the eu market for phase ii ib & iv studies

Summary Report – February 2004

PARIOFORMA LTD 55 Princes Gate Exhibition Road London SW7 2PN United Kingdom Tel: +44 (0) 20 7225 3538 www.parioforma.com

PARIOFORMA

http://www.parioforma.com/

PARIOFORMA

2 Parioforma Ltd – 55 Princes Gate – London SW7 2PN – United Kingdom

www.parioforma.com

We would like to thank the following companies for their time and assistance with this research:

Altana Pharma

Almirall

Amgen

AstraZeneca

Aventis

BMS

Elan

MSD

Novo Nordisk

Novartis

Organon

P&G

Sanofi Synthelabo

Serono

Schering AG

Wyeth

Yamanouchi

Covance

ICON

Inveresk Research

MDS Pharma Services

Parexel

Quintiles



PARIOFORMA


www.parioforma.com

Ph IIIb

Phase IIIb is the period between submission for approval and receipt of marketing authorization.

Phase IIIb studies are conducted to increase patient exposure – e.g. to provide additional data as requested by regulators at the time of approval.

In addition, studies can be conducted to provide information that can be used to promote the drug after the granting of a

product license, by studying special populations, special circumstances, new indications, quality of life, etc.

Phase IIIb is typically centrally coordinated, multi-national and involves large numbers of patients.

Ph IVa

An emerging segment.

Phase IVa is initiated after marketing authorization is granted.

Trials are typically global or multinational, involve large patient numbers and address global/multinational issues – e.g. safety, label and product lifecycle issues.

Ph IV

Phase IV is initiated after marketing authorization is granted.

Traditionally, phase IV studies in Europe have been localized to support local market development – the primary focus has been commercial rather than safety.

Phase IV trials may be used to evaluate formulations, dosages, durations of treatment, medicine interactions as well as

patients from various demographic groups.

Localized phase IV studies typically involve smaller patient numbers.

Studies that are primarily observational or non experimental are frequently called post marketing surveillance.

Ph V

Post marketing surveillance is sometimes referred to as Phase V.

Phase V remains outside the scope of the new EU Clinical Trial Directive as long as studies remain non-interventional.

For the purpose of this study Phase V has been included as Phase IV.

§ Based on respondent interpretations of operational activities



PARIOFORMA

4


PARIOFORMA


www.parioforma.com

Unlike the US, the European pharmaceutical market is not a single market driven by free competition, it remains complex and fragmented:

◦ pharmacos can utilize harmonized central registration procedures; but

◦ national regulatory, pricing and reimbursement policies demand localized approaches for each EU country;

◦ differences remain in:

culture;

language;

public and government attitude to healthcare; and

clinical practice.

For the pharmaceutical company operating within the European Economic Area this transpires into:

◦ delays in market access for new products which vary widely from country to country;

◦ government price controls in almost every Member State;

◦ delays in pricing decisions which vary by country;

◦ wide price differentials across Europe which lead to artificial parallel trade flows;

◦ a high cost in replicating efforts country by country – notably in the post marketing environment.

This fragmentation will persist despite harmonization attempts as each country looks to protect its own national self-interest above European ideals – the principle of “subsidiarity”.



PARIOFORMA


www.parioforma.com

European enlargement is set for May 2004:

◦ first wave EU acceding countries include: Czech and Slovak Republic’s, the Baltic’s, Poland, Hungary, and Slovenia;

◦ second phase accession countries (2007) include: Romania, Bulgaria, Albania, Serbia, Bosnia-Herzegovina, Macedonia, possibly Croatia.

The CEE countries face problems regarding the adoption of EU legislation lacking the institutional structures and capacities to sufficiently implement and enforce European regulations.

More importantly, there are funding and skills issues to be overcome.

Decrees and modifications to existing laws are still being implemented in most cases, although some governments are seeking delays, or derogations, to the implementation of EU pharmaceutical regulations with the aim of assisting local manufacturers and service providers.

Pricing and reimbursement approval in the CEE countries continues to be one of the major barriers to new product introductions – tending to be over-complex, bureaucratic and lacking in transparency.



PARIOFORMA


www.parioforma.com

Of the first wave acceding countries:

◦ Czech Republic, Hungary and Slovenia are all relatively well advanced having proper regulatory systems in place;

◦ Poland on the other hand remains “muddled” and “opaque”.

Respondents indicated that there would be much confusion during a prolonged transition period while acceding countries “get up to speed” with the rest of Europe.

EU Eastern expansion is therefore expected to add further complexity and bureaucracy, but cannot be ignored as these are growing markets that will continue to attract investment.

However, the CEE will continue to be an attractive area in which to conduct clinical trials due to the high quality of investigators, high quality of data and excellent patient resources – as evidenced by the amount of clinical spending in the region.

$450

$325

$90 $75

$10

$73

$24 $20

$0

$250

$500

$750

CEE Latin America Asia-Pacific ME/Africa

1998 2002

Source: PhRMA

Clinical Spending in Ascending Regions



PARIOFORMA


www.parioforma.com

The Pharma industry is being forced to become more commercially driven, more cost conscious and to maximize its ROI – it is becoming increasingly challenging to sustain the “blockbuster” model.

Several factors contributing to the harsh environment are in fact driving increased Phase IIIb and IV:

◦ narrowing avenues for drug discovery making NCEs more difficult and expensive to come by;

◦ longer and more expansive development projects coupled with shorter product exclusivity times;

◦ therapeutic markets are becoming increasingly crowded; and

◦ patients, physicians and healthcare providers have become more skeptical about the value of approved drugs, especially when they are more expensive than older or generic products.

An approved drug is therefore an asset, an asset for which pharmacos are trying to create as much “value” as possible for as long as possible.

In today’s fiercely competitive therapeutic markets it is more important than ever for a company to differentiate its product - today, regulatory submission and approval of a new medicine is only the starting point.

Effective and timely Phase IIIb and IV studies can provide the means to develop and refine differential competitive advantages and to block and defend against competition.

Today Phase IIIB & IV studies are increasingly used by pharmacos to maximize the length and value of the product lifecycle.



PARIOFORMA


www.parioforma.com

Marketing authorization holders (MAHs) should ensure that they have an appropriate system of pharmacovigilance in place in order: ◦ to assure responsibility for their products on the market; and

◦ to ensure that appropriate action can be taken, when necessary.

This includes the MAH having at its disposal continuously at least one appropriately qualified person responsible for pharmacovigilance available at all times within the European Economic Area.

It also requires the establishment of a system for the collection, preparation and submission of safety data to competent authorities. Systems should be capable of: ◦ Expedited reporting;

◦ Periodic safety update reporting;

◦ Responding to requests for information from competent authorities;

◦ Handling of urgent safety restrictions and safety variations;

◦ Continuous monitoring of the safety profile and notifying competent authorities and health professionals of changes to the risk/benefit of products;

◦ Meeting CPMP commitments.

Pharmacovigilance data should be collated, and be accessible, at least at one point within the European Economic Area.

At the time of assessment of marketing authorization applications, competent authorities will consider requesting documentation demonstrating that a system of pharmacovigilance is in place.

Pharmacovigilance regulatory obligations are placed on all MAHs. The obligations are the same whether the MAH is an innovative pharmaceutical company, or a generic company.

It should be noted that enforcement action for pharmacovigilance is within individual Member States.



PARIOFORMA


www.parioforma.com

The ICH E2E Step 2 guideline is expected to be ratified in 2004 and integrated into law in 2005.

The guideline is based on the WHO definition of the term pharmacovigilance as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug related problems.”

The guideline is intended to aid industry and regulators in planning pharmacovigilance activities – especially for the early post marketing period.

It proposes a structure for a “pharmacovigilance plan” and a “pharmacovigilance specification” and sets out principles of good practice for the design and conduct of observational studies.

The pharmacovigilance specification describes a method for summarizing:

◦ The identified risks of a drug;

◦ The potential for important unidentified risks; and

◦ The potentially at-risk populations and situations that have not been studied pre-approval.

The pharmacovigilance specification summarizes what needs to be addressed in the pharmacovigilance plan.

Industry and regulators have identified the need for better and earlier planning of pharmacovigilance activities before a license is granted:

◦ It is proposed that a pharmacovigilance specification and pharmacovigilance plan should be submitted at the time of license application.



PARIOFORMA


www.parioforma.com

◦ The pharmacovigilance plan must present all the intended actions for all individual risk issues and missing information.

◦ The pharmacovigilance plan must specify milestones for completion of studies and other evaluations, and for submission of safety results.

The pharmacovigilance plan is intended to be living document that accompanies the product through development. During the course of its implementation, any important emerging risk information should be discussed and used to revise the plan.

Routine pharmacovigilance will be required for all medicinal products, regardless of whether or not additional actions are appropriate as part of a pharmacovigilance plan.

Routine pharmacovigilance will include:

◦ Systems and processes that ensure that information about all suspected adverse reactions that are reported to the company are collected and collated in an accessible manner;

◦ The preparation of reports for regulatory authorities:

Expedited adverse drug reaction (ADR) reports

Periodic Safety Update Reports (PSURs)

◦ Continuous monitoring of the safety profile of approved products;

◦ Other requirements as defined by local regulations.



PARIOFORMA


www.parioforma.com

New pharmacovigilance initiatives give a framework for regulators to only grant marketing approval conditional on the continuous monitoring of a product’s safety profile based on a risk assessment and gap filling plan – the pharmacovigilance plan.

These initiatives are expected to reshape the pre- and post marketing environment.

The primary implications of the ICH guideline on pharmacovigilance for Pharma companies will include:

◦ The need to plan for pharmacovigilance activities throughout the product lifecycle;

◦ The need for a science-based approach to risk documentation;

◦ The need for effective collaboration between regulators and the Pharma company.

It is therefore highly recommended that company pharmacovigilance experts get involved early in product development – pharmacovigilance planning and dialogue with regulators should start long before license application.

Although the guidelines from the ICH are not (as yet) mandatory, pharmacos are already strongly encouraged to have a pharmacovigilance plan in place for submission.

Respondents reported that mandatory post approval safety studies required by the EMEA have been relatively rare but that there is now expected to be a significant rise in the number of post marketing safety studies carried out by MAHs – notably from 2005 when guidelines become integrated into law.



PARIOFORMA


www.parioforma.com

Whereas routine pharmacovigilance will be considered sufficient for the vast majority of products, additional safety studies can be expected for products:

◦ 1st in therapy class where risks are relatively unknown; and

◦ Lifestyle drugs where patients and regulators demand minimal risk.

The onus will now be on the individual companies to gather information relating to the benefits or risks of their product post approval, evaluation of this information should then be an on-going process in consultation with regulatory authorities.

Companies must report any changes is the risk: benefit ratio to regulatory bodies.

Therefore, underpinning the whole process of successful pharmacovigilance planning and implementation is a source of robust data derived from quality IT/data management systems.

Such systems will need to be integrated into the whole development process (not just at the beginning and end so typical of present) and used to provide sound feedback on which to base lifecycle management decisions as well as make revisions to the pharmacovigilance plan.

Traditionally pharmacos have tended to only use “single source” data. This will no longer be adequate in the new environment – they will now need to be able to pool all safety data arising from multiple sources into comprehensive and linked databases.

These linked systems should be set up to provide early warnings.



PARIOFORMA


www.parioforma.com

Robust and accessible information that has been collected in a consistent manner can be considered as “insurance” if things go wrong at a later stage – it will form the basis of sound risk management policy.

EU enlargement is expected to cause much confusion over the implementation of pan-European pharmacovigilance initiatives.

Accession countries do not have any systematic pharmacovigilance programs at present, concurrently they also lack the institutional structures and capacities to sufficiently implement and enforce European regulations. In the long-run all accession countries will conform to the European regulations but there will be a very grey transition period.



PARIOFORMA


www.parioforma.com

Until recently there has been no pan-European legislation which governs how clinical trials are conducted.

Such legislation as existed was national legislation, as a consequence of which there were significant differences in the requirements within each EU member state as to how clinical trials should be undertaken and controlled.

The EU Directive on Clinical Trials (Directive 2001/20/EC) was published on 4 April 2001 and must be implemented into national legislation by 1 May 2004.

The new Directive is the first time that statutory controls have been put in place to define the ways in which clinical trials are carried out in the Europe Union.

The Directive will harmonize standards for the conduct of clinical research across the European Union and compliance with Good Clinical Practice will become a legal requirement for all clinical trials.

“ Non-interventional trials” are excluded from the definition of a clinical trial.

One of the other major objectives of the Directive is that it sets out standards for the protection of subjects enrolled in clinical trials, in particular, incapacitated adults and minors.

In effect, the Directive is intended to protect participants in trials by the introduction of GCP principles into the regulation and conduct of clinical trials.

For the first time, the role of an ethics committee has been brought under statutory provisions.



PARIOFORMA


www.parioforma.com

The function of an ethics committee is to provide an opinion before a clinical trial starts. Only if the opinion of the ethics committee is favorable will the trial be permitted to start.

The legislation requires that the decision from the ethics committee must be supplied within 60 days of the date of receipt of the application. If the ethics committee requires further information to make a final judgment, the time taken for that further information to be supplied by the applicant is not included in the 60-day schedule.

For certain products (e.g. medicinal products for gene therapy and somatic cell therapy, or products containing a genetically modified organism), the ethics committee is allowed 90 days to consider its opinion. A further 90 days may be allowed for the opinion of the ethics committee if it considers it necessary to consult further.

The legislation has established a procedure to obtain a single opinion for multi-centre trials. If all the sites for the multi-centre trial are located within the same country, an ethics committee application is directed to the committee located within or covering an area in which the chief investigator for the trial is based.

If the locations of a multi-centre trial are in more than one EU member state, each member state is required to give an opinion on the acceptability of the clinical trial.

In addition, before any clinical trial can start, the sponsor must also submit a valid request for an authorization to the regulatory authority of the Member State(s) in which the trial is to be conducted.



PARIOFORMA


www.parioforma.com

Arguments that the Directive will reduce delays and complications for trials involving several sites in different countries seem most relevant for Phase III/IV studies.

For these late-stage trials, the Directive could contribute a single application format whose contents would be valid throughout the EU.

This is likely to be beneficial for sponsors by reducing the need to satisfy differing local requirements – therefore bringing time and cost savings.

Although the administrative processes are intended to be harmonized by the introduction of the new Directive, it was recognised at the outset of its drafting that there would remain significant differences in the way that clinical trials are actually conducted in each EU member state.

Had it been intended to harmonize clinical trial practices entirely across the EU, the European Commission would have had to introduce a regulation, which would automatically have been applicable in all member states. Instead a decision was made to introduce a directive, which has to be transposed into national legislation in each country.

The new Directive should harmonize the administrative processes, but the underlying practice and conduct of clinical trials will continue to vary across the EU – due to local interpretation.

Another aspect of the EU Directive is that it also implies a separation between investigator and sponsor roles – this in itself, is expected to have a huge impact on publicly funded trials and on academic medicine.



PARIOFORMA


www.parioforma.com

A “sponsor” is any entity which takes responsibility for starting, managing, and/ or financing a clinical trial.

In the UK for example, many clinical trials have been carried out in collaboration between universities, the National Health Service, research councils and charities.

In such cases, the sponsor would be the individual body that takes on this ultimate responsibility for the trial.

It is necessary for those involved in the conduct of the trial to determine and to agree upon who is the sponsor for a particular trial and for that nominee to be notified to the regulatory authorities.

With the increasing burden of checks and rising costs, few organisations have volunteered to act as sponsors and many, particularly the medical charities, have shown a distinct antipathy. Many are thinking of giving up conducting trials altogether.



PARIOFORMA


www.parioforma.com

The most welcome aspect of the EU clinical trial Directive is that it will provide a level playing field in terms of study set up across Europe although there is expected to be a “grey” transition period while things settle down.

However, a key concern arising from the Directive is the increased burden in terms of cost – notably for small and mid-tier companies who feel that the Directive is biased against them in this respect.

Respondents now expect a more conservative approach to study spending with fewer but more focused and perhaps larger multi-country Phase IV studies to improve resource efficiency.

This trend in itself is already driving increased centralization of post marketing work – this trend is expected to continue and gain momentum.

The new EU Directive is also expected to make post marketing a much more difficult environment in which to work. The need for more rigorous and scientifically driven studies will mean more constraints on the commercial component of post marketing studies bringing them more in line with registration studies.

In order to get a trial off the ground, sponsor companies are now going to have to convince regulatory bodies and ethics committees of the scientific value of the study which will involve far more planning and forethought than in the past.



PARIOFORMA


www.parioforma.com

Many respondents expressed a concern over the future of investigator initiated work as a direct result of the new Directive.

It is anticipated that pharmacos will pull out of supporting investigator sponsored studies. With the costs of investigator grants already high, companies have no incentive to pay more when they have no autonomy and no control over the data collected.

This is expected to have most impact in oncology where the reliance on investigator initiated studies is highest.



PARIOFORMA

21


PARIOFORMA


www.parioforma.com

Market Development

Regulatory

Reimbursement

• Market priming

• Product positioning

• Product differentiation

• Publications

• Customer exposure

• Physician experience & key opinion leader support (KOL)

• Market extensions – extend product lifecycle

• Communication

• Additional pharmacoeconomic studies

• Cost - benefit

• Clinical guidelines

• Formulary access

• Address gaps in clinical safety/ efficacy data

• Post marketing commitments

• Supplementary filing

• Pharmacovigilance monitoring



PARIOFORMA


www.parioforma.com

Phase IIIb has traditionally been centrally funded and coordinated – there has been no change to this strategy.

However, Phase IIIb is no longer used simply as a means to supplement or complete earlier work – i.e. to address “clinical gaps,” but is also being driven by the need to address commercial and marketing needs. More emphasis is now being placed on studies that not only achieve the widest possible label but that address product lifecycle issues prior to launch.

Phase IV in Europe has traditionally been affiliate driven in order to respond to local market needs. Affiliates have been very commercially focused, however the impact of the new EU Directive on clinical trials will create a more scientifically driven Phase IV – studies with a marketing bias will fall foul of the new Directive.

Pharma companies are taking a more centrally controlled and coordinated approach to Phase IV:

◦ impact of the EU Directive on clinical trials;

◦ greater emphasis on global labelling;

◦ pharmacos now have clearer more well defined outcomes in mind – driven by the need to focus on lifecycle management;

◦ rising study costs;

◦ the need to focus on efficiency and cut down on repetition;

◦ centralized studies can be larger and of longer duration – therefore in theory, the return on investment should be higher;



PARIOFORMA


www.parioforma.com

◦ implications of ICH guidelines on pharmacovigilance;

◦ the opportunity to gather data over a wider area;

◦ the need for a centrally controlled database and the ability to pool data.

The result is the emergence of what is loosely termed as Phase IVa - this refers to the large, centrally controlled and funded post marketing studies as opposed to the traditional view of Phase IV as local driven work.

Phase IVa to date has typically been safety orientated. Studies are often initiated in quick succession to Phase IIIb in order to be able to address market needs or the demands of regulatory authorities.



PARIOFORMA


www.parioforma.com

Minimum Label

Submission

Marketing

Approval

Market

Launch

Ph IIIb

Ph III

Ph IV

Maximum Label

Submission

Marketing

Approval

Market

Launch

Ph IIIa

Ph IIIb

Ph IV

Ph IVa

NICHE/TRADITIONALIST BLOCKBUSTER



PARIOFORMA


www.parioforma.com

The niche/traditionalist approach:

◦ the strategic goal is to get marketing authorization as quickly as possible;

◦ the label is minimum sufficient for authorization;

◦ gap between phase IIIa and commencing IIIb – to ensure all safety and efficacy data available from IIIa before commencing IIIb;

◦ minimum phase IIIb work;

◦ “follow up” work returned to post launch in phase IV.

This the traditional approach to late phase work is typical for smaller, more niche products – e.g. oncology. This behaviour is also typical of mid-tier pharmacos and biotech.

The blockbuster approach:

◦ “piggy-back” health economics and outcomes in phase IIb/IIIa;

◦ maximum label for authorization – global labelling approach;

◦ seamless transition from phase IIIa to IIIb – even overlap;

◦ seamless transition from phase IIIb to IVa – IVa safety orientated to address risk management/ pharmacovigilance;

◦ minimum gap between launch and local phase IV – need to protect product in every marketplace.

This more integrated approach is typical for high value products and is fast approaching the “model” behaviour for Big Pharma wishing to maximise the commercial potential of their products. The reward vs. risk for this “blockbuster” strategy is high.

The strategy adopted is driven by the type of drug and the market potential, therefore even Big Pharma will opt for a “safer” strategy for smaller products.



PARIOFORMA


www.parioforma.com

Due to increasing external pressures, Pharma companies are no longer relying solely on NMEs to meet growth targets – lifecycle management strategies are becoming as important as product innovation in maintaining and building market shares and revenues.

Emphases on “whole-life” product lifecycle management now reflects the need to work products “harder”.

Increasingly, crowded and competitive therapeutic markets mean:

◦ the need for greater product differentiation;

◦ pharmacos are thinking and planning more strategically;

◦ product management is becoming more “proactive” – the need to anticipate rather than react to market forces and competitor activity;

◦ greater efforts are being focused on market development:

to gain fast market penetration;

and early adoption.

Internal organizational improvements have facilitated this process. Cross-functional product teams have emerged in Big Pharma and are impacting on pre- and post-marketing protocol design by:

◦ addressing product lifecycle issues prior to launch – e.g. phase IIIb line/ label extensions;

◦ introducing commercially useful endpoints earlier – e.g. Ph IIIa rather than Ph IV.



PARIOFORMA


www.parioforma.com

Strategic Phase IV plans are being utilized as living documents that follow the NME through development from proof of concept onwards – an emerging concept for mid-tier companies but more robust in Big Pharma.

However, mid-tier companies have not moved as far or as quickly as “Big Pharma” in effective clinical-commercial integration to drive peri-approval market development.



PARIOFORMA

29


PARIOFORMA


www.parioforma.com

DRIVERS RESTRAINERS

•Increasing globalization and centralization of work

•Increasing complexity of trials

•Control of schedule, budget and timelines

•M&A activity leading to leaner organizations

•Ease of project management for larger, international trials

•ICH pharmacovigilance guideline – more safety work,

increasing data management demands

•EU Directive on clinical trials – increased workloads, GCP

requirements

•Control internal headcount

•Access to difficult patient populations

•Access to local knowledge and expertise

•Access to specific expertise

•The need to increase productivity – notably at affiliate level

•Increasing numbers of products coming to market

•Reduce internal bureaucracy – clear lines of responsibility

•Company attitude

•The desire to keep more scientifically driven and interesting

studies in house

•Ownership of the sponsor-investigator relationship

•The need for internal staff development

•Previous bad experiences

•Need for overall control

•Cost perception – cheaper in-house

•Perception of risk



PARIOFORMA


www.parioforma.com

Over one quarter of Pharma respondents indicated an increase in outsourcing in recent years due to internal strategy changes or as a means of managing growth. The major outsourcing driver being the trend towards larger, more centrally controlled studies – notably in the post marketing environment.

The level of outsourcing varies widely by company culture and phase of development. The table below summarises the average of replies provided by interview respondents:

Phase IIIb Phase IVa Phase IV

Big Pharma Mean 42%

Median 35%

Mean 45%

Median 45%

Mean 11%

Median 10%

Mid-Tier Pharma Mean 69%

Median 65%

Mean 70%§

Median 70%§

Mean 58%

Median 55%

§ Not fully active in this area yet – answers based on future expectations of outsourcing in this area.



PARIOFORMA

32


PARIOFORMA


www.parioforma.com

0

1

2

3

4

5

6

Quality

Capacity

Therapeutic Experience

Prior Experience with Vendor

Price

Proven Ph IIIb/IV Experience

EU Wide Expertise

Dedicated Teams

Vendor Reputation

Technical Expertise

Geographic Proximity

EDC Capabilities

Average of respondent ranking of

stated selection criteria – 6 =

high; 1 = low. NB: results are

directional rather than

quantitative.



PARIOFORMA


www.parioforma.com

Customer perception of vendor quality and the availability of capacity are prime concerns in the selection process.

Quality is a measure not only of the CRO operation in terms of service delivery but also a measure of the calibre of staff employed - key aspects of a quality vendor include the ability to deliver on time and on budget.

Second tier selection criteria include:

◦ relevant therapeutic experience;

◦ prior experience with CRO.

Satisfying these criteria evokes a level of comfort – prior experience in particular is an indication of quality.

More scientifically driven late phase work is expected to increase the need to select vendors with the appropriate therapeutic expertise.

Price is gaining in importance as pharmacos become more cost conscious, but it is not top of the list.

Due to the greater popularity of large multi-country trials across, EU wide coverage is becoming an important selection criteria.

Late phase work has traditionally been an RFP driven business leaving little opportunity for CROs to adopt a consultative role advising on study design and desired outcomes. However, things are now changing and some sponsor companies indicated that they are becoming more receptive to CROs taking a more proactive approach in this area.



PARIOFORMA

35


PARIOFORMA


www.parioforma.com

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

Site activation & monitoring

Data collection & management

Patient recruitment

Registry design & database creation

Data analysis & report development

Investigator recruitment

Clinical trial supplies

Site selection

EDC

Study designPharmaco respondents were

required to rank the stated

service requirements

according to need: 6 = high; 1

= low.

The chart displays the

average of results.

NB: results are directional

rather than quantitative.



PARIOFORMA


www.parioforma.com

Top tier customer service requirements are:

1. Site activation & monitoring;

2. Data collection & management;

3. Patient recruitment.

Second tier customer service requirements are:

4. Registry design & database creation;

5. Data analysis & report development;

6. Investigator recruitment.

The late phase business has traditionally been RFP driven, this is reflected in the customer perception of service requirements – vendors are used in the main as additional “arms and legs” performing the functions for which internal resources are low.

Consequently, CROs have had little potential to offer any “added value” as seen in the low propensity to involve vendors in study design. However, the propensity to involve CROs in study design may well increase as Phase IV becomes more scientifically driven and more costly - an idea not shared by pharmacos as yet.

The increasing involvement of professional purchasing departments in vendor selection has resulted in a “metrics” orientated environment e.g. vendors are required to complete “bid grids” which dissect the global cost of the study into various line items which are then analyzed and used to compare prices between CROs.



PARIOFORMA


www.parioforma.com

Over the past 5 years study costs in Europe have risen steeply driven by:

◦ regulatory demands;

◦ increasing scope and complexity of Phase IIIb/IV;

◦ increasing overheads and investigator fees.

CEE has traditionally enjoyed a 30% cost advantage over the rest of Europe.

Labour costs are now rising in the region but it still remains a much cheaper environment in which to conduct clinical trial work.



PARIOFORMA

LONDON OFFICE ASSOCIATE OFFICES

Charles Rowlands Senior Partner 55 Prince’s Gate Exhibition Road London SW7 2PN United Kingdom Tel: +44 (0) 7803 907577 www.parioforma.com

USA Intrix Corp, Darien Connecticut

Eastern Europe

IMRP, Moscow

Brazil Intrix Corp, São Paulo

Japan TRN, Tokyo

RM Consulting is now part of Parioforma Ltd., an independent business consultancy headquartered in London, UK. Key benefits of working with Parioforma: Bespoke studies – tailored to client needs and

timelines.

Affordable research prices – makes your budgets go further.

High quality research – experienced science-based team, all with post-graduate science and/ or MBA qualifications and with 10-25+ years experience in Life Science and High Technology industries.

Unique problem solving approach – the team is highly specialised, but diverse in experience and background, enabling analysis of problems from different perspectives.

Strategic Pointers – helps clients better understand the research and implications for their business.

Practical implementable solutions – not just “over-clever analysis.”

Our knowledge is extensive and experience broad – please visit our website for a full listing of all our services.

Please don't hesitate to contact us for an informal discussion – either by telephone on +44 (0) 207 225 3538 or by email at: [email protected]


www.parioforma.com



mailto:[email protected]


the eu market for phase ii ib & iv studies

Health & Medicine

enforce european regulations

grey transition period

eu member state

european economic area

post marketing environment

late phase work

member state

accession countries