In an ideal world, healthcare professional (HCP) education about pharmaceutical and medical device therapies is always distinguishable from promotion. Yet the reality is that medical education and promotion can sometimes cross paths such that their distinction becomes blurred. Indeed, one could argue that medical education conducted by pharmaceutical and device companies is a form of promotion as the reality is that there is ultimately a product to sell. On the other hand, since the pharmaceutical/medical device company researched and/or developed the product, it can also be argued that the company is amongst those best placed to educate HCPs about that product.
Medical education and promotion are quite different activities:
However, when does the line between these two distinct activities become blurred? The following three cases, adjudicated by the Medicines Australia Code of Conduct Committee (“Committee”), help to shed some light.
Case 1. Selective data as medical education
Scientific or technical information provided to HCPs should be fair, accurate and balanced, particularly comparative information between therapies, to support clinical decision-making. Yet what if a pharmaceutical company’s Medical Liaison team was to distribute an email to HCPs containing selective excerpts of efficacy and safety data from a regulatory agency assessment report to favourably compare its therapy with a competitor product? This was the case where the selective extraction of data in an email was consequently considered by the Committee to be unfair, unbalanced and misleading to HCPs.(1) Being extracted data, it was without relevant context and omitted key report information about the competitor therapy, The selective email information thus did not accurately reflect the equivalent report content and would likely have the effect of discouraging use of the competitor therapy, while encouraging use of the company’s product. Although the full report was provided in the email, the Committee concluded the email content was promotional information and not medical education as it provided selective data to discredit the competitor therapy.(1)
Case 2. Off-label information as medical education
Companies are responsible for ensuring therapy content at medical educational meetings aligns with the approved Product Information and to brief HCP speakers accordingly when presenting at these events. However, at one meeting (one of a series of educational meetings sponsored by a pharmaceutical company) the international HCP speaker presented study data on the long-term use of a drug for up to 12 years, although its approved treatment duration was 12 weeks.(2) Moreover, the data presented was for a different compound of the drug moiety to that approved in Australia, which was indicated for a maximum of 12 weeks’ use. The Committee concluded the educational content focused on a product not available in Australia, although containing the same drug moiety, and would encourage off-label prescribing for long term use which, in turn, had potential safety implications for patients. In this case, educating on the long-term use of an unapproved compound of the same drug moiety was tantamount to off-label promotion of the long-term use and associated safety of the approved product in Australia.(2)
Case 3. Manufacturing tour as medical education
The primary objective of HCP attendance at company sponsored medical education events is to enhance medical knowledge and the quality use of medicines. Companies must be able to justify the event’s educational content and its relevance to HCP attendees’ area of expertise. However, would an overseas manufacturing facility tour organised (and sponsored) by a pharmaceutical or medical device company qualify as necessary HCP education? On the surface, one of two extremes could be argued – either it is education overkill or an example of promotion disguised as medical education.
Yet it was neither of these extremes in a case adjudicated by both the Medicines Australia Code of Conduct Committee and Appeals Committee where a pharmaceutical company had organised for a group of HCPs to visit its biotechnology manufacturing facility following their attendance at a nearby third party scientific meeting.(2) The tour aimed to provide HCPs experiential understanding of the manufacturing process – its complexities, challenges and quality standards – for a specific biological therapy by seeing it first-hand. This would help to build their confidence of the process, as well as knowledge of potential patient reactions to the therapy’s complex protein molecules. The HCPs would also benefit from interacting with the R&D and manufacturing process personnel, which in turn could benefit patients. The Appeals Committee accepted the appropriateness and relevance of the tour for these reasons and so overturned the Code of Conduct Committee’s view that the purpose was to promote the company’s biological product, encouraging HCPs to continue prescribing and recommending. Of relevance is that there was no biological substitute for the company’s product, while other companies had held similar manufacturing plant tours for HCPs in educating on the complexities of biological therapies.(2)
Erasing the blur
The above mentioned cases show that the line between medical education and promotion is not always clear. Rigorous scrutiny in the planning of medical educational activities and content – ideally via a quality control process involving various stakeholders who can provide multiple perspectives – is therefore important to minimise the risk, intentional or unintentional, that the education becomes, or is perceived to be, promotion.
These cases also illustrate the importance of context. In Case 1, the selective use of data emailed to HCPs, which was non-contextualised, showed how incomplete information can easily morph from education to promotion, whereby the data becomes distorted, biasing one therapy over another. In Case 2, where an educational meeting focused on the long-term treatment duration of an unapproved compound with the same drug moiety as the approved product indicated for short-term use, HCPs will likely be encouraged to prescribe the latter for long-term use. Whether this effect was inadvertent or not, the meeting’s educational value was consequently outweighed by the promotional goal. Case 3 shows that even when an educational activity is consistent with industry standards and benchmarks and there is a broader relevant context to justify it – in this example the need to provide HCPs experiential learning about a complex biologicals manufacturing process that could not realistically be provided another way – the (mis)perception of promotion disguised as education may still arise.
Medical education and promotion are both key activities conducted by pharmaceutical and medical device companies. Our dedicated Medical Affairs team at CRC is well equipped to help plan and implement a wide range of impactful, yet compliant educational and promotional review activities for healthcare industry clients, ensuring the line between medical education and promotion is clear.
Systematic reviews and meta-analyses can be powerful tools for generating the evidence needed to inform clinical decisions, reimbursement decisions and the development of clinical practice guidelines (1,2). In the hierarchy of evidence based medicine (EBM), where clinical evidence is ranked according to the strength of freedom from bias,meta-analyses are ranked at the highest level for informing healthcare related decisions(3).
Systematic review versus meta-analysis
A systematic review aims to address a specific clinical or scientific question using a comprehensive plan, literature search strategy and explicit selection criteria to identify relevant studies, assess the methodologic quality of these studies, explore differences among study results and qualitatively and/or quantitatively synthesize their findings(4).
Meta-analysis is a statistical method conducted after a systematic review that combines data by drawing on the power of multiple studies to inform and quantify the efficacy, safety and/or utility of a healthcare intervention.Specifically, meta-analysis uses statistical techniques to synthesise and quantitatively summarise the results of individual studies. This increases the overall sample size and thus improves the statistical power of the analysis and precision of the treatment effect estimates (5–7).
The value of a meta-analysis is that where the size and direction of the treatment effect is consistent among studies, it confirms this common effect. Where the treatment effect is quite variable among studies, meta-analysis can help to identify the reason(s)why, which is also informative to clinical decision-making.
Are all meta-analyses the same?
There has been some debate in the literature about the types of studies that should be included in a meta-analysis to ensure they can inform healthcare decisions(8–10).As observed by Pickup (2013), meta-analyses can be classified as one of two distinct types, i.e. those that:
Regarding healthcare decisions, it is important that clearly defined methods are used to identify and examine appropriate patient cohorts with the relevant baseline demographic and disease characteristics to properly represent the target patient population for whom the therapeutic efficacy,safety, cost-effectiveness and optimal use of therapies is being considered by healthcare decision-makers(10).
Literature summary meta-analyses
Meta-analyses that include only randomised controlled trials (RCTs) as the highest level of study evidence in the EBM hierarchy, such as those conducted according to the Cochrane Collaboration Guidelines, have been described as “literature summary meta-analyses” (11,12). RCTs are favoured for having a more valid study design compared with other types of studies, whereby randomisation removes confounding and the double-blind process minimizes biases such as the placebo effect(8).
However, it can also be argued that including only RCTs in a meta-analysis may dilute the results. For example,the dilution may come from including less relevant RCT studies that contain a broader population of individuals who may not all be relevant to the clinical or reimbursement question being asked about the effect of a healthcare intervention on a particular patient segment (8,10).
Furthermore, excluding observational or non-RCT studies can also result in valuable information not being captured such as the duration of treatment effect over a longer patient follow-up period.Therefore, literature summary meta-analyses may be suboptimal for real world decision-making and indeed, even misleading, where decisions about clinical effectiveness and cost-effectiveness require examination of the entire body of evidence for relevance to real world patient populations and use, as opposed to only RCTs as the highest quality of evidence (10).
‘Decision-making meta-analyses’, as described by Pickup 2013,are designed to assess all relevant studies that include the target patient segment for the healthcare intervention of interest(10). These meta-analyses may include patient data focused on a particular level of disease severity or patients with a specific treatment history. There is a growing consensus that the inclusion of observational studies in meta-analyses could be advantageous since they increase the size of the specific patient population of interest, can provide patient data over a longer time period and include other valuable information that cannot (logistically) be examined by RCTs, yet is more reflective of real world clinical practice (8,10,12).
An example of this is the systematic review and meta-analysis conducted by Pickup and Sutton (2008)who showed the benefit of including both RCTs and before/after (observational)studies in their analysis of continuous subcutaneous insulin infusion (CSII) versus multiple daily insulin injections (MDI) for controlling severe hypoglycaemia in patients with Type 1 diabetes(13).Although CSII is recommended by several national healthcare guidelines, previous meta-analyses had reported ambiguous results for the effect of CSII in controlling severe hypoglycaemia. However, Pickup and Sutton (2008) purposely focused on patients at risk of severe hypoglycaemia as the target population of interest who could potentially benefit from CSII by following a targeted study selection process.Consequently, they found the worst controlled subjects on injections had the most improvement on insulin pump therapy. They also reported that patients who attended clinic visits in the before/after studies were more likely to have had problems with glycaemic control than volunteers in RCTs.
By including a specific “at risk” patient group, the authors appropriately captured an important patient segment in need who could benefit the most from CSII, which was shown to be superior to MDI in reducing severe hypoglycaemia from both RCTs and the before/after observational studies(13). Importantly, the RCTs and before/after studies showed consistent results regarding severe hypoglycaemia reduction, although the magnitude of the difference favouring CSII over MDI was higher for the before/after studies.
Examples such as this show that when a meta-analysisis purposely designed to address a specific clinical or reimbursement question, it can fully inform the true value of a healthcare intervention – whether it be a drug, device or other intervention -for a specific patient population in need that is relevant to the real world clinical setting.
At CRC,our medical affairs capability is well equipped to conduct high quality systematic reviews and meta-analyses for a broad range of client situations relevant to clinical, regulatory,reimbursement, market access and other healthcare decision making.
Australia’s healthcare system is complex with both Federal and State Governments sharing the responsibilities of funding and delivering healthcare services, which are further split between public and private sectors (1). In making healthcare purchasing decisions, the Australian Government develops policies grounded on an evidence based medicine (EBM) approach (1, 2, 4). EBM harnesses data ranked according to its quality to inform decisions relating to health care policies and the approval of products for reimbursement (5). The preparation of high-quality data, such as systematic reviews and meta-analyses requires a high level of expertise and critical appraisal, therefore these resources provide a higher level of confidence and are therefore ranked at the top of the pyramid, as shown in Figure 1.
A recent health policy report by the Organisation for Economic Co-operation and Developments has flagged that Australia has the 5th most obese population among all OECD country’s (1). Additionally, the aging population is increasing (1 in 4 Australians will be over 65 by 2060) and this population has a higher need for health services (7, 8). Health service experts are concerned with the cost burden being placed on the healthcare system due to increasing levels of chronic illness and aging populations.
Value based healthcare (VBHC) combines the use of robust clinical data with cost-benefit analysis of real world data and a patient-centric approach, as shown in Figure 2. This system would see reimbursement based on quality of care and patient outcomes in the real world rather than the volume of procedures and patient visits (10). This approach aims to encourage the use of real world data via ‘pay for performance’ programs to extract greater value from the healthcare services provided (11).
In 2012, the Boston Consulting Group published a report analysing progress in developing infrastructure (patient registries and programs to capture quality data) to enable a VBHC system (12). Each country’s progress was examined using four categories; clinician engagement, national infrastructure, data quality and data use. Australia scored low in relation to readiness to implement a VBHC system, particularly in terms of data use and infrastructure. In 2016, 25 countries were examined for indicators of alignment with VBHC parameters (11). This assessment again described Australia’s overall alignment as moderate and noted that Government and major payers have not yet implemented plans for systematic change. While Australia has made some progress in terms of setting up disease registries, there is to date a lack of data sharing which reduces the usefulness of these registries (13).
Ultimately, it needs to be determined whether the upfront cost of putting in place new policies, infrastructure, disease registries and data analysis resources will ultimately result in long-term cost reduction and benefits to the Australian community.
Pay for performance solutions based on real world health outcomes aim to maximise value in the healthcare system for all stakeholders and countries are increasingly moving towards VBHC to more efficiently and effectively manage rising healthcare costs. Implementing VBHC solutions in Australia would require the collaborative efforts of these various stakeholders. CRC is well positioned to work with them in progressing potential VBHC solutions for clients by drawing on our extensive range of medical affairs and market access capabilities.
1. Organisation for Economic Co-operation and Developments. OECD Health policy in Australia. 2015.
2. Australian Department of Health. Evidence-based medicine and POCT. http://www.health.gov.au/internet/publications/publishing.nsf/Content/qupp-review~qupp-evidence-based-medicine-poct. 2013
3. Australian Department of Health. Evidence Based Practice. http://www.health.gov.au/internet/publications/publishing.nsf/Content/natsihp-companion-toc~invest-enablers~evidence
4. Australian Commission on Safety and Quality in Health Care. Australian Safety and Quality Framework for Health Care: Putting the Framework into Action: Getting started. 2016.
5. Sackett DL, Rosenberg WM, Gray J, Haynes RB, Richardson WS. Evidence Based Medicine: What it is and what it isn’t. British Medical Journal. 1996; 312
6. Glover J, Izzo D, Odato K, Wang L. Darthmouth College.
7. University CM. Evidence based medicine pyramid. http://libguides.cmich.edu/cmed/ebm/pyramid
8. Braithwaite J. Robust, evidence-based treatment will boost ailing medical system. The Australian. 2016.
9. Amalberti R, Nicklin W, Braithwaite J. Preparing national health systems to cope with the impending tsunami of ageing and its associated complexities: Towards more sustainable health care. Int J Qual Heal Care. 2016; 28(3):412–4.
10. Porter ME. A Strategy for Health Care Reform – Toward a Value-based System.
N Engl J Med. 2010; 363 (1): 1-3
11. The Economist Intelligence Unit. Value-based healthcare?: A global assessment. 2016.
12. The Boston Consulting Group. Progress Toward Value-Based Health Care. 2012.
13. The Economist Intelligence Unit. Value-based healthcare: A global assessment. Country Snapshot: Australia. 2016.
The popularity of consumer health and fitness wearable technologies (“wearables”) such as the Fitbit and Apple Watch is growing. As individuals are becoming better informed and thus, more empowered to play an active role in managing their health, it is unsurprising that the wearable market is expected to flourish. Health wearables, by definition, are autonomous, non-invasive technologies worn by individuals that are capable of measuring, tracking and storing data on physiological responses.1
While there is still uncertainty as to whether wearables directly contribute to positive behaviour change with regards to lifestyle habits and treatment adherence, they still have the potential to impact healthcare (Figure 2).2 2 By providing a platform that facilitates telemedicine and allows remote and ambulatory monitoring, wearables can significantly improve the provision of healthcare.1,2 1,2
As healthcare systems are becoming more focused on preventative actions, wearables will play an increasing role in patient care. Healthcare professionals (HCPs) and patients are able to access real-time longitudinal health data instantly, therefore, allowing wearables to assist in the management of chronic conditions such as diabetes.1-3 1-3
Wearables can be broadly classified as consumer general wellness device (e.g., health and fitness trackers like the Fitbit and Apple Watch) or regulated medical grade devices.4 4
The U.S. FDA has released a guideline to provide medical and wellness device manufacturers with clarity on the differences between general wellness and regulated medical devices.
In this guideline, general wellness products are categorised as products that are low risk and have an intended use that either:4 4
Wearables that fall into the above categories will not be required to comply with pre-market review and post-market regulatory requirements. Health wearables that are medical grade and pose a higher risk would be regulated by the U.S. FDA.
In Australia, medical devices are regulated by the Therapeutic Goods Administration (TGA) as per the Australian regulatory guidelines for medical devices (ARGMD) — which are currently under review — or the In Vitro Diagnostics (IVD) guidance.5,6 5,6 Health wearables, whether as a stand-alone product and for the software contained within, would fall under the definition of a medical device and would be classified according to the risk they pose (Table 1).
Given the technological advancements and innovation, an independent review of medicines and medical device regulation in Australia was conducted and published in March 2015.7 7 With regards to medical device regulation, the panel recommended that:7 7
At CRC, we understand what it takes to bring innovative new technologies to market. Health wearables will undoubtedly play a key role in healthcare, allowing patient and HCPs to work together to improve the diagnosis and management of conditions and diseases. Our expert team are ready to work with you to bring your innovations to those who need them the most.
1. Glaros, C. & Fotiadis, D.I. Wearable devices in healthcare. Intelligent paradigms for healthcare enterprises. Systems thinking. (eds B.G. Silverman, A. Jain, A. Ichalkaranje, & Jain, L.C.) 237-264 (Springer, New York, 2005).
2. Piwek, L., Ellis, D.A., Andrews, S. Joinson, A. The rise of consumer health wearables: Promises and barriers. PLOS Medicine 13, e1001953, doi:10.1371/journal.pmed.1001953 (2016).
3. Georga, E.I., Protopappas, V.C., Bellos, C.V. & Fotiadis, D.I. Wearable systems and mobile applications for diabetes disease management. Health and Technology 4, 101-112 (2014).
4. United States Food and Drug Administration. General wellness: Policy for low-risk devices. Guidance for industry and food and drug administration staff. (Silver Spring, 2016).
5. Therapeutic Goods Administration. Overview of the new regulatory framework for in vitro diagnostic medical devices (IVDs). (Canberra, 2011).
6. Therapeutic Goods Administration. Australian regulatory guidelines for medical devices. (Canberra, 2011).
Better access to healthcare information has raised patients’ expectations leading to them independently garnering an understanding of their condition and managing their own healthcare (Figure 1).1 Healthcare professionals (HCPs), therefore, are now no longer the sole decision-maker when it comes to healthcare choices.1,2 In response to the changing customer base, the biopharmaceutical industry is moving away from product-centric approaches to ones that are patient-centric.
A number of industry trends and patient factors are contributing to this shift from product-centricity to patient-centricity (Figure 1).
Decreased productivity and over-investment in R&D, saturation of large disease states and an increased focus on niche indications where it is difficult to get return on investment are all limiting the impact of product-centric approaches.3
Furthermore, patients are becoming more value-minded due to the rise in out-of-pocket expenses from new but costly health innovations and a growing range of lower-cost generic medicines following a rising number of patent expirations.3,4
Patients are increasingly key to approval and reimbursement decisions as regulatory bodies not only require real-world patient data but are also considering patient preferences and actively seeking patients’ input.1
Figure 1. Drivers shifting the decision-making from HCPs to patients.1,4
The biopharmaceutical industry, therefore, is under increasing pressure to create value to the patient while demonstrating commercial productivity and growth.
It is important to understand what it means to be patient-centric. Patient-centricity can be defined as acknowledgement that the needs of a patient or a distinct patient population — including their physiological, psychological and social needs — are at the core of decision-making.1,5
Increasingly, the industry is integrating patient-centric approaches across all stages of drug development from clinical trials to marketing (Figure 2). In doing so, companies will be able to create more value for patients through solutions that give patients the best possible health outcomes.4
Figure 2. Patient-centricity across all business functions.
Keeping patients at the core of key business functions can give biopharmaceutical companies a competitive edge for strong commercial growth as they develop and deliver meaningful health technologies (Figure 3).
Patient-centricity can inform clinical trial design and assist with patient recruitment and retention thereby driving the development and delivery of new, high-value health innovations.6,7 Furthermore, companies will be able to gain clarity on where their core activities and competencies are and how they align with patients’ needs thus, informing their strategy, decision-making and resource allocation.6
Figure 3. Patient-centric business functions can help drive commercial growth.6,8
Engaging and collaborating with patients and other stakeholders is a key step to acquiring important data on patients’ needs, behaviours, utilisation patterns and health outcomes.4 The amalgamation of this data can provide valuable insight and inform strategies for improving medicine use, increasing uptake and driving commercial growth (Figure 4).
Figure 4. Steps to becoming patient-centric.
When it comes to increasing revenue, productivity and growth there are three broad categories of patients to keep at the core of commercial strategies, those: 8
A white paper published by Kinapse Consulting suggested that significant culture shift would be required for companies to be successful in patient-centricity. This involves shifting their focus from disease to patient segments and providing integrated healthcare spanning the full spectrum of a patient’s needs, however this could prove challenging.4
A more achievable option encompasses multi-faceted strategies (Figure 5) to increase productivity, growth and demonstrate value should be targeted and optimised to HCPs and patients and aim to: 4,8
Figure 5. Patient-centric strategies for increasing product uptake.
At CRC we strive for quality and excellence as our expert team collaborate with our clients to develop innovative, patient-centric medical affairs solutions that will boost commercial productivity and growth. Our competitive advantage coupled with our extensive expertise in medical affairs and strong ties to the biopharmaceutical industry will allow us to reinvigorate your product portfolio, expand access and increase product uptake. We will achieve this through effective and innovative stakeholder engagement and management, medical communication and health education, brand planning and pre-launch and launch strategies.
CRC provides Medical Affairs solutions to the Pharmaceutical industry throughout the Drug Development Life Cycle. Our objective is to maximise the value of therapeutic compounds from pre-launch through to commercialisation and beyond.
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