A bitter pill?
The ideal route of admin isn’t clear cut in the global marketplace
A key feature of any pharmaceutical product is its route of administration; the path through which the drug is taken into the body. This may be oral, injectable, transdermal or inhaled. Differences in route of admin can be critical points of differentiation for new pharmaceutical products, especially in crowded markets where multiple options are available. When conducting interviews with healthcare professionals, we commonly find that route of admin is often one of the first features they take into account (after efficacy and safety) when reviewing product profiles, and getting it right is fundamental to a product’s eventual uptake and market share. However the perceived benefits and drawbacks of different routes of administration can be more complicated than one might think. Market nuances can have far-reaching implications for drug formulation and device design.
Oral medications such as tablets and capsules are often seen as the holy grail by pharma companies and the reasons are obvious – no need for devices that can be costly and complex to use; no impact on healthcare system resources; convenient and easy for patients to take. This isn’t always the case though; geriatric patients especially may have difficulty swallowing pills. Sachets or liquid formulations may be valuable alternatives for these patients – but taste and volume can be important variables determining how acceptable these are.
With oral medications there is also the challenge of compliance; as soon as a patient is out of hospital, the responsibility for taking them is left entirely down to the patient (or their caregiver). Taking the example of birth control pills, while these are 99% effective if taken ‘perfectly’, the real world failure rate is around 9% per year. Pill size, branding, colour and even shape have been found to affect patient compliance, as well as the perceived effect of the medication. A 2015 study revealed people in the US, China and Colombia had strikingly similar perceptions of pills based on their appearance, with white pills consistently rated most effective at treating headaches (green were deemed least effective). The importance of testing and fine-tuning the detailed specifications of an oral medication should therefore not be underestimated.
Total pill burden is another important variable that needs to be considered when it comes to oral medications, with polypharmacy (the concurrent use of multiple medications) in the elderly population a common challenge. Fixed dose combinations, in which two active ingredients are combined in a single dosage form, can be a potential solution to this problem. These are notably more popular in some markets than others. While emerging markets have typically been receptive to fixed dose combinations, the Indian health ministry recently banned hundreds of fixed dose combinations in a move to weed out “irrational” drugs from the Indian market.
Injectables, when administered by an HCP, get around the compliance concerns; they may also have faster speed of onset because they provide a direct route to the bloodstream. However a lot of patients fear the needle which can lead to non-compliance. They can also be painful and inconvenient for patients, especially if they have to travel into hospital to receive them. This in itself can be far from straightforward for many patients in emerging markets where infrastructure is limited or concentrated in major cities. In the outpatient setting, medications administered via infusion also create resource burden for hospitals due to the need to provide staff to administer. Added to this, space in infusion centres can be limited and over-subscribed.
Frequency of admin goes hand-in-hand with form of admin in terms of the impact a product will have on resourcing. While the generally-accepted rule is the less frequent, the better, and in many therapy areas there is a drive to develop drugs with longer half-life, there is a point at which the benefits may be outweighed by drawbacks – for example where a less frequent admin is associated with a larger dose, which may take longer to administer and be more painful.
Injections can be intravenous, intramuscular or subcutaneous, with the latter potentially self-injected by patients at home. Here again, preferences can depend on how the key stakeholders trade off convenience and compliance. The trade-offs made may differ by patient age, with ‘more convenient’ routes of admin typically preferred for (and by) younger patients who work and travel. We have seen in some emerging markets that intravenous routes may be preferred from a psychological point of view, linked to the placebo effect – with an IV infusion, the patient feels they are taking something potent (and therefore effective), and the HCP feels like they are prescribing something strong. On the other hand, oral medications can be perceived to be trivial or inappropriate; a mentality of ‘I have cancer, not a headache’.
Another consideration that should not be overlooked is how involved the patient is in the decision. It is well documented that physicians in some markets and cultures tend to take a more paternalistic approach to patient consultations than others. In Southeast Asia, for example, communication from physician to patient tends to be more one-way than the ‘partnership’ approach promoted in many European markets. Physicians who make the decision for a patient may make different choices to patients who are presented with options by their physician and asked to choose. Prescribing physicians are often less well informed of the pros and cons relating to different forms of admin compared to the nurses, patients and/or caregivers who are directly involved in the administration. Considering the preferences of each of these stakeholders (as relevant depending on the product in question), and understanding the relative influence of each in the ultimate prescribing decision, is therefore important in establishing the optimal route of admin.
When it comes to chronic therapy, a patient’s level of attachment to a particular device or form of administration can have a major impact on product choice. If there is a risk that changes in the appearance of a patient’s medication or their device is likely to affect compliance, physicians may be reluctant to switch brands. For lung diseases such as asthma and COPD, where inhalers are the most effective way to deliver medications to the target, this is particularly relevant because success is so dependent on good technique and some inhalers may be easier for an individual patient to use than others. This means providing education is key when introducing a new or updated inhaler to the market. The same applies to other self-administered or caregiver-administered devices such as autoinjectors and blood glucose monitors. Fine-tuning the design to ensure ease and comfort of use can make the difference between success and failure. Perhaps a more subtle consideration is that if patients need to use a device in public, something that is discreet may be more acceptable – how sensitive patients are in this regard also varies across cultures and conditions. In India, for example, some asthmatic patients avoid using their inhalers in public, as it is socially stigmatized due to the association with addiction.
There may also be reimbursement or access considerations related to route of admin which can vary by market. In Russia for example, patients must pay for drugs in the out-patient setting which are provided free of charge to in-patients. This arrangement has been criticized as incentivising unnecessary hospitalisation and can lead to a preference for inconvenient IV infusions over subcutaneous products that can be administered in home. Many HCPs also prefer HCP-initiated injections because it is not possible for patients to purchase them through other channels. The patient has to return to the HCP for a repeat dose, thereby protecting their revenue stream. This can be particularly relevant where medical tourism is involved. Take for example the case of an Indonesian patient travelling to Singapore for treatment: if they are prescribed an oral treatment they can simply buy it back home in Jakarta but if they are prescribed an infusion they must return to Singapore.
Innovative technologies can also have an impact on cost and access. While the majority of vaccines are currently delivered via needle and syringe, innovative delivery technologies such as Nanopatch™, a transdermal device that perforates into the skin, are being investigated. Beyond the obvious benefits of increased acceptance among patients that are needle phobic, this is also particularly relevant for less developed countries because it has the potential to alleviate the need for a cold chain (maintaining the vaccine at a given temperature range throughout the supply chain), therefore enabling mass immunisation to be implemented more cost effectively.
In conclusion, optimising the route of admin is a fundamental step in the path to market for any pharmaceutical product. However the preferred route of admin can be influenced by individual preferences (which may vary between stakeholders), cultural considerations and healthcare system logistics and funding. This means we often encounter a discrepancy in the routes of admin that are most valued by HCPs and patients in emerging markets compared to mature markets, and the preferences can often be surprising and unpredictable: what holds true in one country or region should not be assumed to apply to another. In-depth market understanding and comprehensive testing of various route of admin options in the local context should therefore be an essential component of any emerging market launch strategy.