In Frost & Sullivan's latest U.S. CRO Market report, it noted that the overall U.S. CRO market had revenues of $9.77 billion in 2008, with projected 2015 revenues at $23.78 billion. Where were the growth spots for the CROs? One large area is early stage work. 

Barath Shankar, author of the report, told 

 that the trends indicate that big pharma is outsourcing the start-up, early phase work of clinical trials to the CROs. This frees up the sponsor to work on pipeline development through mergers, acquisitions or in-licensing. 

This observation has already come to fruition with the big three mergers of first quarter 2009: Roche/Genentech, Pfizer/Wyeth, and Merck/Schering-Plough. However, its effect on the clinical trials industry still remains to be seen. 

As far as compound licensing trends, a 2007 Tufts CSDD analysis showed that in 2005, 44% of New Molecular Entity (NME) approvals came from large pharma, while 56% came from small/mid-tier pharma. However, new drug approvals from 2000-2006 indicate that the origins of approval were 66% for large pharma, and 28% for small/mid-tier pharma. 

In the Frost & Sullivan report, Shankar noted that some areas of outsourced early-stage work, primarily toxicology, are historically underpenetrated. The top 10 CROs account for 55% to 60% of the global market, and most, according to Shankar, already have an early stage capability. Many are increasing their breadth instead of depth, which is achieved through capital expenditures (building it in-house) or acquisitions. 

"Even in terms of adding capabilities, acquisitions may not be happening soon," said Shankar. "There still could be a lot of consolidation among the third-tier, and Mom and Pop shops. However, we'll know more when the funding situation eases a bit." 

Shankar concluded with the following economic observation: "Our estimates are a bit more conservative now. A lot of these projections were done before the market meltdown [the report was released in October 2008], so the numbers could be less." 

The economy notwithstanding, many CROs have been making early phase service announcements. The Frost & Sullivan report specifically noted: "There is a strong demand for early stage services from the supply side (R&D spending) that could translate to higher business for CROs if their services are positioned to meet the demand and requirements of sponsors." 

The following events prove that positioning is occurring: 					

In March, Covance purchased a clinical pharmacology company with a 50-bed facility in Basel, Switzerland. 

In March, ACM Global Central Laboratory acquired its long-time partner lab Pivotal Laboratories, based in the UK.  

In January, Quintiles partnered in a 50-bed Phase I unit in Hyderabad, India, with plans to go to 100 beds. 

In January, Cetero Research, a clinical pharmacology and bioanalytical CRO, announced a 100-bed facility in San Antonio, TX, specifically for clinical trials in healthy diabetic and obese subjects. 

And, last August, the harbinger of both the new strategic model and the early phase drug focus, Covance and Lilly's agreement whereby Covance acquired Lilly's early drug development campus in Greenfield, IN. As part of the agreement, Covance will provide the drug-maker with a range of services over the next 10 years for $1.6 billion.

Articles

News

A look at the contract research organization market and its trends toward early phase services.

CROs Head for Early Phase Growth

, MD, medical director of Metroplex Clinical Research Center (Dallas, TX), have both been elected as the newest members of D.L. Anderson's Board of Directors.

• After serving as head of preclinical development for Medigene AG (Munich, Germany) for the last nine years, 

 will now take on the position of head of preclinical development and project management at 

• The role of business development executive at 

 (Wilmington, DE) North American location will be filled by 

, who joins the company after a seven-year tenure at Almac (Craigavon, UK). 

• Formerly holding senior positions in professional services and implementation management, 

 will now serve in the newly developed position of senior director, professional services, at 

• With more than 20 years experience in virology drug development, 

 (Raleigh, NC) principal strategist of Infectious Disease. 

 Editorial Advisory Board member and executive director of the Good Clinical Practice Alliance, Europe, 

 (Bourne End, UK) annual spring conference and exhibition working party. 

• Of the 12 nominees for this year's European Inventor of the Year award, four come from the pharmaceutical arena: 

To ensure compliance with EU Good Manufacturing Practices, the 

(Bilthoven, The Netherlands) has chosen to use 

 (Holmdel, NJ) TrackWise Enterprise Quality Management solution.

Extending its platform of QA data validation solutions, 

 (Phoenix, AZ) to utilize the company's ranging suite of project planning, document management, regulatory submissions, and collaborative authoring.

In an attempt to quantify the effectiveness of its cartilage repair device, 

 (Rochester, NY) to provide blinded data analysis of quantitative magnetic resonance imaging (MRI).

 (Brentwood, TN) will provide recruitment services for a national study on Hepatitis C that explores an investigational drug's effectiveness as a mono-treatment as well as an add-on treatment option for the condition.

 (Philadelphia, PA) announced it will now offer its medical device operations in the United States.

 (Research Triangle Park, NC) central labs to receive the acknowledgment, the company's facility in Buenos Aires, Argentina, was recently accredited by the College of American Pathologists (CAP).

, part of the SGS Group (Geneva, Switzerland), recently sponsored one family's participation, the Michels, in the North Pole Marathon, which raises money and awareness for Cystic Fibrosis research.

 (Wilmington, NC) immediate entry into Central and Eastern Europe, including Romania, Bulgaria, Serbia, and Croatia, is an agreement that it will acquire 

 After working together under an exclusive alliance and maintaining a long-time partnership, 

 (Rochester, NY) is finalizing its acquisition of 

Community

Industry news focusing on the people and organizations who work in the clinical trials profession.

Business and People Update May 2009

What's worse than spending millions of dollars on a clinical trial only to discover your findings are wrong? Learning too late that those errors could have been prevented. Health survey administration errors, data entry mistakes, and mathematical miscues are just a few of the common missteps during clinical trials that have cost companies millions and delayed the introduction of new drugs. In one well-known population study, for example, the first question of the survey was inadvertently left off when the questionnaires were reprinted. 

In another case, the questionnaire responses in a large clinical trial were mislabeled, leading to significant errors in scoring. Also, too often, companies try to write their own survey scoring programs. 

Even companies with experience and expertise find the task of coding and reproducing scoring algorithms extremely challenging. With so much depending on accurate data, taking such a do-it-yourself approach can be very risky. 

When data and scoring errors occur, the impact can be far reaching. You could miss out on a huge opportunity if bad data masks a benefit of your drug that could open up a new, unexpected market. 

Fortunately, there are tools available that can help protect the time and money that you invest in health surveys. 

Software exists that standardizes the scoring and processing of data and tests for data entry and coding errors. This software can simplify the process and provide reliable results you can trust. 

Since the quality of your data is so important to your success, look for a scoring solution that can evaluate data quality and alert you to any data problems that exist. 

Since humans are administering and completing the surveys, there are a number of things that can go wrong during the survey process. Questions can be skipped or answered incorrectly. The survey might be administered improperly or survey responses could be keyed into a database incorrectly. Make sure the scoring software you eventually choose can recognize these types of problems so that they do not corrupt your results. 

When a partially completed survey is discovered, some of today's scoring programs can actually help fill in the blanks. Before you purchase your scoring software, find out if it includes this feature. If so, you may be able to save substantial time and money in the long run. 

When deciding on a scoring solution, ask yourself whether you want to install and run the software at your company or if you want a patient reported outcome (PRO) expert to handle it for you. This person can help interpret your data as well. 

If you decide to go the PRO route and you want the convenience of submitting your data on the Web, choose a scoring solution that offers that option. 

On the other hand, if you have data privacy and security concerns and you want to score your data within the confines of your own software system, make sure the scoring software you're thinking about purchasing can be easily integrated into your own system. 

Health surveys provide invaluable insight and information throughout the clinical trial continuum. Therefore, be sure the information you collect tells the right story. This is achieved by making wise choices about how you are going to score and analyze your data. 

MA Vice President and Senior Scientist QualityMetric Incorporated 

A Closing Thought

With so much depending on accurate data, taking a do-it-yourself approach to scoring can be risky.

Survey Says: Get the Data Right

It would seem senseless to start the construction of a house without a blueprint, prepare an unfamiliar dinner without using a recipe or start a season aiming for a championship without a play book. Unfortunately in the biopharm industry, far too often such conventional wisdom is lost in the haste to deliver now, and the consequences can be disastrous. 

Product development challenges have never been more formidable. Recent economic downturns, along with increasing concerns regarding the safety of marketed drugs,

  have captured a lot of attention. With decreasing investment resources,

  and stiffening competition for subject and site recruitment,

  today's market will not tolerate missteps. 

Gone are the days of seeding trials, exploratory fishing expeditions, do-over trials, and the like. Today, success is predicated on implementing an efficient and effective program, while calling for optimally designed trials that are conducted correctly the first time. Strategic development planning is the means to this end. 

Ideally, strategic development planning should begin with early discussions prior to the start of any activity. The  "guidebook" for planning is the integrated development plan. And this plan incorporates all activities related to the entire development program. 

As the goal for development is to obtain marketing authorization with a desired indication statement and label claim(s), it is critical that all activities be aligned and integrated to serve that purpose. In this regard, the development plan is an excellent tool to maximize efficiency and pull together supportive information, while also serving to coordinate efforts. It ensures and reminds stakeholders that all activities funnel to a common purpose. 

Despite the fact that early strategic planning requires an up-front investment of both time and money, the benefits reaped during the development program far outweigh the initial investments. 

An elegant development plan demonstrates a level of thoroughness that is appreciated by regulators and investors alike. Much like an insurance policy, a development plan offers reassurance to stakeholders, providing a level of security that may be fostered over time.

The utility of a development plan lies in its ability to organize and integrate a multitude of information in one place. More than simply a list of tasks to be completed, it provides a temporal link of activities occurring across disciplines. This is of value not only with regard to streamlining activities, but also in terms of contingency planning. 

The integrated development plan is essentially composed of several sub-plans, among these are:  

Chemistry manufacturing and controls (CMC) development plan

Regulatory strategy/target product profile (TPP)

The preclinical, CMC, and regulatory plans are designed to support a clinical program through each study. Therefore, considerable attention must be given to their timing. For example, it is important for the preclinical and CMC plans to precede sufficiently the clinical plan to ensure there are adequate toxicology data, as well as sufficient investigational product, to support planned preclinical and clinical studies. The integration of all these activities can only be accomplished with careful risk management planning. 

Marketing approval is granted based on the ability of the applicant's data to support the proposed indication and label claims. Therefore, it is imperative that each plan be crafted and constantly reevaluated against the marketing claims. Unfortunately, with personnel turnover, shifting priorities, and the occasional catastrophe, it is all too easy to get bogged down in the details and lose sight of the objective. 

This is where a solid development plan can mean the difference between failure and success. In summary, it is:  

A unique, comprehensive, global road map for the development of the compound

A way to identify key decision points throughout the development, also known as go/no-go decision points

One place where all activities, regulatory strategy, and commercial considerations are laid out

Adaptable as new information about the product, indication, and regulatory environment becomes available

A critical "living" reference for the development team and other stakeholders

In addition to being something that is not quickly or easily put together, the integrated development plan is also not: 

 While this may be a major focus, there are other significant activities supporting the clinical program that need to be considered. 

 Ongoing review of the plan is needed, as data from studies and other activities become available, new regulatory guidance and requirements emerge, or new information about the target indication becomes known. 

Written or maintained by only one person.

 The complexity of the plan requires ongoing assessment and input from the entire team to fully appreciate the impact of new information. 

Successful strategic development planning is done by a team of experts, who should include but not be limited to the following individuals:  

Several core questions should be addressed at the outset of strategic planning. The answers will help define the scope and breadth needed for the integrated development plan. 

Once the desired target indication statement and proposed label claims are determined, the next step is to work backward with the end in mind to shape the program based on logistical and operational considerations. The questions that should be addressed include, but may not be limited to:  

Which elements are required to support the proposed label claims (i.e., critical path) and which are nice to have?

What resource and time constraints must be considered?

Feature Article

An integrated product development plan designed early increases the odds of on time success.

Strategy First

In late March, the House Subcommittee of Oversight and Investigations released the results of its three separate sting operations carried out in an attempt to uncover malpractice within the IRB industry. These were conducted by the Government Accountability Office (GAO). 

 Industry Response to IRB Investigation			

One of the operations, which entailed submitting a fake and risky study to IRBs for approval, found unanimous authorization from only one of the three targeted companies: Coast IRB (Colorado Springs, CO).  

On April 14, FDA issued Coast a warning letter, and the offending company pledged to postpone taking on any new studies as well as allowing any new subjects to be entered into already approved trials. Meanwhile, it also announced it would undertake sweeping reforms designed to exceed the level of protection required by existing law, it claimed in a statement provided by the company's public relations group. 

In "the next 30 days this company will be completely different, said Coast chief executive officer Dan Dueber, "operated by different people, relying on different standard operating procedures, even having a different name." However, at press time, Coast instead opted to cease operations and shift ongoing trials to other IRBs. 

This extensive investigation involved a fictitious lead researcher with a false medical license and resume, a fake FDA marketing approval, a fake protocol for a fake medical device from, you guessed it, a fake company. 

While some risk that subjects face when participating in a clinical trial may be unavoidable, the question remains: How much risk should be tolerated? 

Apparently not as much as the GAO's phony medical device study proposed, which was to pour a full liter of liquid into a woman's abdominal cavity after surgery to assist with healing. 

GAO's fake protocol was based on an actual study for a product that FDA ultimately withdrew from the market because of deaths and infections among patients, Subcommittee Chairman Bart Stupak said in a statement. 

The Subcommittee initially began looking at IRBs after discovering issues related to a clinical trial of an Aventis drug, Ketek, in 2007. And according to an aide to Stupak, "The Subcommittee knew from the Ketek investigation that there were problems with IRBs. This GAO study helped determine how widespread the problems were, as well as a realistic look at how IRBs operate." 

GAOs choice of the three targeted IRBs was based on an online search of independent IRBs that had the least initial paperwork requirements for protocol submission. 

"Anytime you look at the low end of a bell-shaped curve you will find problems...Essentially they reviewed the low-hanging fruit of the industry," observed Erica Heath, president of Independent Review Consulting (Corte Madera, CA), and 

 Editorial Advisory Board member. "Even then two of the three IRBs did not approve the study." 

Along with the IRB investigation were two others: The Department of Health and Human Services (HHS) was fooled into registering a fake IRB, and GAO filed an assurance for federal funding with a fake company, which was granted. 

The issue with these operations, according to Heath, is that "registration was not intended as an approval process. If the Subcommittee had spoken with OHRP about what they do and their processes, they could have uncovered that information without having to carry out the bogus registration." 

As for being granted assurance, Heath explained that this is simply an agreement between the sponsor and HHS that they will conduct their activities using subjects in an ethical manner, abiding by current regulations. Once again, she noted, this in no way was intended as a form of approval of the sponsor company. 

She goes on to raise the question, which perhaps is lingering in many IRB professionals' minds: "What was the ultimate goal of this entire operation? To make someone look bad, raise or make a point that more money for FDA and OHRP is needed to support the system?" 

				While most of industry seems reluctant to comment on this touchy subject, 83% of respondents to an 

 online poll did reveal they felt the sting operation was justifiable, as opposed to the 17% that felt it definitely was not.—

Congressional sting operations put the IRB industry under the spotlight.

IRB Found Coasting Through

Leaders from both sides of the Atlantic shared the stage in late March to provide DIA EuroMeeting attendees with an update on the U.S.-EU Transatlantic Administrative Simplification Plan. Speaking on behalf of their agencies were Thomas Lönngren, executive director of EMEA, and Murray Lumpkin, MD, FDA's deputy commissioner for international programs.  

 FDA's Dr. Murray Lumpkin described the transatlantic initiative as a "relationship that began in earnest 10 years ago." 

From the sound of things, it's smooth waters for the Transatlantic plan, which is taking the relationship to the next level. This summer, as part of an employee exchange program, FDA will send one staff member to London to set up office at EMEA headquarters. The two-year, permanent position was awarded to Janice Soreth, MD, deputy director, medical products, Europe/OIP/FDA. 

Soreth's EU counterpart, who will head to the American capital, has not been selected yet. Lönngren joked that a decision would be made once the giant package of rules on his chair was read, eventually predicting this autumn as the earliest EMEA would get the ball rolling. 

Amidst humor, he made his feelings clear about the exchange, calling it a "milestone, where we are bringing two agencies together."  

The amiable Lumpkin expressed excitement over the upcoming employee transplants. But no sooner did he take the podium than he told the audience he wanted them to walk away aware that both agencies have "quite extensive" relationships beyond the Transatlantic plan. "[It's] a very important one," he said, "but in reality, we have relationships at a process level that go on at a daily basis and go on at the technical level as well"—and these relationships, according to his calculations, result in 1000s of document exchanges every year. 

Nonetheless, Lumpkin admits nowadays it's hard to imagine not working with the EU on a business level with the Transatlantic plan, which requires both sides follow two rules in their quest for simplification. They cannot take on projects that reduce public health protection or projects that require any changes to legislation. 

What they have taken on so far does please pharma, says Ali Harrison, vice president of European regulatory affairs at AstraZeneca, who provided a personal perspective from industry on the U.S.-EU simplification plan. 

Industry is extremely supportive of all activities, Harrison told the audience, and interested in dialogue. "This is a great forum to share information," she said, referring to DIA, "but we'd like to see more engagement." 

 Personally, she would also like to see—"just suggestions"—projects in pediatric applications, risk management plans, and patient reported outcomes (PROs). "Anything that simplifies things is welcome," Harrison said, adding that "it would be great if one set of responses would be sufficient for both agencies."

 In the meantime, both sides say they will continue to figure out ways to take the relationship further in their transatlantic endeavor to improve public health through simplification.—

For an in-depth listing of projects, visit 

The U.S.–EU Transatlantic Administrative Simplication Plan continues on the road of development.

Regulatory Relations

New features address complexity of global submissions standards

has updated its global submission document authoring template suite to include over 230 templates. 

StartingPoint 3.2 includes the following enhancements: Global Configuration File for Document Information Fields that allow for global settings to be preconfigured to minimize manual entry and ensure consistent naming conventions; Enhanced Physician's Labeling Rule Functionality, which offers flexibility in column format for editing and for delivering prescribing information; new templates that support ANDA submissions; and Table and Figure Numbering per Section that provides the option to number tables and figures either by document or by section. 

Octagon Research Solutions, (610) 535-6500, 

Secure document storage for SOPs available

 a provider of Enterprise Content Management (ECM) solutions for the pharmaceutical, biotechnology, and medical device sectors, announces the addition of the new g-SOPs tool to its g-docs portfolio of document management solutions. 

The software facilitates the creation, management, and storage of controlled documents related to Standard Operating Procedures (SOPs). g-SOPs allows users to create and manage SOP documentation and trigger automated workflows, including review and approval processes. Within g-SOPs, users can publish approved SOPs to the document library and access a full audit trail and complete document history. All SOPs and related documentation are securely stored within the g-SOPs module of g-docs. The g-SOPs tool is FDA 21 CFR part 11 compliant.  

Major version upgrade includes new module

 announced Version 3.5 of its NextDocs Regulatory Document Management System. The upgrade includes a new module called the Clinical Documents Module that joins the SOP Management Module and the Regulatory Documents Modules as a component of the NextDocs Document Management System. 

The solution addresses collaboration and document sharing between sponsors, investigators, site monitors, and vendors and includes support for scheduling and tracking of site monitor visits, documentation of investigational product protocols, and support for study documents such as investigator brochures, study protocols, 1572s, informed consent forms, and investigator CVs. The Clinical Module sits on the NextDocs Compliance Platform. 

eShowcase

The latest eclinical software in the clinical trials industry.

eClinical Software: May 2009

Market conditions are ripe for the formation of alliances between sponsors and service providers. Facing a difficult global operating environment characterized by capacity constraints, rising portfolio demands, cost containment, and depressed revenue and profitability, biopharmaceutical companies are looking to extract consistently higher levels of efficiency and performance from their contract research organizations (CROs) and investigative sites. 

Alliances are no longer simply hopeful concepts; they are emerging structures whose impact on development performance is not yet known. They hold promise, however, in delivering higher levels of performance and efficiency, fewer management surprises, and cost reduction. 

Several sponsors have been supporting alliances with their CROs for a number of years (e.g., Daiichi-Sankyo, Bristol Myers Squibb, Elan Pharmaceuticals). A growing number of biopharmaceutical companies now report that they are planning to include alliances among the various outsourcing relationships that they will support (e.g., Otsuka Pharmaceuticals, Merck-Wyeth). 

At the present time, sponsor–CRO alliances with investigative sites are nascent. Only a small number of organizations (e.g., Sanofi-Aventis, Quintiles) have announced or have implemented plans and programs to support these alliance relationships. 

Underlying attributes, drawing primarily from the more evolved sponsor–CRO alliances, offer insight into new ways that these relationships might operate and the support required to nurture them. 

Traditionally, sponsors have contracted with their CROs on an ad hoc per project basis, driven by the need for personnel capacity to perform a given task or function. Under these transactional relationships, sponsors typically interact with a large number of service providers, including contract full-time staff and CRO staff. 

Sponsors typically solicit a minimum of three bids and select the lowest bid-provider. In many instances, sponsors have established preferred lists of specialty and full-service CROs in order to expedite selection and contracting and to secure more favorable services pricing. Although cost control is a major goal of transactional relationships, frequently CROs must perform out-of-scope activity on their projects resulting in cost overruns. 

Once CROs are selected, sponsors tend to micromanage the relationship in order to oversee the project team, and to ensure communication and coordination, and adherence to the sponsor's own standard operating procedures. Middle managers typically serve as the primary parties involved in outsourcing planning and governance. 

Functional tasks outsourced in transactional relationships are typically those that are performed once the development plan and protocol are completed. Recently, a number of drug development companies (e.g., Wyeth, Amgen, Lilly) have supported broad functional outsourcing. These relationships give greater responsibility for an entire function to a single CRO, but that outsourced function still must be integrated with the rest of the sponsor's development activities. For this reason, full functional outsourcing appears to be an interim or "bridge" step toward a "true" alliance. 

Alliances between sponsors and CROs begin with a detailed and honest assessment of the sponsor's core competencies in order to determine what functions are performed best in-house versus those that can be best undertaken by a CRO. Most experienced CROs have managed a much higher volume of activity in many areas of clinical research than have many of the sponsors with which they partner. 

The goal of alliances is to build a team of internal and external resources to perform complementary competencies in order to take full advantage of the expertise and operating efficiency that each member brings to the table. Under alliances, sponsors look to retain senior-level expertise, but they reduce the number of internal staff involved in those functions deemed most suitable for outsourcing and they reduce the amount of project oversight, thereby promoting higher levels of autonomy and accountability. 

The identification and selection of alliance partners is a critical success factor and is based on many criteria, including CRO-company expertise, capacity, positioning, and culture. Once a sponsor has determined the scope of work that will be undertaken, and has selected a partner CRO, the companies together constitute a senior-level committee. 

The executives on the committee, from both sponsor and CRO companies, get together periodically (once or twice annually) to review prospectively the portfolio of projects on which they will partner. 

Governance in alliances is a shared responsibility. The sponsor and the CRO rely on a set of Coordination Operating Procedures (COPs) to ensure that each party's own respective SOPs is consistent, integrated, and compatible. When there are conflicts to resolve, they are addressed by the senior level committee. This approach affords the CRO greater autonomy to leverage its expertise, operating practices, and efficiencies. 

Under alliance relationships, sponsors tend to work with only a few full-service CROs who assume the responsibility of managing niche and specialty service CROs. As a result, the sponsor devotes little time to managing and coordinating a disparate collection of contract service providers. 

Attributes of sponsor/CRO–site alliances are analogous to those described in sponsor–CRO alliances. Instead of having to select many individual investigative sites based on each study's requirements every time clinical testing is about to begin, a select number of investigative sites are identified and engaged, in advance, based on the needs of the sponsors or CRO's portfolio of clinical trials. Selection of investigative sites will be intensive, but it will lead to the establishment of long-term recurring sponsor/CRO–site alliances. 

In alliance relationships, sponsors and CROs do away with ad hoc budgets and contracts. Instead, each year investigative sites renew a longer-term contract and negotiate a budget based on the portfolio of expected annual clinical studies. In order to ensure that sites allocate the best resources for alliance-based projects, sponsors and CROs will likely need to guarantee a certain amount of annual work. 

Whereas most communication between sponsors/CROs and investigative sites can be sporadic, in alliance relationships it is critical that communication be seamless, bi-directional, and integrated. Eclinical technology solutions are critical infrastructure elements supporting sponsor/CRO–site alliances. 

Another critical infrastructure element that sponsors and CROs must provide their alliance partners is centralized, proactive support resources to assist their investigative sites in patient recruitment and retention activity, regulatory compliance (e.g., filings, reporting) and operational efficiency (e.g., financial controls, facility management). Traditionally, sponsors and CROs have provided support to their investigative sites in a reactive and fragmented fashion. 

Similar to sponsor–CRO alliances, governance and conflict resolution between sponsors/CROs and sites is a shared responsibility where both parties contribute dedicated and senior staff to oversee the portfolio of projects. 

Sponsors expect to always be managing a mix of relationship structures that includes alliances and task-oriented, project-based relationships. However, sponsors anticipate that alliances will become far more prevalent during the next three to five years. 

Although alliances will not likely result in lowest bid providers, in theory, efficiencies gained in study start-up, ongoing project communication and close-out; minimization of out-of-scope costs; and centrally supported performance improvements should far surpass short-term cost savings.  

Service providers striving to establish alliances will need to possess a strong willingness to share the economic risk of supporting fewer sponsors and the operational risk of accepting greater accountability and responsiveness for communicating and resolving problems. With higher assumed risk comes higher upside for service providers, which may include performance and commercialization incentives. 

Alliances will also need to establish operating policies to support greater transparency and open communication and dedicated staff familiar with and motivated to make alliances work. Lastly, they will require integrated and compatible communication, management, and support systems. 

For those service providers who are not suited to enter—or choose not to enter—alliances, there are strategic opportunities to meet the specialization needs of these emerging relationship structures. 

Alliance fever is here. It represents a positive step in the evolution of more effective collaborations facilitated by the current economic climate. 

 MBA, is a Senior Research Fellow at the Tufts CSDD and Chairman of CISCRP, both in Boston, MA, email: 

Clinical Trial Insights

Out of necessity, providers may finally become valued strategic partners.

A Compelling Need to Usher in Alliances

Senior clinical researchers have reacted strongly to an analytical article and commentary that are deeply critical of the drug evaluation process. 

Professor Silvio Garattini, director, Mario Negri Institute for Pharmacological Research in Milan, and Sir Iain Chalmers, editor, James Lind Library in Oxford, have called for major changes in drug evaluation.

  Their controversial views have been supplemented by a commentary from Michael Tremblay, PhD, partner of Tremblay Consulting, Ashford, UK.

"As a citizen and at times a patient or a parent of an ill child, I resent the tendency of the authors to represent patients and prescribing doctors as dumb victims who are stupid enough to be lured into morally and medically wrong behavior by a devious industry," said Beat Widler, PhD, a clinical quality assurance executive from Switzerland. 

"This is profoundly dishonest and might be acceptable when coming from a blinkered political activist who is on an anticapitalist crusade. I consider myself as a man of ethics with firm moral principles, not an instrument of greedy fat cats who are just out to make a quick buck," Widler added. 

It is cheap propaganda to infer that the wrong doings that have happened on the margin of clinical trials is common practice. The authors overlook the fact that major disasters in the field were caused by nonindustry researchers. Also, the new medicines have cured many serious illnesses, and pharma has played a leading role in developing today's essential medicines, he noted. 

"The authors are right in affirming that our industry has a credibility problem, but the solution is not to replace effective discovery and development processes but to better engage the stakeholders in a fair and balanced debate. The pariahs of this article, health authorities and industry, must be partners in this," said Widler. 

Garattini and Chalmers ask the right questions, but not everybody will agree with their answers, according to Professor Gerfried Nell, president of the International Federation of Associations of Pharmaceutical Physicians. Nell thinks the drug development process needs major improvements but believes that some of the shortcomings, such as restricted patient populations, cannot be blamed solely on industry. 

"Transparency is obviously the key to building trust," he said. "However, I am not so sure that further improvements in this direction should be enforced by law. It is probably better to build public pressure in order to change attitudes." 

Overall, the authors present a weak case, noted Uwe Gudat, MD, 

 Editorial Advisory Board member and medical director in the office of the chief medical officer at Merck Serono. The many treatments developed by industry are witness to the fact that it is providing a public service. Numerous innovations that have revolutionized medical practice are off patent, allowing patients access to fairly inexpensive therapeutics. 

Dr. Gudat supports more patient involvement in clinical research, but fears it may highlight the conflicting interests of stakeholders. Patients are often keen on small improvements in well being that outcome-focused physicians discount as unimportant. Similarly, patients may favor treating minor ailments, leading to what may be seen by some as disease-mongering.—

S. Garattini, I. Chalmers, "Patients and the Public Deserve Big Changes in Evaluation of Drugs," 

I. Tremblay, "Risks of Doing as the Romans Do," 

Global News

Industry professionals address critical commentary of the drug development process.

Industry Reacts to Bad Review

The economic stimulus package approved by Congress in February provides more than $1 billion to support research on competing medical treatments. Although a fairly minor piece of the larger $789 billion American Recovery and Reinvestment Act of 2009 (ARRA), the provision set off a firestorm about using comparative study results to limit coverage of more expensive medicines. 

				Conservatives raised the specter of "government rationing" and "cookbook medicine."

Comparative effectiveness (CE) enthusiasts, including Obama administration officials, countered that more and better information about which medical products and procedures are most effective can improve care and cut unnecessary spending. But a White Paper last year from the Congressional Budget Office looked to CE research to "provide a basis for applying costly new technologies only when they are likely to confer added benefits." 

The final ARRA legislation compromised by stating that Congress does not intend for CE research to be used to "mandate coverage, reimbursement or other policies for any public or private payer." Observers noted, however, that once CE research results are available to the public, health plans and payers can use the data as they see fit. 

In any case, the government-funded CE research program opens the door for the federal government to play a larger role in selecting and shaping comparative assessments. Instead of establishing a new, independent entity to carry out CE research, as some advocated, the stimulus package divides $1.1 billion among three arms of the Department of Health and Human Services (HHS). 

Government funding slated to boost studies comparing medications to other treatments.

Applied Clinical Trials-05-01-2009