this happening. Personal blood sugar monitors are an easy example. But are thousands of people willing to put that data online? And are they willing to share along with that their lifestyle, consumption and medication history. Can these data be captured for more public or industry use? I don’t know. Maybe?? Clearly though the current drug development and regulatory structure would need to be transformed dramatically. Is the new healthcare legislation a driver in favor of that?

And -Who are the victors? Mr Anderson thinks that the winner, like in the music industry transformation, will be the consumer.

Partnerships 2010: Chairperson’s Welcome and Introduction of Day Two

Jack Dean, Ph.D., Sc.D. (Hon.), DABT, Fellow ATS, President, DRUG DEVELOPMENT ADVISORS, LLC; Professor, Colleges of Pharmacy & Medicine, University of Arizona; President US R&D, Sanofi-Aventis (Retired)

After a busy and productive Day One, event chairman Jack Dean welcomed conference attendees back for the final day of the Partnerships conference. Dean presented some highlights from Day One’s different topical session tracks.

In Track A, CRO financial outlook is looking better and there is a move towards more strategic relationships. In Track B, it was agreed that there is a need for auditing for CROs and data should not be relied on alone. In Track C, there was a focus on safety and risk management and the use of REMS, as well as a close look at conducting trials outside the US. Track D looked at early clinical development, specifically looking at biomarkers, the use of eCTDs, and the changes in paradigms in oncology. Track E looked closely at cost management.

Dean then looked ahead to Day Two, with a couple of exciting keynote talks before the session tracks open for the day.

Partnerships 2010: 1st Annual Stand Up & Run Cure for Cancer

Day 3 began with the 1st Annual Stand Up & Run Cure for Cancer hosted by RPS. Many of the Partnerships in Clinical Trials attendees joined us at sunrise to benefit cancer. Here are a few photos from the event and thank you to everyone who came to run for a cure!

Partnerships 2010: Day 2 In Pictures

Many of exciting moments of the 19th Annual Partnerships in Clinical Trials were caught by our camera. View the slide show here:

Partnerships 2010: Where in the World is My Clinical Trial Manager? Managing Virtual Teams Across the Globe

Panelists: Lisa Feeney, Director, Clinical Operations, EXECUPHARM
Jessica Mills, Associate Director, Program Study Manager, PFIZER
Elspeth Carnan, PhD, Executive Director, Head Global Clinical Site Management, Global Development Operations, AMGEN
Diane Lewis, PhD, Director, COVANCE INC

This was another Q&A session that was made up of two members from the sponsor side and two members from the CRO side.

There was consensus that there was a shortage of qualified clinical trial managers (CTM) in emerging markets. To address the CTM issue in these markets, some of the panel members state that they outsource this function to locally available personnel. They also use functional service providers (FSP) in regions where they do not have a physical presence.

CTMs require years of experience to be fully proficient in their duties. This can take years to acquire the needed skills that are approrpiate to handle the assigned tasks. The key to this as explained by one panel member is to develop strong relationships between all team members including the local CRA and CTM. Some CRAs act as in-country/site managers due to their knowledge of existing social, cultural and regulatory matters.

Some comments regarding managing global trials included the use of FSPs for key operational activities as well as to grow internal personnel for these types of positions. Without question, the CRA needs to be a local given the communication issues involved in addition to those previously mentioned.

The makeup of the team is project dependent. Typically, a matrix environment is employed when forming a global team. This approach provides for clarity in assigned roles of the team members.

Problems or challenges faced when conducting studies in an emerging market include communication, time zone differences, lack of cultural understanding, connections issues associated with the internet of teleconferencing and difference in the understanding of terms used from one reegion to the other.

Partnerships 2010: Sourcing to Low Cost Regions: Panacea of Piece of The Puzzle

Sourcing to Low Cost Regions: Panacea or Piece of the Puzzle?
Moderator: Jeffrey Kasher, PhD, Vice President and COO, Global Clinical Development, ELI LILLY & COMPANY
Panelists: Graeme Currie, PhD, Vice President, Clinical Operations, SEPRACOR
Mitchell Katz, PhD, Vice President, Global Clinical Development, EISAI
Elspeth Carnan, PhD, Executive Director, Head Global Clinical Site Management, Global Development Operations, AMGEN
Ginny Payeur, Vice President, Global Sales, PSI

This was a Q&A session where several questions were posed to a panel of four members.

The first question asked was related to the percentage of patients that each member had outsourced to an emerging market. The responses varied from less that 10% up to more than 50%. One member stated that they will continue to outsource as much as possible.

The second question asked was whether cost was the motivating factor for outsourcing to emerging markets. The responses were one yes and 4 no.

The third question asked to the group was what were the top three reasons for doing business in an emerging market. Most all panel members stated speed of development, a decrease in available subjects , reduced costs, regulatory hurdles within varying countries, the in-country practice of medicine, the feasibility of each region given medical practice and qualifications, delivering of study objectives within agreed upon timelines, quality of the data and key opinion leaders (KOL).

The fourth question involved whether a company would conduct studies in a given country even though they had no commercial interest in marketing their products there. The answers were that yes, there are instances where it makes sense o conduct studies in countries where there is no marketing interest.

The fifth question asked was related to which country was the most difficult to conduct studies in. The major markets identified included Russia, Asia Pacific, Eastern Europe and India.

The final question asked was how to deal with differences in medical care in the various emerging markets. The majority of answers included the data collected as a part of the feasibility study and extensive training for all involved parties.

Partnerships in Clinical Trials - Wall Street's 2010 Forecast and Analysis of Outsourcing Trends

Moderator: John Kreger, Equity Research Analyst, WILLIAM BLAIR & COMPANY
Panelists: David H. Windley, CFA, CPA, Managing Director, Healthcare Equity, JEFFERIES & COMPANY
Eric Coldwell, Managing Director, Healthcare Distribution and Services Equity Research, ROBERT W. BAIRD

A panel discussion was held to address Wall Street Observations related to the pharmaceutical and biotechnology industry. Overall, there is optimism that these sectors have seen the worst and the forecast is that the industry will grow slowly over time.

The major factor impacting the industry is the economy over the last 2 years. Numerous indicators were discussed to drive home the fact that the industry is now in a recovery mode. The future, according to panel members, appears to be favorable for pharmaceutical and biotech companies.

Investors have high optimism as there is readily available cash for investment purposes. CRO stock prices are high and have done well in a down economy. Growth was modest at best but it was growth none the less. Gross margins, net profits as well as operating expenses were up across the board for the top six pharmaceutical companies.

Predictions for the future included increased budgets, available money for investment purposes and R&D spending will be increased. It is thought that most companies will look for licensing efficiencies as a future strategy for growth. Larger companies appear to be funneling their resources into fewer, global CROs. It was also stated that R&D growth must be adjusted to lower ROI environment given the state of the economy.

Partnerships 2010: Mitigating Sub-Contractor Risk: How Do You Manage the Pieces of All the Moving Parts

Moderator: David L. Bartholomew, Senior Director, Contracts and Outsourcing, PFIZER
Panelists: Jay Turpen, Advisor, Clinical Project Management, ELI LILLY & COMPANY
Jon Lee, Vice President, Development Operations, CEREXA
Larry Florin, Section Director, US Clinical Outsourcing, ASTRAZENECA

A Q&A session was held that included four panel members who addressed the interaction between sponsors and vendors. The consensus was that there was no single answer in managing the risk involved in this interaction.

All of the panel members qualify their vendors by utilizing their own standardized qualification parameters. Key to managing this interaction is to develop a good working relationship with the vendor that ultimately builds trust between the partners. One panel member suggested working with other vendors to ensure fairness and equity in the vendor selection process.

Some vendors are allowed to sub-contract some of the activities while others are not. These decisions are based upon internal decisions. Regardless of whether the vendor sub-contracts or not, it typically is the responsibility of the clinical project manager to keep abreast of all activities. These are the primary individuals that are responsible for managing of these relationships as well as keeping track of vendor performance.

More primary vendors are being given more operational accountability. This is based upon the relationship that exists as well as the internal staffing that may/may not be available at the sponsor. This means that the vendor is empowered to make key decisions on behalf of the sponsor as long as the sponsor is informed as these events occur.

To ensure success working with vendors, all involved personnel are invited to attend a project kick-off meeting which typically lasts two days. All aspects of the project are discussed in detail that includes accountability and responsibility for the project. The key to working with a vendor is to spend as much time up front with each other to address any and all project related issues. Written documentation of these meetings is essential there is a dispute later in the project.

A number of metrics are employed to measure performance. Again, these are maintained by the clinical project manager and reported to the team members on a frequent basis. A very basic indicator of acceptable performance is whether the vendor receives additional work from the same sponsor. The old adage of past behavior is a good indicator of future behavior applies well to this situation.

The panel members suggested using competitive bidding or preferred vendors for multiple bids. They also encouraged vendors to use specific sub-contractors (women/minority owned companies, veterans etc.) to meet applicable government requirements, when appropriate.

Partnerships 2010: Achieving and Maintaining an Ideal Partnership in Drug Development Outsourcing

William Sharbaugh, Chief Operating Officer, PPD, INC.
Mitchell Katz, PhD, Vice President, Global Clinical Operations, EISAI

This presentation focused on the partnership that has been established and developed between PPD and Eisai Pharmaceutical Company.

Opening comments were that the patent expiration cliff is now. It is incumbent for companies to strengthen their pipeline as soon as possible. It was also noted that there are changes occurring with respect to the relationship between the CRO and sponsor.

The PPD/Eisai relationship has been in existence since 1995. As evidenced by this example, a good strategic relationship takes a long time to develop and with much effort.

Past relationships have been tactical in nature. This means that the previous interactions have been a fee for service, preferred partnership or a price for volume for services provided. The past model is one in which the sponsor gives responsibility/accountability for a function or service to the CRO.

The new model is structured such that value is created for both organizations. It is a matter of the sponsor stating the desired business outcome and the CRO developing the processes to achieve the stated outcome. A good working relationship will take up to 3 – 5 years to build that will result in mutual confidence and respect for both parties. The new strategic Partnership should move from transactional to portfolio partnering and to make the necessary investments to grow and thrive.

Issues associated with selecting the correct CRO include key core competencies, sponsor needs to leverage outsourcing goals, to achieve greater operational efficiencies, higher quality, improved performance and shorter timelines.

Eisai trimmed down their service providers from many down to 2 global providers. The understanding by this arrangement was that each CRO was given one specific area of development and they were treated as equal partners in therapeutic development efforts. The continuation of this working arrangement was based upon the understanding that the contract was the CROs to lose based upon their own efforts/activity (performance) as well as maintaining a clear cut team for all activities leading up to registration.

The selection criteria for this process was based upon therapeutic expertise of the CRO, assessment of Eisai processes by PPD, performance, creative accounting, partnering experience, good presentation, CTMS experience real time, EDC capabilities/experience.

Benefits to Eisai – increase in pipeline throughput, faster drug development programs, reduction in Contract to work Order Time, Access to data in real time, reduction in CRO oversight.

PPD benefits – greater team empowerment, internal job satisfaction, dedicated team sequential to project roll over, increased staff retention, joint process and process improvement, decreased project start up time, decreased investment and guarantee investment stream.

The Eisai short term strategy used to prepare for this dynamic shift required an internal cultural change. The partnership was introduced internally by using presentations, conducting internal surveys, baseline data for blending of services was obtained and held many internal training meetings.

The success of PPD and Eisai working together has created a movement to shared visions and values, higher level of trust, aligned goals and incentives, derived greater values in working together, brought about senior management engagement and could possibly serve as model to industry.

Partnerships 2010: Clinical Trial Requirements: Similarities and Differences from a Global Perspective – Managing and Executing a Trial

Panelists: Graciela Racaro, Senior Director, Global Research Operations, PAREXEL INTERNATIONAL
Jacqueline Mardell, Formerly Senior Director of Clinical Operations, METABOLEX INC
Larry Fiori, Associate Director, Clinical Trial Outsourcing & Compliance, Compliance & Quality Management, BOEHRINGER INGELHEIM PHARMACEUTICALS, INC.

While a shrinking world presents new clinical trial opportunities to sponsor companies, the challenges of conducting trials globally that are approvable by regulators can be daunting. Ever-changing country-specific requirements can slow down trials. Should these different requirements affect country selection for trials? Does a sponsor need an in-country partner to help? How can you manage vendors around the world? A panel of experts addressed these issues Tuesday afternoon.

Graciela Racaro of PAREXEL presented some critical success factors to carrying out global trials:

• Carrying out a feasibility study before country selection
• Developing a study start-up strategy that takes into account country-specific issues
• Learn local regulations and what the critical path is to getting a study approved in a country
• Developing patient recruitment and retention strategies
• Logistical concerns (time zones, language)
• Establishing expectations for monitoring quality
• Development of a risk plan and mitigations

Larry Fiel of Boehringer-Ingelheim encouraged sponsors to dig deeper when a CRO says they can manage trials in other countries. Ask questions about their facilities and staff and experience and capabilities. He also pointed out that regardless of where you’re running a study, there are three areas a sponsor must pay attention to: data integrity, patient safety and regulatory compliance. Mr. Fiel also gave some further ideas:

• Plan ahead
• Appropriate and documented qualification assessment of vendors and CROs
• Use of Quality Agreements
• Build site and trial escalation processes upfront
• Conduct interim lessons learned meetings
• Coordinate for global inspection readiness
• Have an experienced trialist in each country and consider using a regional supervisor

Jacqueline Mardell presented some case studies demonstrating some of the challenges in global clinical trials. For example, in February in Russia, there was a halt to all clinical trials due to the absence of one official in the government who could sign off on approvals. Needless to say, this caused confusion and problems for sponsors and CROs alike. In another example, the patient data collection in a developing country ground to a halt due to a lack of infrastructure or mechanisms to track PROs from a largely illiterate patient population.

The key takeaways from this discussion really centered on planning ahead, utilizing local resources and experienced partners and doing homework on country-specific regulations.

Partnerships 2010: What Venture Capitalists and CEOs Look for in Early Drug Development Plans

Panelists:
Elizabeth Stoner, Managing Director, MPM Capital
Dr. Gary Shangold, CEO, Xanodyne

Venture capitalists willing to brave the turbid waters of the pharmaceuticals industry are becoming a bit rare these days. For those that do there are significant risks and sometimes-good rewards. Ms Stoner reports that the state of the industry is that capital investment in the industry is declining with current levels of $$ investment at a 5 year low. A significant number of biotechs have collapsed from lack of funding as later stage deals become more prevalent. “Capital efficiency” is the buzzword in the Venture Capitalists world. Ms Stoner believes that we haven’t yet seen what the most recent round of mergers and acquisition means. Effectively there are 20% fewer pharma companies meaning that the pools of customers for CROs are down to 80% of previous levels. Investors today are looking for a single round of financing to exit these days. In addition, the size of the initial investment is down. “Capital Efficiency” indeed.

In the face of this Biotech companies need to be ‘leaner’. Why? The real value of the company today doesn’t occur until Proof of Concept. In 2009 there were no pre-clinical deals and only one Phase I deal. The big deals are in Phase III. Companies must survive and get to the successful Phase II with the least amount of money and the shortest timeline. It seems that VCs are also risk averse. Incremental value is not good enough to warrant investment. Biotechs must focus on addressing unmet medical need. Not too different from ‘Big Pharma’.

Where do CROs fit? There is significant price sensitivity, no news there, but biotechs are still looking for the experience to achieve cash-efficient drug development and a clear path to proof-of-concept. Not just the result of a Phase II but a clear vision of where the putative product fit in the marketplace.

Dr. Shangold discusses the small company CEO perspective and perspectives of a number of CEO’s who he interviewed in preparation for this discussion. Confirming and expanding on Ms Stoner’s data he reviews the sharp decline in funding over the past few years and particularly since the recognition of the global recession in 2008. In his view creating a new, vertically integrated company is nearly impossible today. Acquisition is practically the only path, still not easy because for one reason the marketplace of buyers is extremely heterogeneous.

Increased time and cost required for R&D, is compounded by increase attrition rate for new drugs. Imperatives driven by this include are ‘lean management’ and early termination of losers, focus on proof of concept and activities that reduce risk on the way to POC. Dr Shangold walks us through specific activities that mitigate in favor of success.

In the end - “ The company’s strategic vision needs to be clear and the decisions around what drugs to develop informed by that strategy.” Is 'speed to market' or 'maximizing commercial return' most important? The answer is Yes.



Venture capitalists willing to brave the turbid waters of the pharmaceuticals industry are becoming a bit rare these days. For those that do there are significant risks and sometimes-good rewards. Ms Stoner reports that the state of the industry is that capital investment in the industry is declining with current levels of $$ investment at a 5 year low. A significant number of biotechs have collapsed from lack of funding as later stage deals become more prevalent. “Capital efficiency” is the buzzword in the Venture Capitalists world. Ms Stoner believes that we haven’t yet seen what the most recent round of mergers and acquisition means. Effectively there are 20% fewer pharma companies meaning that the pools of customers for CROs are down to 80% of previous levels. Investors today are looking for a single round of financing to exit these days. In addition, the size of the initial investment is down. “Capital Efficiency” indeed.

In the face of this Biotech companies need to be ‘leaner’. Why? The real value of the company today doesn’t occur until Proof of Concept. In 2009 there were no pre-clinical deals and only one Phase I deal. The big deals are in Phase III. Companies must survive and get to the successful Phase II with the least amount of money and the shortest timeline. It seems that VCs are also risk averse. Incremental value is not good enough to warrant investment. Biotechs must focus on addressing unmet medical need. Not too different from ‘Big Pharma’.

Where do CROs fit? There is significant price sensitivity, no news there, but biotechs are still looking for the experience to achieve cash-efficient drug development and a clear path to proof-of-concept. Not just the result of a Phase II but a clear vision of where the putative product fit in the marketplace.

Dr. Shangold discusses the small company CEO perspective and perspectives of a number of CEO’s who he interviewed in preparation for this discussion. Confirming and expanding on Ms Stoner’s data he reviews the sharp decline in funding over the past few years and particularly since the recognition of the global recession in 2008. In his view creating a new, vertically integrated company is nearly impossible today. Acquisition is practically the only path, still not easy because for one reason the marketplace of buyers is extremely heterogeneous.

Increased time and cost required for R&D, is compounded by increase attrition rate for new drugs. Imperatives driven by this include are ‘lean management’ and early termination of losers, focus on proof of concept and activities that reduce risk on the way to POC. Dr Shangold walks us through specific activities that mitigate in favor of success.

In the end - “ The company’s strategic vision needs to be clear and the decisions around what drugs to develop informed by that strategy.” Is 'speed to market' or 'maximizing commercial return' most important? The answer is Yes.

Partnerships 2010: Meeting Global Regulatory Requirements in Early Phase Studies

Panelists:
Dr. Bengt Danielsson, Vice President, Pharmanet Consulting
Dr. Andrew Chang, Executive Director, Pharmanet Consulting

Dr Danielsson discusses new regulatory guidance for exploratory clinical trials addressing entering human trials as early as possible in what has been called the Learn-Confirm Model of drug development. What practical tools facilitate this new model? Dr Danielsson cites both early assessment of toxicity (TQT type trials for instance) and identification of efficacy (Proof of Concept). Dr Danielsson reviews the new ICH M3 Guidance focusing on microdosing either in single of multiple dose designs as tools that can mitigate for successful outcomes in these assessment He summarizes that Exploratory Trials utilizing these tools are becoming more commonly accepted in the UK and reports that trials using women of child bearing potential or pediatrics may require more data collected in these exploratory trials prior to more traditional SAD/MAD studies.

Dr Chang discusses globalization of clinical trials and presents an overview of regulation in China. Her reports the steady increase of trial in the EU and Asia corresponds to a decrease of trials solely run in the US. What are the drivers? Time and money as well as the emerging market for medical care in both China and India.

Dr Chang reports that tier one market, Singapore, Hong Kong, Korea, and Taiwan all have very mature clinical trial structures. Tier two, China, Malaysia, Thailand, Philippines, and India have a fast pace of change but represent areas of significant interest for pharmaceutical development players mostly due to access to patient populations even in the face of longer approval times now seen there.

Following on - Dr Chang details the differences and similarities in these countries with regards to First in Man studies contrasting US guidance and pointing out the significant differences. He goes on to discuss and regulatory timeline constraints in these emerging markets and details specifically the Clinical Trial Application and IND review processes specifically for China.

There are new changes in China’s regulations for 2009 designed to increase awareness of the need for innovation and Dr Chang reviews these in detail.

Looking to do business in China? Dr Chang believes the question is not whether to do it but ‘when’ and ‘how’.