MA

Guest article by Anabela Farrica

The Medical Affairs (MA) function is known to be a rather broad and hard one to define. (1)  Its operations are essentially founded on the scientific exchange with internal and external stakeholders, with the ultimate goal of translating medical science into value – not only value for the business, but also, and most importantly, value for the patient through an adequate and safe use of their products. The methods MA groups employ to support and fulfill this goal are of great diversity: scientific congress support; advisory board realization; data generation (by providing support to both pre- and post-marketing studies); implementation of educational programmes for healthcare professionals (HCP) and patients; promotional material review; providing answers to medical enquiries; and many others. (2)

The success of a MA group is highly dependent upon the understanding, by its members, of how the regulations surrounding their activities apply and, at the same time, of the commercial implications of their work. (1) Maintaining this delicate balance is no small task, especially considering the intensified public and regulatory scrutiny applied to the pharmaceutical and medical device industries. (3)

Furthermore, the job of MA has become increasingly complex, not only because of this scrutiny on the industry, but also because there is a host of external challenges that increases the expectations for these professionals:

  • HCP’s information needs have grown and become more demanding; (4)
  • A sharper focus on Risk Management; (5)
  • The growing prevalence of chronic diseases; (5)
  • An increased industry focus on niche diseases, with products characterized by a larger amount of complex scientific information; (5)
  • The emergency of new types of data (e.g. Real World Data) and an expanding number of its users; (6)
  • A rise in digital media as sources of medical information that have made patients a pivotal stakeholder in today’s industry communication initiatives. Specifically, there is a growing interest on the patient’s satisfaction as a consumer of care. (5)
  • A more demanding market access environment, with strict pricing and reimbursement policies that difficult access to the often costly therapeutic novelties. (5)

Additionally, the focus of a MA team on the sound scientific interpretation of drug-specific and data-specific information and its implications has been recognized by the companies has a valuable asset for strategic planning. In this role, the MA professionals have become crucial by helping to bridge science with commercial aspirations. (6)

In the face of these challenges, MA’s purpose of enhancing medical care will not only require a deep comprehension of product knowledge, but also a robust, informed view of the needs, requirements, expectations and perspectives of various healthcare stakeholders. (7) Advisory boards, while not a novelty for MA teams, are of particular relevance as a strategy for obtaining non-binding but informed guidance on a range of business aspects. (8)

Advisory boards are commonly held with Key Opinion Leaders (KOLs) in the company’s fields of expertise in order to obtain expert feedback on various aspects related to a product or disease state. (2) An effective advisory board is a precious tool to gain insights on possible research opportunities, including guidance on clinical development and trial protocols, as well as unmet medical needs that might drive future clinical strategies. Input on marketing strategies, plans or materials can also be acquired through these meetings. (2, 7) By allowing a direct engagement with the medical community, advisory boards help pharmaceutical companies in product development, data generation, strategy refinement and in creating relevant and reliable educational and promotional content. (7)

Advisory boards can, thus, take place virtually at any stage of product development, depending on the needs identified by the company. However, as the regulatory requirements get tougher and payers look for ever more clear-cut proof of products’ value, MA should seek out to include insights from a broad range of external medical decision-makers and influencers into early clinical development. (7, 9) Expert input might guide, for instance, the risk management plan for clinical trials and the identification of the ideal target groups for the product, to ensure optimal clinical effect is achieved. The importance of this input grows as the a product moves along the development and regulatory pathways – especially as it progresses onto Phase III or Pivotal Clinical Trials, which are often determinants of product success. It might be beneficial to taken this type of advice from both Global and Regional advisory boards, to take into account regulatory and clinical differences, or even physiological variations between populations. (10)

Once a drug is licenced, advisory boards might be useful to: (2)

  • Understand the appropriateness and effectiveness of marketing strategies;
  • Identify and design the necessary post-marketing clinical trials;
  • Perfect the medical and/or patient education measures that have been adopted;
  • Increase understanding of how satisfied physicians and patients are with the product and of how to best fill in the gaps and voids that may exist.

A successful advisory board is one that generates actionable deliverables and that fosters positive relationships with prominent members of the scientific community. (7) The trend for tighter budgets and the pressure to do more for less represent great challenges to MA professionals. To maximize the return on investment, it is important to invest optimal resources in structuring an advisory board appropriately. (8) Cost reduction should not mean that meeting quality is compromised, as poorly executed advisory boards fail to provide companies with instructive medical insights and added-value recommendations from the medical experts in attendance. (7) Some of the elements to consider in an advisory board to ensure the desired outcomes are:

  1. Have a clear objective: the MA team responsible for organizing the advisory board must set a focused goal that not only justifies holding the meeting, but will also determine its members and guide the discussion. (11)
  2. Choose the right people: ideally, the group of advisors should be representative of the variety of skills, expertise and experience related to the specific topic under discussion. This means that the board should not necessarily consist of product supporters only, for example. In some cases, the best insights and ideas come up when opinions diverge. (7) Having members that are good communicators and are open-minded is also important to foster discussion. “Big names” can be a powerful addition to an advisory board, but an uneven peer group, with a mixture of elements with various levels of notoriety or responsibility, may create barriers instead of opportunities. (12)
  3. Clarify expectations: when inviting an expert to join an advisory board, it is essential to lay down the expectations the MA team has for the meeting in terms of time, areas where help is being sought out and end result. If the object of discussion includes private information, members should be notified of the need to sign a confidentiality agreement. (12)
  4. Compensate the participants: money should not be the main motivator for participation in an advisory board. Nevertheless, it is good form to provide some sort of compensation, such as meals, travel expenses or even a small fee. Members that feel appreciated will be more willing to engage in active discussion. (12)
  5. Make sure board members are prepared: distributing information to board participants before the meeting increases the chances of an interactive, successful meeting. (11) Pre-readings or other materials ensures that all participants are equally prepared, thus facilitating the flow of the session and promoting an active and open participation by the group.
  6. Assign a great moderator: preferably a person from the MA team that is familiar with the details of the issue for which input is being collected. This helps energizing the meeting onto an end result that is effective and actionable. (7)
  7. Organize the meeting appropriately: from a member-driven agenda that stimulates interest to a meeting location that is comfortable and free of distraction, a carefully thought out meeting is essential to maximize potential benefits. (12)
  8. Diversify the communication methods: typical Powerpoint presentations may not work for everyone, due to the natural heterogeneity in learning and group discussion styles. Handouts with relevant graphics, videos or questionnaires are interesting alternatives to consider. (7)
  9. Assess the meeting: obtain feedback immediately after an advisory board ends. Self-assessment and monitoring are key. (11)
  10. Convert meeting results into action steps: in order for the core objective of the advisory board to be fulfilled, the insights gained from the meeting should be capitalized under the form of practical company activities. (7) A board where the solicited feedback results in action steps is a successful board. (2)
  11. Follow-up with board participants: keeping the members of the advisory board informed on the outcomes of the meeting is vital to foster continued scientific exchange with these KOLs. Updates on what is being planned and on what the company has worked on as a consequence of the meeting should be made on a regular basis.

These practices ensure advisory boards are founded on professional dialogue and informative feedback, which can help identify key issues needing clarity or exploration and set a framework for value-added change. (13)

In the (recent) past, the biopharmaceutical industry was under a considerable amount of criticism around the unduly use of allegedly scientific advisory boards as promotional events to influence physician’s prescribing habits. Accusations of promotion of either unlicensed products or indications emerged, as well as suspicions of disproportional compensation and hospitality given the nature of the meetings. Nowadays, these and other types of interactions between the industry and healthcare professionals are governed by a set of rules: European and/or national law; companies’ Codes of Conduct; and ethical standards defined by EFPIA and by national associations of the pharmaceutical industry (APIFARMA, in Portugal) that have been increasingly advocating for a culture of transparency. (10)

Advisory boards have been a part of the MA landscape for a long time, functioning as sources of expert insight into a wide range of issues related to products’ lifecycle.  Today, they are more useful than ever, as regulatory requirements get tougher and patients, payers and healthcare providers demand more and more diverse clinical data and health outcomes information to prove product vale. Effectively managed advisory boards help MA teams to achieve this and more – as the ultimate goal of the knowledge gained should always be to improve the quality of life for patients. Biopharmaceutical companies are expected to seek and employ innovative ways of conducting advisory boards and capitalizing on the wisdom gained, so as to balance the value added to their clinical and commercial goals with the compliance with the relevant codes and laws.

References

  1. Wolin MJ, Ayers PM, Chan EK. The Emerging Role of Medical Affairs within the Modern Pharmaceutical Company. Drug Information Journal. 2001;35(2):547-55.
  2. Evens R. Medical Affairs and Professional Services. In: Evens R, editor. Drug and Biological Development: Springer US; 2007. p. 240-74.
  3. Werling; K, Carnell; H, McCormick; D, LLP; M, Chicago I. Focus on Life Science Compliance: The Evolution of Medical Affairs Departments. AHLA Connections. 2011;15(11).
  4. Bloom; L, Andre; T, Chandran; P, Dabbs; E, Keen. K. Raising the Bar in Biopharma Medical Affairs: Three Critical Success Factors Boston Consulting Groups: Boston Consulting Groups; 2013 [cited 2015 27-06-2015]. Available from: https://www.bcgperspectives.com/content/articles/biopharmaceuticals_raising_the_bar_in_biopharma_medical_affairs/.
  5. Morgon P. Medical Affairs. CEGEDIM, 2014.
  6. Evers; M, Fleming; E, Ghatak; A, Hartmann; J, Nathoo; A, Piervincenzi; R, et al. Pharma Medical Affairs 2020 and beyond. McKinsey & Company: McKinsey & Company, 2012.
  7. Dyer; S, Tolmachev. A. Nine Key Elements To Ensure Advisory Board Success pm360online: pm360online; 2014 [cited 2015 27-06-2015].
  8. Best Practices L. New Study Presents Insights to Advisory Board Effectiveness in the Pharmaceutical Sector prnewswire.com: prnewswire.com; 2015 [cited 2015 27-06-2015]. Available from: http://www.prnewswire.com/news-releases/new-study-presents-insights-to-advisory-board-effectiveness-in-the-pharmaceutical-sector-300076091.html.
  9. Presson J. ADVISORY BOARD FUNCTIONS EXPANDING IN PHARMA INDUSTRY Cutting Edge Information: Cutting Edge Information; 2013 [cited 2015 27-06-2015]. Available from: https://www.cuttingedgeinfo.com/2013/advisory-board-functions-expanding-pharma-industry/.
  10. Liftstream. Scientific Advisory Boards and the Impact of Compliance Liftstream: Liftstream; 2015. Available from: http://www.liftstream.com/blog/scientific-advisory-boards-and-the-impact-of-compliance/#.
  11. Moltz B. 10 Steps To Forming An Effective Advisory Board American Express American Express 2011 [cited 2015 27-06-2015]. Available from: https://www.americanexpress.com/us/small-business/openforum/articles/10-steps-to-forming-an-effective-advisory-board-1/.
  12. Stengel G. Ten Tips to Creating an Effective Advisory Board Stengel Solutions: Stengel Solutions; 2003 [cited 2015 27-06-2015]. Available from: http://www.stengelsolutions.com/tips19.htm.
  13. Joyce D. Medical Affairs: The Catalyst for Effective Medical Communications. PharmaVOICE. 2013:46-7.

Dozens of inspectors of the Policia Judiciária(Judiciary Police – PJ) are conducting a search and seizure operation at the headquarters of the Portuguese Bial Group, in Porto, and at the pharmaceutical delegations in Lisbon. It was initially believe that the Coimbra delegations were also being investigated, but this is currently not the case.

The search warrants were issuedby the Departamento Central de Investigação e Acção Penal (Central Department of Investigation and Penal Action (DCIAP))and the investigating judge Carlos Alexandre.

This operation is due to a suspected corruption case involving senior executives of the Bial Group, sales representatives, and hundreds of physicians allegedly paid to participate in scientific studies and to prescribe medicinal products marketed by the Portuguese company.  These include bonuses paid to doctors for false prescriptions of drugs that benefited from a high reimbursement rate from the National Health Service, some of which reimbursed at 100%.

The operation currently only counts with search warrants, with no arrest warrants issued thus far, but according to the Público Newspaper, later today defendants might be named in this case.

The process is centered on signs of, among other crimes, active and passive corruption for lawful and unlawful action, aggravated fraud, and document falsification.

Bial´s drug portfolio includes a number of generics, from Diazepam, Acid Folic products and Rivestigmine, to the first original drug molecule developed in Portugal, Eslicarbazepine acetate (marketed as Zebinix in Europe and as Aptiom in the US), for the treatment of epilepsy, and the upcoming Opicapone, a COMT inhibitor for Parkinsons´s Disease.

We will update the website as the news progresses.

July 6, 2015 | By Márcio Barra

Many hospitals in Portugal lack adequate support services for Clinical Trials. (Image source: Roche.pt)

All Portuguese hospitals will have to create a Research, Clinical Epidemiology and Public Health service until June 2016, and bigger hospitals will have to do so until the end of 2015, according to Order (extract) No 7216/2015, published on July 1st on the Diário da República website.

This requirement comes from the fact that the majority of hospitals and health centers in Portugal do not have oriented services to support these kinds of research activities, such as clinical trials, observational trials, and epidemiological studies . These new units are an attempt to fill this gap, and as such, the responsibilities of the Research, Clinical Epidemiology and Public Health services will include:

  • Collaborate in the provision of hospital care and activities that promote general health in the population, including planning, monitoring and evaluation of health care and organization of health services
  • Support and promote the participation of the hospital in which they are inserted in public health programs
  • Support for epidemiological, clinical, public health and health care research activities, by providing research enterprises for health professionals, training in research methodology, promote good research practices, and providing human and logistical capacity for research activities
  • Promote hospital collaboration in research projects led by third parties and participation in research networks
  • Prepare hospitals for emergencies, such as epidemics, disasters or other threats to public health
  • Support or ensure the planning, creation, development and management of hospital records, national health registries, and data relating to the literacy of health professionals regarding computer systems and statistics
  • Propose, manage and collaborate on intervention programs for disease prevention and health protection

Moreover, a Research, Clinical Epidemiology and Public Health service will be able to include many different professional groups (physicians with experience in clinical research, nurses, and biostatisticians, among others. No mention of clinical research coordinators), which may, with the permission of the hospital board, accumulate functions with other services.  The Diário de Notícias is reporting that physicians will be able to devote 75% of their time to research activities, and that there will be incentives for physicians who purse research, such as salaries increase or career progression.

Research, Clinical Epidemiology and Public Health services should must become operational by December 31, 2015, in Hospitals, Medical Centers or Local Health Units of Groups III and IV, according to Decree No. 82/2014 of April 10. These include:

  • Centro Hospitalar e Universitário de Coimbra, EPE
  • Centro Hospitalar de Lisboa Central, EPE .
  • Centro Hospitalar Lisboa Norte, EPE
  • Centro Hospitalar de São João, EPE
  • Centro Hospitalar Porto, EPE .
  • Instituto Português de Oncologia de Coimbra, Francisco Gentil, EPE
  • Instituto Português de Oncologia de Lisboa, Francisco Gentil, EPE
  • Instituto Português de Oncologia do Porto, Francisco Gentil, EPE
  • Centro de Medicina Física de Reabilitação do Sul
  • Centro de Medicina de Reabilitação da Região Centro – Rovisco Pais
  • Centro de Reabilitação do Norte
  • Centro Hospitalar Psiquiátrico de Lisboa
  • Hospital Magalhães de Lemos, EPE

All remaining Hospitals, Medical Centers or Local Health Units have until June 30, 2016 to implement this service.

MS fight

June 30, 2015 | By Márcio Barra

Genentech, a member of the Roche Group, announced today that its Multiple Sclerosis (MS) agent Ocrelizumab, for people with relapsing multiple sclerosis, met its main endpoints in two final-stage Phase III clinical trials (the OPERA I  and OPERA II  studies)

Ocrelizumab is a humanized anti-CD20 monoclonal antibody that acts as a suppressor of CD20-positive B cells, a type of cell thought to be behind myelin destruction in MS. Other monoclonal antibody treatments for MS include Daclizumab (currently in clinical trial phase) and Alemtuzumab (commercialized as Lemtrada).

The OPERA I and OPERA II phase III studies recruited a total of 1656 participants with relapsing remitting MS who took either ocrelizumab 600mg every 6 months or interferon beta 1a (Rebif, an injectable MS treatment marketed by Merck Serono) three times per week for approximately two years. Both studies shared the same set of endpoints. Primary endpoint was annualized protocol-defined relapse rate (ARR) at two years (96 weeks). Secondary endpoints included time to onset of confirmed disability progression, and safety related endpoints such as the total number of T1 Gadolinium-enhancing lesions, and total number of new and/or enlarging T2 hyperintense lesions as detected by brain MRI.

In the press release, Roche stated that ocrelizumab “significantly reduced” relapses, alongside a reduction of disability progression compared with Rebif, as measured by the Expanded Disability Status Scale (EDSS), the standard MS evaluation tool.

Regarding the safety endpoints, Roche stated the drug showed a similar number of adverse effects as Rebif, the most common being infusion-related reactions involving the immune system. Ocrelizumab infusion also led to a significant reduction in the number of lesions in the brain compared with Rebif, as observed by MRI scans.

However, no “real” results were shared by Roche, as the company declared that further analyses of the OPERA studies are ongoing, and detailed data will be presented at an upcoming medical congress. Roche is also preparing to start filling for regulatory approval in 2016, according to Sandra Horning, M.D., chief medical officer and head of Global Product Development:

“Ocrelizumab showed remarkable improvements over a standard-of-care medicine across clinical and imaging endpoints in two pivotal studies. Ocrelizumab has the potential to make a meaningful difference for people with MS, a chronic and debilitating disease. Based on these compelling results, we plan to submit the data for review to U.S. and EU regulatory authorities in the first quarter of 2016.”

Alongside the OPERA studies, Ocrelizumab is also being studied in a currently ongoing Phase III clinical study entitled ORATORIO, a placebo-controlled study in people with Primary Progressive Multiple Sclerosis.

March 27, 2015 | By Márcio Barra

Kalydeco, a new orphan drug priced at over US$300,000 per year

A new study released today by the WHO Regional Office for Europe provides an in depth look at the challenges faced by European Member States health systems by the introduction of new, costly therapeutic entities, and the troubling economic burden they bring to the Member States.

As an array of new drugs reach Europe, healthcare expenditure with new drugs is increasing at an accelerated pace. Some of new, costlier drugs include Gilead’s Hepatitis C drug Sofosbuvir (Sovaldi), orphan drugs with prohibitive price tags, and new anti-cancer agents costing $6,000-10,000 a month.

The report’s main takeaway message is that European governments need to cooperate and encourage collaboration between payers on standards and criteria for evaluation of benefits and cost–efficiency of new medicines, seeing as some member states do not have mechanisms in place to evaluate cost-effectiveness. Governments should also promote transparency on price deals between countries with price regulatory agencies (such as the UK’s NICE) and countries with less developed health technology assessment methodologies.

The study highlights the fact that medicines should be priced according to the added therapeutic value that they bring to patients, and pricing systems should distinguish and reward meaningful clinical innovation. However, most countries, including Portugal, still rely on external reference pricing methods. This pricing system has a host of limitations including arbitration of the targeting price, launch delays (as countries with more expensive prices tend to have new drugs available earlier)  and the lack of incentive for innovation. Only Germany, Sweden and the United Kingdom do not use external referencing pricing, but instead free pricing mechanisms for pharmaceuticals.

While external referencing pricing remains the most popular option, more and more member states are starting to adopt health technology assessment to guide their reimbursement decisions, following the steps of  UK’s NICE, which is responsible for conducting and reviewing cost effectiveness analysis for new drugs, relying particularly on the quality‐adjusted life-year (QALY).

You can read the full report here

March 24, 2015 | By Márcio Barra

amiosov

Last week, a warning letter was issued by Gilead to doctors informing that the combination of Gilead’s innovative hepatitis C drugs Harvoni (sofosbuvir/ledipasvir) or Sovaldi (sofosbuvir) with amiodarone (an antiarrhythmic drug generally reserved for difficult cases ) may cause potentially fatal heart arrhythmias.

The news comes after an FDA label update of the drugs, following a series of reports from Gilead describing symptomatic bradycardia events in nine patients who took the medications along with amiodarone. Seven of the nine patients were also taking a beta-blocker. One patient died from cardiac arrest after treatment and three others received a pacemaker.

The FDA label update provides further information on the bradycardia events, detailing that they generally occurred within hours to days, but there were cases where the events happened up to 2 weeks after initiating Hepatitis C treatment. The effect mechanism of this interaction is still unknown. The label update informs that, for patients who have to be prescribed with amiodarone, they should undergo cardiac monitoring for 48 hours after first administration and then daily heart-rate monitoring either done in the outpatient or in a home setting for 2 weeks. The same monitoring rules should be followed for those who discontinue amiodarone, due to the drug´s long half-life.

While the combination can be potentially fatal, Wall Street analysts are reporting that the news will have”zero impact” on sales.  This is due to the fact that there are a relatively small number of hepatitis C patients taking Gilead’s new drugs alongside amiodarone. Regional prescribing practices could also be a factor here, seeing as most of the cases of seriously slow heart rates occurred in France, where amiodarone is more widely prescribed.

Sources:

FDA

WSJ Pharmalot

March 19, 2015 | By Márcio Barra

 

The Bial group announced today that the BIAPARK I phase III clinical trial study evaluating Opicapone, an investigational peripheral COMT inhibitor for people with Parkinson´s Disease, obtained positive results. This is the second new investigational drug developed by Bial, following Zebinix (eslicarbazepine acetate).

Opicapone is a selective and reversible COMT inhibitor, to be used in combination with L-DOPA/ Carbidopa or L-DOPA/benserezide. The drug increases L-DOPA plasma levels when administered alongside L-DOPA, through inhibition of the O-methylation of L-DOPA by the COMT enzyme, thus increasing L-DOPA´s plasma half-life. In the BIAPARK I study, the drug was compared to Entacapone, another COMT inhibitor, and placebo. The study results, which will be presented today at the 12th International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders in France, show that the daily intake of 50 mg of Opicapone led to a significant reduction (2 hours) of the OFF-time period compared to placebo. Moreover, Opicapone was considered overall safe and well tolerated.

Currently, there are two COMT inhibitors available on the market, Tolcapone and Entacapone. Of the two, Tolcapone is the more efficacious, reducing OFF time in 98 minutes when compared to placebo, versus 41 minutes for Entacapone. Tolcapone´s use however, is hindered by its potential hepatic toxicity. Both drugs also require multiple dosages over the day, while Opicapone is once-daily.

Professor Joaquim Ferreira, ‎Professor of Neurology and Clinical Pharmacology at the University of Lisbon, said, “In the last 10 years, there have been few new treatment options in Parkinson’s disease. Opicapone intends to fulfil the need for a more potent COMT inhibitor.”

Professor Andrew Lees, Professor of Neurology at the National Hospital for Neurology and Neurosurgery, London, added, “Opicapone offers an important alternative to the currently available COMT inhibitors, with convenient once-daily dosing.”

The BIPARK I clinical trial recruited a total of 600 patients over 106 study centers spread over Europe, including Portugal.

Sources:

Bial 

A systematic review of catechol-0-methyltransferase inhibitors: efficacy and safety in clinical practice.