Re: Pharmaceutical research and development: what do we get for all that money?
Peter Høngaard Andersen, Chair, Research Directors Group (RDG), European Federation of Pharmaceutical Industries and Associations (EFPIA); H. Lundbeck A/S, Denmark.
Richard Bergström, Director General, EFPIA.
To the Editor,
We welcome open discussion of the current drug discovery and development process and its limitations, as raised by Light and Lexchin.(1) Although we do not propose to provide a detailed response to the individual postulates and numbers put forward by the authors, we would emphasise our surprise in their claim that it is possible to predict the true value of a medicine using the so-called ‘Norway model’.(2) This model is no longer in use in Norway, since such predictions have been shown to be unfeasible, and it is recognised that estimating the value of a medicine requires the documentation of real life use. However, we would like to discuss some of the points that were raised, especially with regard to current industry constraints and proposed revision of regulatory requirements, that we propose may accelerate and streamline the drug development and approval process.
We would agree that the authors are correct in stating that there is no “innovation crisis” – there is, however, a crisis in the cost of innovation. This is particularly relevant in terms of the high attrition rate of medicines in development, which often occurs late in the development process and after significant investment. The decline in R&D productivity in pharmaceuticals in the past two decades is “associated with an increasing concentration of R&D investments in areas in which the risk of failure is high, which correspond to unmet therapeutic needs and unexploited biological mechanisms”.(3) However, despite such high practical and financial losses, 49 new innovative medicines were approved during 2011 in the EU, covering several disease areas.(4) A total of 37 new non-orphan medicines, 11 orphan medicines and one advanced-therapy medicine were approved by the EMA (5), with ‘one third of drugs launched in 2011 [being] first in class’.(4) Among these new medicines was the first new treatment for lupus erythematosus for over fifty years.(6)
The authors imply that drug developers have too much control over clinical study design and that more stringent regulatory requirements for study design are required. In fact, the real issue is that the regulatory frameworks for the review and approval of new medicines, including already stringent study design requirements, have not evolved in step with technological advances in medical research. Patients, society and industry would all benefit from greater flexibility to allow more adaptive clinical trials, which are more efficient and better reflect the real-world patients who will benefit most from treatment.
A change is certainly needed to make the drug discovery and development process more productive, more efficient and more cost-effective for society. The pharmaceutical industry is aware of the issues highlighted by the authors and is committed to bringing about positive changes in the way truly innovative drugs are developed and approved. However, this is not achievable by the industry alone. Placing arbitrary restrictions on drug approval is not the answer – collaboration is what is needed. Investment in science has been consistent in the research based pharmaceutical industry, and progress comes in waves; witness the explosion of antivirals induced by the advent of HIV/AIDS, with zero applicable treatments at the beginning of the 1980s to over 25 agents specific to four separate viral processes at the present time. Such achievements have been gained by collaboration across academia and industry, and with support from government.
Current technological advances promise step-changes for patient care in Europe and beyond. ‘Personalised medicine’ allowing the tailoring of emerging therapies to individual patients or specific populations, via economically viable ‘omics’ examinations, is becoming a practical possibility. Effective data capture, essential to allow such a level of individualised treatment, will offer not only the repurposing of established medicines for new treatments, but also the prospect of reducing side effects in their established use. Biomarkers and diagnostics can be used to select patients more effectively for treatments and improve the efficiency of the clinical process, with the essential endorsement by regulators and funding from healthcare systems.(4)
The Innovative Medicines Initiative (IMI) is the world’s largest public-private partnership and aims to improve the drug discovery and development process through collaboration at all levels and steps of the pharmaceutical value chain in order to deliver better and safer medicines for the benefit of all stakeholders, including patients and society as a whole. The IMI is undertaking a range of projects with clearly defined, measurable outcomes to advance the understanding and classification of diseases, increase the efficiency of novel drug target validation and develop new, innovative methods to predict drug safety and assess clinical effects of new drugs. Additionally, new regulatory pathways will be investigated to inform discussion on regulatory guidance. The IMI will also develop novel therapeutic agents for areas with high unmet need but low return on investment. This highlights the role that the pharmaceutical industry is taking to develop medicines in areas that suffer from a lack of financial incentives but which offer a significant potential benefit to society.
Society is facing major health care challenges and industry is facing major challenges due to the costs of innovation. New innovative medicines addressing these challenges may not be secured by adding ever more restrictions and constraints on the industry. Only through collaboration between stakeholders, regulators, academia, payers and industry, as exemplified by the IMI, will the drug discovery and development process, and related regulatory frameworks, continue to evolve and ensure that these challenges are met, so that patients and society receive the best possible treatment options in the future.
We would like to thank the following for their counsel in preparing this response: Dr Ismail Kola (UCB); Dr Martin Mackay (AstraZeneca); Professor Trevor Jones (Allergan Inc.); Professor Mads Krogsgaard Thomsen (Novo Nordisk); and Dr Patrick Vallance (GlaxoSmithKline).
Rapid Response:
Re: Pharmaceutical research and development: what do we get for all that money?
Peter Høngaard Andersen, Chair, Research Directors Group (RDG), European Federation of Pharmaceutical Industries and Associations (EFPIA); H. Lundbeck A/S, Denmark.
Richard Bergström, Director General, EFPIA.
To the Editor,
We welcome open discussion of the current drug discovery and development process and its limitations, as raised by Light and Lexchin.(1) Although we do not propose to provide a detailed response to the individual postulates and numbers put forward by the authors, we would emphasise our surprise in their claim that it is possible to predict the true value of a medicine using the so-called ‘Norway model’.(2) This model is no longer in use in Norway, since such predictions have been shown to be unfeasible, and it is recognised that estimating the value of a medicine requires the documentation of real life use. However, we would like to discuss some of the points that were raised, especially with regard to current industry constraints and proposed revision of regulatory requirements, that we propose may accelerate and streamline the drug development and approval process.
We would agree that the authors are correct in stating that there is no “innovation crisis” – there is, however, a crisis in the cost of innovation. This is particularly relevant in terms of the high attrition rate of medicines in development, which often occurs late in the development process and after significant investment. The decline in R&D productivity in pharmaceuticals in the past two decades is “associated with an increasing concentration of R&D investments in areas in which the risk of failure is high, which correspond to unmet therapeutic needs and unexploited biological mechanisms”.(3) However, despite such high practical and financial losses, 49 new innovative medicines were approved during 2011 in the EU, covering several disease areas.(4) A total of 37 new non-orphan medicines, 11 orphan medicines and one advanced-therapy medicine were approved by the EMA (5), with ‘one third of drugs launched in 2011 [being] first in class’.(4) Among these new medicines was the first new treatment for lupus erythematosus for over fifty years.(6)
The authors imply that drug developers have too much control over clinical study design and that more stringent regulatory requirements for study design are required. In fact, the real issue is that the regulatory frameworks for the review and approval of new medicines, including already stringent study design requirements, have not evolved in step with technological advances in medical research. Patients, society and industry would all benefit from greater flexibility to allow more adaptive clinical trials, which are more efficient and better reflect the real-world patients who will benefit most from treatment.
A change is certainly needed to make the drug discovery and development process more productive, more efficient and more cost-effective for society. The pharmaceutical industry is aware of the issues highlighted by the authors and is committed to bringing about positive changes in the way truly innovative drugs are developed and approved. However, this is not achievable by the industry alone. Placing arbitrary restrictions on drug approval is not the answer – collaboration is what is needed. Investment in science has been consistent in the research based pharmaceutical industry, and progress comes in waves; witness the explosion of antivirals induced by the advent of HIV/AIDS, with zero applicable treatments at the beginning of the 1980s to over 25 agents specific to four separate viral processes at the present time. Such achievements have been gained by collaboration across academia and industry, and with support from government.
Current technological advances promise step-changes for patient care in Europe and beyond. ‘Personalised medicine’ allowing the tailoring of emerging therapies to individual patients or specific populations, via economically viable ‘omics’ examinations, is becoming a practical possibility. Effective data capture, essential to allow such a level of individualised treatment, will offer not only the repurposing of established medicines for new treatments, but also the prospect of reducing side effects in their established use. Biomarkers and diagnostics can be used to select patients more effectively for treatments and improve the efficiency of the clinical process, with the essential endorsement by regulators and funding from healthcare systems.(4)
The Innovative Medicines Initiative (IMI) is the world’s largest public-private partnership and aims to improve the drug discovery and development process through collaboration at all levels and steps of the pharmaceutical value chain in order to deliver better and safer medicines for the benefit of all stakeholders, including patients and society as a whole. The IMI is undertaking a range of projects with clearly defined, measurable outcomes to advance the understanding and classification of diseases, increase the efficiency of novel drug target validation and develop new, innovative methods to predict drug safety and assess clinical effects of new drugs. Additionally, new regulatory pathways will be investigated to inform discussion on regulatory guidance. The IMI will also develop novel therapeutic agents for areas with high unmet need but low return on investment. This highlights the role that the pharmaceutical industry is taking to develop medicines in areas that suffer from a lack of financial incentives but which offer a significant potential benefit to society.
Society is facing major health care challenges and industry is facing major challenges due to the costs of innovation. New innovative medicines addressing these challenges may not be secured by adding ever more restrictions and constraints on the industry. Only through collaboration between stakeholders, regulators, academia, payers and industry, as exemplified by the IMI, will the drug discovery and development process, and related regulatory frameworks, continue to evolve and ensure that these challenges are met, so that patients and society receive the best possible treatment options in the future.
References
(1) Light DW, Lexchin JR. Pharmaceutical research and development: what do we get for all that money? BMJ 2012; 345:e4348.
(2) Joldal B. Regulation for need - the Norwegian experience. Journal of Social and Administrative Pharmacy 1984; 2:81-84.
(3) Pammolli F, Magazzini L, Riccaboni M. The productivity crisis in pharmaceutical R&D. Nat Rev Drug Discov 2011; 10(6):428-438.
(4) EFPIA Annual Review of 2011 and Outlook for 2012, www.efpia-annualreview.eu/uploads/efpia.pdf
(5) EMA Monthly statistics report Dec 2011, www.ema.europa.eu/docs/en_GB/document_library/Report/2012/02/WC500123265...
(6)EMA Benlysta (belimumab), EPAR summary for the public, www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_pub...
We would like to thank the following for their counsel in preparing this response: Dr Ismail Kola (UCB); Dr Martin Mackay (AstraZeneca); Professor Trevor Jones (Allergan Inc.); Professor Mads Krogsgaard Thomsen (Novo Nordisk); and Dr Patrick Vallance (GlaxoSmithKline).
Competing interests: No competing interests