All posts by ilsintelligence

Guess who invented the Target Product Profiles…

By Itziar Escudero, Ph.D., M.B.A. Partner at Insights in Life Sciences (ilS).

A Target Product Profile (TPP) is a planning tool for therapeutic candidates based on FDA guidelines.

The TPP defines the minimal and ideal profile of the final marketed product and shows the ultimate goals of the proposed therapy development effort such as disease indication, patient population, delivery mode, treatment duration, treatment regimen, and standards for clinical efficacy.

Target-product-profile-template (1)

Fig1. Standard TPP (you can download a template here)

The TPP concept was used for the first time more than 20 years ago (in 1997), when FDA representatives and pharmaceutical sponsors were looking for ways to improve sponsor and FDA interactions during the drug development process.

The purpose of a TPP is to provide a format for discussions between a sponsor and the FDA that can be used throughout the drug development process, from pre-investigational new drug application (pre-IND) or investigational new drug application (IND) phases of drug development through postmarketing programs to pursue new indications.

The TPP embodies the notion of beginning with the goal in mind. That is, the sponsor specifies the labeling concepts that are the goals of the drug development program, documents the specific studies intended to support the labeling concepts, and then uses the TPP to assist in a constructive dialogue with the FDA.

The use of the TPP has evolved and nowadays does not only facilitate the dialogue between the sponsor and the FDA, but with other stakeholders (such as physicians and payers) as well.

In fact, at ilS we help Companies assess how those stakeholders (physicians and payers) “react” to the different TPP presented, including the minimally acceptable and the desired scenarios. For this purpose we count with a network of life sciences experts (ilS NetworkSM) from all over the world, including physicians and payers, with whom we conduct in-depth phone interviews and collect their perspective around the TPP.

Ideally, the TPP provides a statement of the overall intent of the drug development program, and gives information about the drug at a particular time in development. Usually, the TPP is organized according to the key sections in the drug labeling and links drug development activities to specific concepts intended for inclusion in the drug labeling.

The TPP is a dynamic summary that changes as knowledge of the drug increases. For optimal use, it is recommended to update regularly the TPP to reflect new information about the product.

Early TPPs can be brief depending on the status of the sponsor’s development process.

A well-organized TPP is also useful for updating quickly sponsor personnel who join the program for the first time.

The is part of the proprietary IND file. Nevertheless, a TPP does not represent an implicit or explicit obligation on the sponsor’s part to pursue all stated goals.

According to the FDA, sponsors have seen advantages of using a TPP at meetings early in the drug development process. Use of a TPP can facilitate the efficiency of sponsor-FDA interactions and communications. A TPP can help address issues early on in the drug development process thereby preventing late stage drug development failures and decreasing the total time involved with drug development.

In the same way, we at ilS, have seen advantages of using TPPs for Companies (sponsors) that seek stakeholder input. This tool allows physicians and payers to comment on the product profile in an organized manner and to evaluate different scenarios. We have observed that this tool is useful not only in later stages of drug development, but also in early stages where there is still so much room for change for the sponsors.

Interestingly enough, we have also found this tool useful for evaluating in vitro diagnostics (IVD) devices, adjusting the TPP template.

References:

https://www.ninds.nih.gov/Funding/Apply-Funding/Application-Support-Library/CREATE-Bio-Example-Target-Product-Profile-TPP

https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm080593.pdf.

The CBER Office of Cellular, Tissue and Gene Therapies (OCTGT) web page for industry education also has a Webinar on TPP

 

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How Primary Research Helps Companies Succeed?

By Angela Justamante, M.S., Consultant at Insights in Life Sciences (ilS).

Market Research is an organized effort to gather information about target markets or customers. It is a very important component of business strategy. Market Research is one of the key factors used in maintaining competitiveness over competitors, providing important information to identify and analyse the market need, market size and competition. Market Research techniques encompass both primary and secondary market research. 1

Whereas secondary research, also known as desk research, involves the summary, collation and/or synthesis of existing research, primary research involves the collection of data directly from the source of knowledge (physicians, patients, payers, Company representatives,…).

Primary research is generally conducted by third parties, in order to maintain as much objectivity as possible. Those providers should ideally be familiar with the Efpia code of practice (which recommends how organization should interact with healthcare professionals and patient organizations) . 3 Data collected through primary research is interpreted using statistical or analytical methods and techniques to gain insights and support decision making.

Primary market research can be made through qualitative techniques such as in-depth one to one interviews or quantitative techniques such as questionnaires. 2

The following case studies, allows to gain a better understanding of how primary research can support companies’ decision-making.

Case study: NIVEA deodorant “Pearl and Beauty”

Beiersdorf is a big German personal-care company based in Hamburg, Germany, that includes brands such as: NIVEA, Eucerin and Atrixo. One of the main reasons of Beiersdorf’s success is the in-depth market research they conduct (in a global context). The aim of this market research is to gather end user views, which provides insights that ultimately result in the development of new products suitable for a global market.

A clear picture of how market research has helped New Product Development (NPD) at Beiersdorf, is the case of a NIVEA Deodorant called Pearl and Beauty aimed at young women.

The objective of this primary market research was to understand the motivations for using deodorant amongst female consumers. The research involved small discussion groups of females, which helped researchers understand the beliefs and motivations of this group and revealed an interesting finding: apparently NIVEA lacked a specific product that addressed ‘underarm beauty’ for the female consumer.

As a result, this primary market research revealed an unexplored market potential for NIVEA Deodorant. And, in order to fulfil this market need, NIVEA successfully launched to the market a Deodorant called Pearl and Beauty 4

Insights in Life Science (ilS) has successfully conducted primary research studies for a variety of life sciences companies, including: big pharma, biotech, start-ups, Tech Transfer Offices,  or even for other consulting organizations

We share three case studies below (slightly modified for confidentiality purposes), which try to illustrate how primary research adds value to our Clients:

Case Study 1:

A start-up biotech company focused in the field of neurology and ready to initiate a Phase II Proof-of-Concept for one of its products, was interested in understanding Key Opinion Leader (KOL) and payer perception of that product (“Product X”). For that purpose, ilS selected the best potential neurologists and payers (across the top 5 EU countries and the USA), prepared an exhaustive interview guide and held in-depth phone interviews with those experts (ilS InterviewsSM)

Insights collected through this primary research allowed our Client to understand expert perception of its Target Product Profile (TPP), and potential Market Access barriers. Those first-hand insights allow the Company to: 1. Revisit the Product Development Plan in an early stage, 2. Be better prepared to negotiate with licensors, 3. Attract investor attention during a potential fund raising phase

Case Study 2:

The Office of Technology Transfer of a Nordic University developing a new treatment in the field of Ophthalmology (“Product Y”), was interested in understanding end user clinical practice, existing unmet clinical needs, and market potential for “Product Y”. For that purpose, ilS conducted a primary research (ilS SurveysSM) with top ophthalmologists across the USA and the top 5 EU countries. With the support of the ilS NetworkSM, ilS identified the best KOLs, prepared an exhaustive online survey and collected expert insights. ilS analyzed the compiled information and shared a report with the Company allowing them to: 1. Decide whether or not to continue further developing “Product Y”, 2. Understand the potential market size for a rare ophthalmologic condition

Case Study 3:

A Global Pharma Company in preparation for the market launch of “Product Z”, needed to gain insights from several qualified oncologists in regards to their decision-making process, their product perception and values. For this purpose, ilS organised an onsite Advisory Board with several oncologists in order to capture their insights and gain consensus (ilS KnowledgeSM). More specifically, ilS created a well-designed moderator guide based on the client provided information, conducted the advisory board, collected the expert insights, analyzed the compiled information and shared a report. The Advisory Board provided sufficient insights to develop an optimal local strategy that could facilitate a smoother launch for “Product Z”

Those three case studies, illustrate how primary research supports life sciences companies to gather key data directly from the target customers, and adds value in regards to: target product profiling, clinical trial design, early market access plan, pricing strategy, licensing strategy, fund raising,…, which allow organizations to become more efficient and accelerate new product launch, which in the end will benefit patient health, which is what really matters.

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REFERENCES

  1. McQuarrie, Edward (2005), The market research toolbox: a concise guide for beginners (2nd ed.), SAGE, ISBN 978-1-4129-1319-5
  2. Wikipedia (https://en.wikipedia.org/wiki/Secondary_research)
  3. Efpia Relationships & Codes: https://www.efpia.eu/relationships-codes/
  4. NIVEA- Case Study, International Market Research (http://bit.ly/2Dk8POh)

Risk Sharing Agreements: Friends or Foes?

By Itziar Escudero, Ph.D., M.B.A. Partner at Insights in Life Sciences (ilS).

In risk sharing agreements, particularly health outcomes-based agreements, the price and reimbursement of a new drug is associated with the achievement of certain health outcomes in real-world practice. Health outcomes can be measured in terms of clinical results (through intermediate or final indicators) or of cost-effectiveness (through estimation of the incremental cost-effectiveness ratio).

According to the nature of reimbursement, health outcomes-based agreements can be classified into: conditional coverage and performance-linked reimbursement (or pay for performance). Conditional coverage agreements may provide patients access to new drugs while data to provide definitive evidence for the clinical or cost effectiveness impact are collected. On the other hand, performance-linked reimbursement (pay for performance) agreements are usually negotiated when the manufacturer is very confident in its product and the value it creates so it is willing to accept a lower reimbursement if the drug fails to achieve the expected health outcomes in real-life.

Health outcomes based agreements are not recommended for drugs whose health outcomes can only be evaluated after a long period of time and for drugs for which no specific and reliable outcome measurements can be defined. Their introduction can be complicated due to the variety of arrangements possible, they may require the transfer of patient data (with implications for confidentiality). Additionally, outcomes- based agreements may have high implementation, administrative, and monitoring costs and negotiations involved can be very time-consuming.

In the Spanish National Health System (NHS, SNS in Spanish), the implementation of these agreements may result in additional issues, in particular related to the decentralization in the decision-making process at the regional and hospital level (taking into consideration the 17 Autonomous Regions in Spain). This could raise questions regarding who (central government, regional health services or hospitals) should negotiate, manage and fund these agreements.

Another issue that must be taken into consideration is the fact that, in general, knowledge in these type of arrangements is extremely limited and both hospital and regional health services lack the appropriate personnel. Moreover, challenges linked to the absence of legal regulation of this form of agreements at European and national level must be addressed.

According to Dr Miguel Ángel Calleja, Head of Pharmacy at Virgen de las Nieves Hospital and President of the Spanish Society of Hospital Pharmacy (SEFH), “One of the problems related to the implementation of risk-sharing agreements in Spain is the lack of awareness among professionals and the inadequate monitoring of treatments”.

Nevertheless, the severe financial downturn Spain is facing is sparking interest in health outcomes based agreements, particularly at the regional and hospital level although with varying degrees of implementation across the different Autonomous Regions, with Catalonia leading the way in number of agreements and drugs involved.

For example, at the national level, within the Strategic Plan of the Spanish Government to address hepatitis C, the Ministry of Health has signed a combination of risk-sharing agreements with different pharmaceuticals companies to provide access to the new drugs for the treatment of hepatitis C. The Ministry has signed with MSD for the purchase of Victriles® (boceprevir) an agreement based on the concept of “cured patient”, so the SNS will pay only for these patients, while MSD will finance the cost of patients who do not reach the agreed viral load.

At the hospital level the first Performance Based Agreement entered in Spain was another outcomes-guarantees done between the Hospital Virgen de las Nieves in Granada and GlaxoSmithKline in 2012 for the purchase of Volibris® (ambrisentan) for the treatment of idiopathic pulmonary hypertension (PAH). In this case a technical committee (composed of a doctor, a GlaxoSmithKline representative, the hospital manager, a representative from the hospital pharmacy department, and a representative from the Andalusian School of Public Health) was responsible for monitoring the functioning of the agreement.

A linear model of payment was agreed so that the amount the Hospital pays depends on the performance of the drug with respect to previously established outcomes. Even though the treatment does not work as expected, under this arrangement the manufacturer receives a part of the payment. The annual cost of implementing this agreement was approximately 1% of the annual cost of the drug, being data collection the most costly aspect of the implementation.

Furthermore, at the regional level, the implementation of performance-based risk-sharing agreements is included in the 2011-2015 Health Plan for Catalonia. One of the goals of this Plan is to enter into ten risk-sharing agreements with pharmaceuticals companies by 2015. CatSalut, the Catalonia Health Service, intends to continue working on this type of agreements and to move toward an innovation and performance-based model of funding.

However, it is yet to be seen if the rest of Autonomous Regions will follow Catalonia’s example, potentially allowing further patients living in other regions gaining access to important treatments in the future (as a result of the implementation of risk sharing agreements).

When asked about the implementation of risk sharing agreements in Spain, during a breakfast organized by ilS, experts agreed that although the implementation of these agreements can be difficult, they are highly necessary nowadays. For Dr. Antoni Gilabert, Managing Director of Pharmacy and Medicines at Servei Català de la Salut (CatSalut), these agreements must be adopted to minimize uncertainty and to establish a win-win situation for both pharma companies and payers. Additionally, Dr. Gilabert believes that for successful implementation of risk sharing agreements, stakeholders must have a well-defined set of outcome indicators and a well-established monitoring methodology.

For Ms. Mercedes Prior, Head of Global Market Access at Almirall, risk sharing agreements allow and accelerate access to new drugs that otherwise would not make it to the market. Nevertheless, Ms. Prior acknowledges the hurdles related to the implementation of these agreements, given that many of the different departments within a pharmaceutical company (like; market access, medical affairs, legal, finance …) must be aligned.

Overall, risk sharing agreements provide a stable framework to finance innovation. Due to the fact that they are dependent on health outcomes, they encourage the effectiveness of products and enhance their post marketing research. However, the implementation of risk sharing agreements is complex, time-consuming, and an expensive process. Particularly the decentralized structure of the Spanish health system further elevates this complexity, increasing the stakeholders involved in the pricing and reimbursement process of a new drug.

ilS PublicationsSM latest report “Market Access and Innovative Agreements in Spain” speaks about the different types of innovative agreements that pharma companies can implement (including risk sharing agreements). Additionally, it describes in an easy-to-read manner the Spanish healthcare system, clarifies the process of introducing a new drug in Spain, and provides information about the roles different stakeholders play at a national, regional and local levels, as well as the different levels of influence they exert. All of that allow decision makers from biopharmaceutical companies to set-up the right new drug launch strategy that will guarantee an optimal access into the Spanish market.

Click here to download your copy of ilS PublicationsSM latest report “Market Access and Innovative Agreements in Spain”

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ilS Speaker Series(SM): 2nd Edition Highlights on Orphan Drugs and their Access to Patients

By Anna Reyes, MSc, Consultant at Insights in Life Sciences (ilS).

ilS Speaker Series 2015The Second Edition of ilS Speaker SeriesSM titled “Orphan Drugs: How to Accelerate their Access to People Who Suffer from Rare Diseases?” was celebrated last Friday, March 27th, at the Rafael del Pino Auditorium in Madrid. Similarly to the First Edition, the event counted with the participation of industry representatives, health authorities, leading physicians and researchers and members from patients’ associations.

In the opening, Dr. Regina Revilla (President of the Spanish Association of Bio-Companies, ASEBIO) highlighted both the importance and impact of the Rare Diseases for the public National Health System (NHS) and made a call to all the health agents to commit themselves in collaborative efforts with patients. In the current situation, “rare diseases must be a priority in health policies”, Dr. Revilla said. Right after, Mr. Juan Carrión (President of the Spanish Federation of Rare Diseases, FEDER) stressed that the access to Orphan Drugs remains one of the biggest worries for patients. In his own words, “accelerating the access of orphan drugs means improving patients’ quality of life”, so it should be first priority for governments to do so without inequalities between regions.

Dr. Itziar Escudero, partner at ilS, gave a brief overview on rare diseases and shared some interesting numbers with the audience. A rare disease affects less than 5 out of 10,000 individuals. The 80% of cases are of genetic origin and they affect 3 million people in Spain. Although 6,000 to 8,000 rare diseases exist, medical and scientific knowledge is available only for the 30% of them. In Spain, the NHS finances 45 out of the 62 European Medicine Agency (EMA) approved orphan drugs and this year 1.7 M€ will be destined to the Strategy in Rare Diseases.

As Mr. Carrión, Mr. Justo Herranz, member of the Advisory Board of FEDER, pointed out the administrative issues, the unmet needs regarding access and the inequities across regions that Orphan Drugs are facing. The vast majority of rare diseases are chronic, disabling and have late diagnosis. A 27% of patients have received an inadequate treatment while a 30% suffer disease progression by the time diagnosis is revealed. The health system decentralization in Spain is detrimental to all patients suffering from Rare Diseases, given that assessment criteria for Orphan Drugs are strict and mandatory at regional and hospital level. Drug expenditure is the driving force for decision making regarding reimbursement and some penalties have been applied to health centers whose drug expenditure has exceeded budget. Mr. Herranz told the audience “this type of reality does not, by any means, give answers to the severe needs of patients”. FEDER is fighting for the establishment of Center Services of National Reference (CSUR), centers where patients coming from any region can be assisted accordingly (in-site or online) by the best specialists. The reality so far though, is that many centers are still unwilling to set up a CSUR for economic reasons and many hospitals are still opposed to the creation of clinical registers for Rare Diseases. However, Mr. Herranz was determined: “we can’t let ourselves the luxury of falling into hopelessness”.

The round table revealed an interesting, open and vibrant discussion about all the key aspects about the access to Orphan Drugs. From the R&D side, Dr. Palau highlighted that during 2009-2014, 328 R&D Spanish projects funded by the Health Institute Carlos III (ISCIII) and some other public grants have been carried out in the field of Rare Diseases. Although the current economic situation has forced the reduction of many of the resources, Spanish research is still out there and it is bearing its fruits. Some clinical trials are already ongoing for Orphan Drugs, as well as some studies for drug screening and gene or cellular therapy. Scientists are particularly interested in unveiling the genetic origin of these diseases and for that reason, 352 genes are under study. Besides, there are European Reference Networks (ERNs) for Rare Diseases and Spain will be taking part of them through CSUR centers, publicly financed by the government.

Dr. Blázquez indicated that European regulations in the field of Orphan Drugs count 15 years now and that the balance of the whole period has been positive: more than 1,400 drugs have obtained the Orphan Designation. Last year 15 new Orphan Drugs were approved and, currently, 27 are being evaluated. Moreover, at regulatory level, Orphan Drugs could benefit from market exclusivity, help in protocol elaboration, reduction of taxes to the European Medicines Agency (EMA) and support in R&D. It is important to mention that, in recent years, patients’ have gained their spot in regulatory commissions in Europe, while in Spain they are not a relevant stakeholder. Besides, Spain is standing up for the compassionate use when there is a clinical request from doctors, then some Orphan Drugs may be in clinical use for 4 or 5 months before regulatory approval.

Mr. Sánchez-Fierro stated that “there are elements of hope, but also elements of concern”. Barriers have lowered at European level, whereas Spanish internal barriers have somewhat strengthened. In Spain, drug assessments are conducted by a number of institutions (Spanish Agency of Medicines and Sanitary Products (AEMPS), health departments from autonomous communities, local hospitals, etc.) which, eventually, call patients’ rights into question from a practical point of view. Similarly, a Cohesion Fund once created is now kind of dissolving by many other funds that break the system’s wholeness. At this point, it is important to put ethics over economics and try to find the way out through objective and harmonized criteria across regions. Mr. Sánchez-Fierro also indicated that “ethics must be applied as well in clinical trials and compassionate uses by means of informed consent”. Patients must be always, at any point, informed about every action and risk being taken on them and the possibility of retracting in a language they can easily understand.

“Price negotiations within industry and Ministry of Health are public debates. Industries always pursue, as a priority, the return of the R&D investment as well as the company’s viability”, Mrs. Serrano explained. Only 3 out of 10 drugs cover R&D expenses. Additionally, in the field of Orphan Drugs, prevalence is really low so drug prices must be higher versus other drugs to return investment. Notably, the investment needed to develop an Orphan Drug exceeds the 1,200 M€ and many years of hard work on average; nevertheless, the return, if achieved, is only around 5-10%.

Ministry of Health’s price and reimbursement criteria for Orphan Drugs are the same as for the rest of innovative drugs. Among the most important criteria for drug reimbursement, we may find degree of innovation and therapeutic value of the drug, severity, duration and negative effects of the disease, cost-effectiveness and budget impact for the NHS. “Cost-effectiveness and budget impact criteria trigger all the issues this type of drugs present”, said Mrs. Martínez. Still, Orphan Drugs are reimbursed based on the answer they give to other important criteria such as severity and consequences of Rare Diseases, together with the huge impact they have on patients. At regional level, the cost of these products is really high due to the exclusivity of the Orphan Drug, which lowers the price flexibility, limiting payer’s options. There are no specific funds for Orphan Drugs currently in Spain. Although Orphan Drugs’ national reimbursement in Spain is remarkably high (80-90%), hospital managers handle budgets destined to cover all hospital treatments, not only Rare Diseases treatments. They have the last word regarding those decisions affecting the hospital’s budget overall and pharmacoeconomics plays an important role.

During the Q&A with the public, the role of hospital managers was brought up to discussion again. In conclusion, all contributions pointed that the responsibility for the access should be taken by the government, instead of health personnel. A single system without barriers between regions, for instance based in the recent national Therapeutical Positioning Reports (IPT), could help to avoid such drugs’ reassessments at regional or local levels and to lower hospitals’ budgetary pressure. In addition, strategies between biopharmaceutical companies and payers were proposed to accelerate Orphan Drugs’ accessibility to patients. These state alliances, defended by speakers and audience including Dr. Muñoz (Ex-President and Founder of Superior Council of Scientific investigations (CSIC)), might take place in the form of regulated pay per performance agreements, expenditure ceiling agreements, maximum expense per patient agreements or maximum global expense agreements. Because Rare Diseases are not only a pharmacoeconomic concern but a social and therapeutic one too, social responsibility from all health agents is needed in order to improve the current dynamics and eventually achieve a good equilibrium for all parts towards the future. Finally, speakers agreed on the need of an epigraph for Rare Diseases within the National Cohesion Fund of the Ministry of Health.

 

The impact of Rare Diseases in Spain

By Anna Reyes, MSc, Consultant at Insights in Life Sciences (ilS).

Rare Disease DayA Rare Disease is a disease which affects a limited number of the total population, defined in Europe as less than 5 in 10,000 citizens.1 The origin, in nearly eight out of ten cases, is genetic and they affect both children and grown-ups.2 In case the disease affects less than 1 in 50,000 people, we would be referring to it as an Ultra-Rare Disease.3

Globally, it is estimated that between 6,000 and 8,000 Rare Diseases exist.2 However, minimal medical and scientific knowledge is just available for the 30% of them.3

A 6 to 8% of the worldwide population is affected by such diseases, which translates into more than 3 million Spanish people, 27 million of Europeans and 25 million of North-Americans.3 If we estimate an average of 4 people per family, in Spain there are about 12 million people who daily live with a Rare Disease, either for directly suffering from them or for being closely related to a person who does.4

About 50 Rare Diseases affect several thousands of people in Spain, about 500 affect no more than a few hundreds and few thousands apply hardly to tens of people. Specifically in Spain, the Federación Española de Enfermedades Raras (FEDER)5 indicates that the five most common affections within the group of Rare Diseases are:

  • Hemoglobinopathies (mainly Thalassemia and Drepanocitosis): They affect around 10,000 Spanish people. They are diseases which affect the survival or formation of the erythrocyte, altering the oxygen transport.1,2 Drepanocitosis can be treated with simple measures: plenty of liquid intake, healthy diet, folic acid supplements, analgesics, vaccines and antibiotics for preventing and treating infections. A severe thalassemia requires periodic blood transfusions. Multiple transfusions produce an iron over-load in several organs, alteration which also needs treatment. Thalassemias can be cured by means of bone marrow transplants, but these remain an expensive intervention that is not easily available in the vast majority of centers. Recently, gene therapy has succeeded in a patient with thalassemia.6
  • Amyotrophic Lateral Sclerosis (ELA): It affects 6,000 Spanish people. It is a disease in which nervous cells get damaged or die, being unable to send messages to the muscles and leading to a final state of muscular debilitation and inability to move either the body or the limbs.8 The cure is still unknown. A drug named Riluzole helps to delay the symptoms, allowing the patients to live longer. Other measures of treatment would include the use of medications to control the spasticity, anticholinergics for those patients who present problems to shallow their own saliva, gavages to facilitate feeding, constant mechanical ventilation to breathe, physiotherapy and rehabilitation.8
  • Scleroderma: It affects 5,000 Spanish people. The disease makes the connective tissue turn stiff and thick. It can also cause inflammation or pain in the muscles and articulations. Some types can affect the skin, making it stiff and tense. Other types affect the blood vessels and main organs such as the heart, lungs and kidneys.9 The disease has no cure yet, but its symptoms and caused damages can be diminished by vasodilators, analgesics, antiinflammatories, exercise for articulations, frequent use of sun screen, permanent oral hygiene, constant hydration, medication for intestinal regulation and antihypertensives9.
  • Cystic Fibrosis: Affects between 4,000 and 5,000 Spanish people. It is a degenerative disease which affects mainly the lungs and the digestive system. Nowadays, the pathology has no cure. The treatment is based on getting an adequate nutrition, using drugs which fight against the respiratory inflammations and infections and doing respiratory physiotherapy exercises, exercises to strengthen the muscles of the thorax to prevent deformities and some sport. When the disease reaches an advanced stage, the possibility of performing a pulmonary and/or hepatic transplant exists.10
  • Duchenne Muscular Dystrophy (DMD): Affects 3,000 Spanish people. It is a progressive disorder of the muscles that causes their function loss and thus, all those affected end up losing their independence. This progressive muscle feebleness leads to serious medical problems. Affected children need a wheelchair when they are barely 12 and the average life expectancy is 30 years.11 Although there is not a cure yet, some accepted treatments exist. These reduce the symptoms and improve quality of life: corticosteroids administration, adequate feeding, hydrotherapy, physiotherapy exercises and periodic evaluation of the muscular, respiratory and cardiac functions.11

In terms of expenditure, the direct economic impact of these diseases is high. At domestic level, the cost of the treatment for such an infrequent disease ranges from 500 to 700 euros per family per month.12 An epidemiologic observational study in 2012, with 593 Spanish patients suffering from 8 types of different Rare Diseases, determined that the greater cost of the families facing these diseases was informal care (care of the affected person) in the first place, followed in importance by the costs related to medical visits and drugs, respectively.13 At health system level, the cost is also really high, given that the investment needed to develop an Orphan Drug usually exceeds the 1,000 million euros and 12 years of work from the synthesis of the potential drug until its commercialization. Additionally, it has to be taken in mind that only 1 out of 100,000 investigated molecules reach commercialization in order to be available for those patients in need.3

The indirect economic impact is also highly relevant for those pathologies. The great majority of those patients affected require a certification of disability, which prevent them from working and therefore, from generating income and paying contributions to the National Health System. In the same way, caregivers also see their work and incomes compromised by the situation.

The current model of public funding for Orphan Drugs in Spain is a decentralized management model where the authorization decisions correspond to the Spanish Medicines and Sanitary Products Agency (AEMPS) and funding decisions fall on the Ministry of Health, Social Services and Equality (MSSSI). After the authorization and the funding, the price is fixed by the Interministerial Price Commission for Medicines (CIPM) and the Orphan Drug is put at health services’ disposal in the different autonomous communities, assuming each one of them has the responsibility of management and rational use.14

In Europe, the European Medicines Agency (EMA) has authorized 85 Orphan Drugs. In Spain, the AEMPS has authorized 69 of those active ingredients. However, only 47 products have been granted price and reimbursement and are currently marketed; the 22 remaining drugs are still pending the reimbursement decision by the CIPM. 15

Presently, those affected by a Rare Disease wait an average of 5 years in order to be correctly diagnosed, reaching the 10 years in 20% of the cases. This fact implies a series of negative and irreversible consequences in the majority of cases, which could have been avoided in addition to the disease worsening in 30% of the patients. Until this date, FEDER has registered more than 3,160 consultations of affected people without diagnostic.2 Among the causes for diagnostic delay, we find lack of adequate diagnostic tests, lack of coordination among professionals of primary and specialized attention and the barriers among autonomous communities in the case of Spain.

In order to solve this problem, FEDER is willing to start a program aimed at those people who are in doubt of suffering a Rare Disease and have no diagnosis yet. The objective is to create specialized laboratories across locations, where patients could go and run all the necessary tests required to diagnose or study the pathology. The offered services would include clinical testing, second medical opinion, genetic testing and neonatal screening, among others.16

ilS has decided to focus the Second Edition of its ilS Speaker SeriesSM  (March 27th in Madrid, Spain) on this subject with a presentation entitled: “Orphan Drugs: How to Speed Up their Access to Patients with rare diseases?”.
See the agenda and register to the event: www.ilsintelligence.com/ils-speaker-series

 

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1 Website European Commission. EC Regulation on Orphan Medicinal Products http://bit.ly/1Elvl4w (04/03/15)
2 El País 17/02/2015 http://bit.ly/1vVfpoA
3 Webconsultas 04/03/2015 http://bit.ly/1B70F4Y (04/03/15)
4 Website Centro de Referencia Estatal de Atención a Personas con Enfermedades Raras y sus Familias de Burgos (Creer) http://bit.ly/1DNMBMk (04/03/15)
5 Website Federación Española de Enfermedades Raras http://bit.ly/1C3HlIJ (04/03/15)
6 Website Asociación Hemoglobinuria Paroxística Nocturna http://bit.ly/1zJTICV (04/03/15)
7 Website Organización Mundial de la Salud http://bit.ly/1zYnlBN (04/03/15)
8 Website Medline Plus http://1.usa.gov/1iA006l (04/03/15)
9 Website Instituto Nacional de Artritis y Enfermedades Musculoesqueléticas y de la Piel http://1.usa.gov/1AJheQO (04/03/15)
10 Website Federación Española de Fibrosis Quística http://bit.ly/1sAyNCf (04/03/15)
11 Website Asociación Duchenne Parent Project España http://bit.ly/1wIawj7 (04/03/15)12 Gaceta Médica 31/10/2013 http://bit.ly/1zYnsgv
12 Gaceta Médica 31/10/2013 http://bit.ly/1zYnsgv
13 Los costes socioeconómicos y la calidad de vida relacionada con la salud en pacientes con enfermedades raras en España. Proyecto de IMSERSO Nº 167/10 http://bit.ly/1B1FzGh
14 Nuevos modelos de financiación pública en medicamentos huérfanos. Mercedes Martínez Vallejo. bit.ly/1M5OfNF
15 El Global 23/02/2015 http://bit.ly/1aLxiwo
16 Lainformacion.com 20/02/2015 http://bit.ly/1F9XDxH

Consensus building: The Delphi Method and the Nominal Group Technique

By Aina Pi, M.A., Consultant at Insights in Life Sciences (ilS).

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Two of the best known methodologies to achieve consensus of opinion in expert panels or workshops are the Delphi Method and the Nominal Group Technique.

Both consensus techniques, widely used in the field of health, are a mean of collecting experts’ opinions where limited or conflicting evidence exists, and an approach of guiding health decision-making.

In practice, the Delphi method and the nominal group technique are frequently implemented to reach agreement on the classification of diagnostic criteria, the development of clinical guidelines, the identification of health professionals’ needs, as well as to orientate research.

The methodological manual for the development of Clinical Practices guidelines of the Spanish Ministry of Health1 states that these methods are particularly useful specifically if a general agreement on the formulation of recommendations is required: when there is a lack of scientific evidence, existing evidence is disputed, or when there is a little risk-benefit balance.

The Delphi method and the nominal group technique are described below:

Delphi method:

  • A Delphi study works as follow: An open-ended questionnaire about a particular topic is shared for an initial round of independent opinions from isolated respondents. The full range of opinions are summarized and distributed for several rounds of independent opinion and ranking, until a high degree of consensus is reached. Delphi studies usually consist of three to five rounds.
  • The Delphi method minimizes the influence of individuals and maximizes the reliability of results
  • The anonymity of the procedure allows to easily raise controversial issues
  • Since the exchange of information takes place via written documentation, no interactive discussion occurs. Nevertheless, the Delphi method can be adjusted for face-to-face meetings. In this regard, we have developed a “Delphi-like” methodology at ilS that counts with previous Interviews or Surveys, followed by Expert panels, known as ilS Knowledge(SM).
  • The Delphi method is very useful for international research since there is no need to gather all experts in the same location
  • The Delphi method requires an exhaustive prepared questionnaire, adequate time and high participant motivation since it involves a considerable workload for participants

The following case study, allows to gain a better understanding of how the Delphi method works:

Case study: Rationales behind the choice of administration form with fentanyl: Delphi survey among Danish general practitioners (GPs)2

  • The objective was to describe the rationale behind the choice of fentanyl (often used in the management of chronic pain) administration forms among Danish GPs.
  • An expert panel of 33 GPs collaborated in the study. In the first round, they wrote the main reasons for prescribing and not prescribing fentanyl patches, oral transmucosal systems, and nasal sprays. Their answers were summarized, and in two additional rounds of consultation, they were required to rate the importance of each reason.
  • As a result, a ranking of the most important rationales behind the choice of fentanyl administration form was obtained.

Nominal Group Technique:

  • The nominal group technique methodology works as follow: Participants meet in a session and complete a first round of independent opinions in writing about a particular topic along with its rationale. The results are summarized and distributed to participants. With the support of a moderator, participants expose and discuss their opinions for clarification and evaluation. Several rounds of independent opinions and ranking may be conducted. When the final round of ratings is carried out, the highest total positions are selected as the final decisions. Nominal Groups studies usually consist of four to five rounds
  • The Nominal Groups technique maximizes the compilation of information since all individuals inputs are considered, preventing people from dominating the discussion and encouraging minority views to be shared
  • It is a particularly useful technique since it gathers all experts at the same time and location, being a cost-effective and time efficient method
  • The Nominal Groups method requires an accurate pre-planning from the moderator and experts, and availability from experts since they are assembled together in a single session.

 

The following case study, allows to gain a better understanding of how the Nominal Group Technique works:

Case study: Identifying areas to improve pain management in hospitalized patients3

  • The objective was to identify the areas to prioritize interventions in the pain management for inpatients in a hospital from the USA
  • A multidisciplinary group of 27 health professionals participated in study.
  • In the first round, 94 ideas were generated. General and context-specific priority ideas were summarized and grouped into several categories. In the following rounds, participants were required to rate the importance of each idea.
  • Consequently, a ranking of the main priorities to improve pain control among hospitalized patients was set.

If you would like to gain further knowledge, you can explore the following case studies:

  • Centre for Disease Control and Prevention. “Gaining Consensus Among Stakeholders Through the Nominal Group Technique” Department of Health and Human Services 7 (2006): 1-3.
  • Davies et al., 2011S. Davies, P.S. Romano, E.M. Schmidt, E. Schultz, J.J. Geppert, K.M. McDonald. “Assessment of a Novel Hybrid Delphi and Nominal Groups Technique to Evaluate Quality Indicators. Health Services Research”, 46 (6pt1) (2011). 2005–2018.
  • Van E, Pitchforth T, Bishop C, Russell E. “Delphi method and nominal group techniques in family planning and reproductive health research”. J Family Planning Reprod Health Care (2006);32:4:249-252.

At ilS we are specialized in Primary Research in the Life Sciences field and we use both techniques for consensus building: the Delphi Method and the Nominal Group Technique while moderating Expert Panels. Based on our own experience accumulated during over 5 years, we have adapted those methodologies in order to make sure consensus is achieved in the most efficient manner for our Clients.

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REFERENCES

1Manual metodológico de elaboración de guías de práctica clínica en el Sistema Nacional de Salud. MSPS, 2007. Link

2Jacobsen R, Møldrup C, Christrup L. “Rationales behind the choice of administration form with fentanyl: Delphi survey among Danish general practitioners” Journal Opioid Management (2010);6(4):259-68.

3Peña A, Estrada CA, Soniat D, Taylor B, Burton M. “Nominal group technique: a brainstorming tool for identifying areas to improve pain management in hospitalized patients” J Hosp Med. 2012;7(5):416-20.

Personalized Medicine perspectives in the United States

By Alexandria Kyle-Hammer

p3The use of one’s genetic profile to inform and guide the diagnosis, treatment and even prevention of disease in individuals (i.e. personalized medicine),1  has made great strides over the last decade and is becoming increasingly popular and common as a treatment tool around the world. Although its use applies to the treatment of many diseases in various fields of medicine, it is worth noting that particularly in oncology, the role of personalized medicine has been revolutionary.

A recent Nature Reviews article, Defining and Quantifying the Use of Personalized Medicines2 , where the authors use the following definition for personalized medicine, 1) “A medicine that has a US Food and Drug Administration (FDA) or a European Medicines Agency (EMA) label stating that its choice as a treatment must be governed by results from a companion diagnostic test” 2) “A medicine that has a label that recommends (but does not require) the companion diagnostic, and at least one authoritative professional organization also recommends use of the test to guide treatment”2 , analyzes the growth in the use of personalized medicine from 1998 to 2009.

When personalized medicine first began to be used in the 1990´s the United States quickly became the world leader in the per capita use of biological personalized medicine. However by 2007 the US was overtaken by the EU, specifically the 5 major markets of France, Germany, Italy, Spain and the United Kingdom (the EU5), and by 2009 the United States had also been passed by Japan. By the end of 2009 the U.S. market was 25% smaller than that of the EU5. In 2011 and 2012 only 8 out of the 69 new molecular entities (NME) approved by the FDA were personalized medicines (i.e. 11.5% of the NMEs).

With the great potential and many befits of personalized medicine it is important for the U.S. not to fall farther behind in this field. The article proposes that by studying over time the various geographical regions where the use of personalized medicine has been the most successful we may be able to draw conclusions about the policies and healthcare systems used that might be most useful in supporting the further adaptation of personalized medicine in the United States.

The article also offers several other interesting findings. One being that the majority of the usage and sales of personalized medicine has been focused in the area of Oncology, suggesting a great unmet need in the field. Many older drugs that were not previously used as personalized medicine have since been converted into personalized medicines, as it has become clear that they are more effective when used as such. An example of this is the drug Tamoxifen, which was commonly given to women with ER+ breast cancer. It became a personalized medicine when it was discovered that 65% of women taking the drug developed resistance due to a mutation in their CYP2D6 gene. Now women are genotyped for that specific mutation so that the right treatment is given to each breast cancer patient. This conversion of medicines already on the market to personalized medicines has impacted the growth of the field.

Although the overall use of personalized medicine is growing at a 22% Average Annual Growth Rate (AAGR) globally between 1998 and 2009, the United States is lagging behind when compared to Japan and the EU5.

The FDA and the US National Institutes of Health (NIH) have promised to invest heavily in the field to support the growth of personalized medicine and the effort to make it a reality in the USA. As part of this effort the FDA has released a set of guidelines to regulate the field of personalized medicine. Within the Agency they have also created a Personalized Medicine Staff (http://goo.gl/7FCkcr) dedicated to “addressing the opportunities and challenges associated with diagnostics used in personalized medicine”3.

While these efforts, along with others, are a step in the right direction the progress of personalized medicine in the US is still slow. Further investigation is needed to identify the essential driving factors of the growth of personalized medicine in order for it to reach its full potential as a treatment method. It is also possible that more “public funding for translational research, greater use of electronic medical records to better access patients’ test information, and incentives for developers to personalize both approved and investigational therapeutics”4 are needed to further drive the advancement of personalize medicine.

1 http://ghr.nlm.nih.gov/glossary=personalizedmedicine
2 Hu, Sean X., Murray L. Aitken, Arnold L. Epstein, Mark R. Trusheim, and Ernest R. Berndt. “Defining and Quantifying the Use of Personalized Medicines.” Nature Reviews Volume 12 (2013): 896-97. 1 Dec. 2013. Web.
3 http://www.fda.gov/downloads/scienceresearch/specialtopics/personalizedmedicine/
ucm372421.pdf
4 See footnote 2