Biopharmaceutical companies face many challenges that are increasing in complexity. They have always had to develop innovative and life-changing products and services that balance the needs of patients, their carers, HCPs, payers and shareholders. However, the regulatory requirements, payer expectations and management of new health technologies have become even more demanding. Although a difficult calculation over the longer term, it is widely accepted that only one in every four new products that enter development delivers a return on the investment made to get it there. That’s just covering costs. Making an acceptable return on investment for shareholders puts pressure on the one product that launches, to perform better than most actually do.
Several studies show that the number one reason for a new product to fail is the lack of good evidence for demonstrating that it meets the real needs and wants of customers. Other findings indicate that involving customers in the early ideation or later launch stages enhances new product financial performance directly and indirectly via acceleration of time to market, while customer participation in the development stage reduces the time to take the product to market. If the understanding of the range of customers’ needs is so important, the first priority is to find out how to discover these needs when developing new products and services. This can be a difficult task. In pharma particularly, it is often difficult to identify who is who.
Patients, customers and consumers
Biopharmaceutical companies operating in socialised healthcare markets do not benefit from the direct and more traditional consumer-provider relationship, enjoyed by many companies operating within other industries. Across the different markets, pharmaceutical companies do not generally supply prescription medicines directly to consumers. All prescription medicines require prescribing and dispensing through HCPs. HCPs make choices according to their perceptions of their (patients) consumers’ needs and likes and balance this with ever increasing budgetary justification.
Consumers have had some influence over what is purchased on their behalf by customers (see the recent reversal of NICE in providing a new Alzheimer’s medication) but there is often a conflict between the consumer’s demand of ‘I want’ and the buyer’s barrier of ‘I can afford’. This conflict is often evidenced by poor adherence and compliance rates. R&D and commercial functions must understand the different needs and perspectives of their customers and consumers and how to design addressing them, into products early to be successful. This is often easier said than done.
The almost inexhaustible amount of available information on diseases and their management, along with patient and carer dissatisfaction about the way they are treated by healthcare systems, has led to a fundamental shift in patient attitudes, rights and behaviours. Although several years ago, the ‘innovators’ (those well educated and keen to challenge conventional HCP-patient relationships) would cause some discomfort in the Doctor’s office, this has now moved to the early adopters and through to the beginning of the majority. More and more people are moving towards the ‘tipping point’ where they are disrupting the traditional patient/HCP relationship. They are proactively researching diseases, symptoms and treatment options online; conferring with other patients via social media and online communities; discussing and selecting care regimens with their physicians, pharmacists and carers. They are also using new wearable technologies and mobile health (mHealth) applications; and, even, taking the initiative to look out for and participate in clinical trials. It can be argued that patients are becoming much more like traditionally empowered consumers found outside of the medical world.
Patients, particularly those with chronic conditions, are the experts on their disease and its impact. As patients continue to become more powerful, the pharmaceutical industry needs to understand, use and benefit from the types of consumer research that are regarded as par pour le cours in other industries in which the true value of a pharmaceutical product is defined by those who will ultimately buy and consume it. In other industries, the input of consumers is typically sought throughout the entire product development process, from product conception, development and commercialisation options generation, through to launch and beyond.
Biopharma companies need to stop saying how ‘patient centred’ they are and take a close look at exactly what that means. We all get annoyed when we read about how the utility companies ‘listen’ to us and ‘really value their customers’ when there is significant evidence on the customer side that they don’t have a clue. Similarly, the biopharma industry is in the same situation but really does not believe it is. Like the board member of BT, we are so close to the situation that we can’t see or consider things from the viewpoint of real customers.
What to do about it
In spite of the wide-ranging recognition that capturing the patient perspective and behaviours during drug development is useful, pharmaceutical companies have yet to engage with patients systematically, to learn what matters most and what they value most, before developing a product. Many pharmaceutical companies tend to focus more on the commercial aspects of launch and post-launch activities. People working within commercial functions tend to have different objectives when engaging with patients than their colleagues in clinical functions. Because they may also lack the scientific or technical skill set to guide their clinical development programs, many decisions in clinical development are made without having fully elucidated ‘the options to meet the full range of needs that are not served in the marketplace that patients will be willing to fight for and value. Unfortunately, most biopharma companies rely on the traditional explicit techniques to uncover needs. This approach tends to resonate with rational scientific brains. This is a shame because as we know, most choices and decisions are made on a subconscious level.
Patients’ perspectives on disease burden, treatment experience, risk-benefit assessments, and unmet needs should be incorporated early, informing the drug discovery phase or during the shaping of the target product profile (TPP). If however, the methodology used to capture these needs is wrong, all downstream decisions will likely lead to flawed decisions. The TPP is a strategic guidance used by pharmaceutical sponsors to facilitate discussions and solicit feedback from regulators on the overall drug development program for an investigational product. Alongside other things underpinning a TPP, the patient voice can inform product attributes such as the route of administration, dosing, efficacy, acceptable levels of adverse events, and possibly even willingness to pay. Such an approach will lead to the development of a patient-centric TPP that reflects patients’ burden of disease, perspective on disease severity, and experience with existing treatment options. The heart of the argument is to make the most important aspects of the symptoms the primary endpoint of the trial. Companies should seek patient input in developing prototype TPPs and updating them throughout the drug development process. Note that we refer to TPP prototypes…the one TPP thinking has in our view led to some myopic decision making. This will help the organisation in identifying suitable criteria and metrics in shaping their products, which, in turn, will steer drug development toward medications that address how patients function and feel, including their quality of life and unmet medical needs. We believe that this investment will lead not only to a drug profile that resonates with unmet patient needs but also to an increased likelihood of favourable reimbursement decisions.
Establishing disease end points
Patient engagement early on in clinical development (from pre-Phase II to pre-Phase III) is crucial for developing a more comprehensive suite of endpoints beyond established measures, as well as for understanding which patients are candidates for study. From disease burden and cross-sectional clinical survey work, as well as some ideas on the potential benefits of a drug, a set of possible end points can be constructed for study in Phase II and, if successful, used in Phase III. That means spending more upfront at the Phase I-II stage to ensure a higher Phase III and commercial success. Depending on the disease, some exploratory work in Phase II might be needed in order to refine endpoints for Phase III. During Phase I and cross-sectional clinical survey work, some insight into the types of possible measures can be gained and compared with an existing menu of measures for concordance or reasonable context of use. If no existing measures are viable, then new measures may be warranted, which would require additional survey studies or Phase II ‘learn’ studies in which a variety of end points are explored. This is a fundamental change in the way clinical trials are currently conducted and has huge implications for the budgets and phasing of spend from Phase I-IV. It’s not necessarily about being BETTER than the competition.. but being DIFFERENT to them. This should be how the range of TPPs are presented… being better, means technicality being a high hurdle…. being different, means less technically challenging for the product but more technically challenging for the regulatory strategy.
Assessing benefit-risk profiles
At a later stage of development (post-Phase II trials), sufficient data are available to understand the disease burden, preliminary efficacy and the potential for adverse events. The product profile possibilities can be presented in a comprehensible manner to patients to assess what their reasonable goals of therapy might be relative to risks, to help in designing the endpoints and length of Phase III studies used to determine safety and efficacy. Again, it’s the methodology that’s important in gaining meaningful insights
Furthermore, clinicians must take into account the impact of therapy and disease on multiple body systems, which may go beyond traditional single domain measures. Overall, patient outcome is probably the integration of impacts on different domains, but the traditional single primary end point design often fails to capture the overall impact of treatment well. Understanding the integration of impacts is important in achieving an accurate assessment of the benefit–risk profile.
Evaluation of the risk tolerance of patients is potentially most effective when at least preliminary real efficacy and safety data are available. For example, given the lack of alternatives for treatment, patients with rare diseases and others with acute, life-threatening diseases may show significantly higher risk tolerance for novel therapies than developers or regulators. Furthermore, many rare disease patients must also weigh the risk of unchecked disease progression should they opt out of a trial. Decision-makers should take patient risk tolerance into account, and in some cases, this could be crucial in the approval process. However, these data should be viewed as one of several important data sets for regulatory review and not the sole basis for approval.