Trial design should be more patient-centric

There are many patient-related challenges that companies face when conducting clinical trials. Sandeep Raju, Infosys, looks at the issues and gives some steps that can be taken to get the most out of research programmes

No more than a tenth of physicians participate in trials

There are many patient-related challenges that companies face when conducting clinical trials. Sandeep Raju*, Infosys, looks at the issues and gives some steps that can be taken to get the most out of research programmes

Despite the fact that patient outcomes are critical to the success of a clinical trial, drug development organisations often under-invest in patient engagement. Sponsors, contract research organisations and healthcare professionals engaged in trials undoubtedly invest heavily in patient care; however, inefficiencies in recruitment, retention and adherence lead not only to higher costs but also to poor outcomes.

Pharmaceutical companies are having to put more resources into patient outreach and support programmes to encourage adoption, improve adherence and, eventually, minimise revenue leakage. In addition, they are being forced to change traditional practices in favour of a patient-centric approach to trial design and execution. This does warrant focused investments early in the lifecycle of a trial – but downstream benefits can be substantial.

recruitment challenges

Recruiting patients for a trial is expensive, consuming up to a third of total costs of a study. Referrals from healthcare providers remain the primary channel, but no more than a tenth of physicians care to participate in trials, with more than a third of those participating opting not to conduct a second trial. Advertising, direct mailings and web-based campaigns are increasingly used but they can only supplement traditional means of recruitment. Patient organisations are key, especially for orphan drugs and biologics.

Public perception about the industry does not help either, as two surveys by Harris Interactive reveal. In 2010,1 only 11% of respondents perceived pharmaceutical companies as honest and trustworthy, and in 2005,2 46% of respondents stated that they saw trial patients as ‘guinea pigs’. In general, awareness about success stories from clinical trials is poor.

Even among patients who are interested, tighter scientific and regulatory rigour leads to fewer being eligible: in most therapeutic areas, patients with multiple chronic conditions often don’t qualify. Among patients who are eligible, low levels of trust are commonplace owing to, as an example, informed consent documentation and processes that are jargon-heavy and therefore difficult to grasp.

It also does not help that collaboration across trial design and recruitment teams is often poor, leading to inadequate input from front-line staff into protocol design and study planning. In all, challenges in the recruitment process result in fewer sign-ups and therefore necessitate additional sites.

This is evident in the results from a study on patient participation in oncology trials,3 published 10 years ago but still very relevant today. Figure 1 illustrates the challenges typically faced by oncology teams – success ratios are usually worse for other disease areas although patient pools tend to be larger.

Figure 1: Despite sizeable investment in recruitment, downstream success ratios tend to be low

patient attrition

Following the sizeable investments made in recruitment, downstream success ratios tend to be low, as the numbers in Figure 1 indicate. A fraction of recruited patients end up providing conclusive results useful for a dossier, thanks to retention as well as adherence challenges.

Patient retention is a big issue; a 2006 FasterCures event4 interviewee suggested that around 30% of patients drop out during a trial, many for simple reasons such as excessive travel to investigator sites. However, some of the root causes discussed are telling; for instance, only a fifth of volunteer patients hear back regularly from their host sites.

In general, diligent communication to participating patients on overall trial progress and study outcomes is poor; participants often lack an understanding of how their role in a study is a significant contribution to medical research. This under-appreciation leads to missed opportunities to cultivate active advocates among the patient community.

Patient non-compliance is a well-understood challenge, having an adverse effect on health outcomes and in the long run, costs. For instance, a 2010 study in the Journal of General Internal Medicine5 estimated that more than a fifth of e-prescriptions go unfilled. A somewhat older Harris Interactive survey6 estimated that 22% of US adults did not fill their prescriptions and that many of them did not consume medication as directed.

Similar challenges are evident in drug development as well; a study by Kenneth Holroyd7 in 2005 found that up to half the patients were non-compliant with their prescribed treatments. Patient awareness and motivation are key issues, with adverse reactions, lack of therapeutic impact and behavioural or lifestyle patterns often leading to poor compliance with regimen.

unreliable measures

The lack of reliable measurement techniques compounds the challenge. A fourth of all trials use patient diaries but only a tenth or so are electronic. Pill or prescription counts help but are not reliable measures. Patient surveys may yield some insight but, to quote Hippocrates, ‘Keep watch also on the faults of the patients, which often make them lie about the taking of things prescribed’.

For patients recruited in developing countries, low education levels and local cultural factors often pose challenges. Under-informed consent, fewer investigators with heavy schedules, poor access to medical facilities and limited training for site staff are all barriers to effective patient engagement.

However, there are key steps that sponsors and their partners can take to tackle these issues:

Smarter use of IT to increase effectiveness and drive down costs

Streamlining patient engagement practices across trials and deploying a common but customisable IT platform can help scale down investment needs while providing more consistency and transparency on the effectiveness of patient engagement initiatives.

Within regulatory constraints, it is helpful to provide patients with online access to their own information and to progress updates on the overall trial. Online patient support networks, including peer-to-peer mentoring, can also be powerful mechanisms to attract and engage trial participants. For tracking consumption patterns, electronic paper diaries tend to be much more reliable than their paper counterparts. Additionally, mobile devices can be a huge asset – among other uses, automated reminders can significantly improve compliance levels.

Better protocol design and study planning

Stronger alignment between trial design and patient recruitment teams can feed back crucial front-line inputs to protocol design and study planning teams. Likewise, closed-loop feedback to the design teams from CROs and other external partners involved in recruitment can help fine-tune design and planning decisions, keeping in mind patient acceptance. In particular, unrealistic, time-consuming expectations from patients and complicated dosing are pitfalls to watch out for.

Patient-centric product design

Packaging is crucial to patient acceptance and compliance. Especially in trials, prioritising patient-friendly packaging over production efficiency is worthwhile. For instance, the use of blister packs with visual aids instead of bottles, can be a great help. The avoidance of large capsules (e.g. over-encapsulation for double-blind trials) and designing labels to better align with patient information needs can also help improve adherence.

Strong engagement during the early days

The first few weeks on a trial set the stage for how a longer-term relationship with the patient plays out. To start with, well-articulated and transparent informed consent can educate patients and help gain their trust. Moreover, investing in clinical education teams to coach patients on the disease and to help adopt their treatment regimen can help. Likewise, telephonic nursing support in the initial stages can help patients settle in and lower the chances of early dropouts.

Ongoing connect between patients and sites

State-of-the-art medical care is a key reason for patients to sign up and, importantly, stay engaged on trials. On some trials, taking the site to the patient by providing personalised at-home support can help. Direct and frequent communication between patients and sites is key – and the role of study co-ordinators in supporting this often goes under-appreciated.

The 2006 FasterCures event mentioned earlier highlighted that roughly 80% of participants in a trial are motivated by a desire to contribute to medical sciences; clearly, patients appreciate seeing the big picture.

However, patients rarely get personalised and timely communication about trial results. Regular updates on progress and high-quality newsletters relevant to their medical condition can greatly help nurture patient ambassadors and help spread the word.

Availability of multi-channel patient support

Helplines with well-qualified personnel can help patients cope with inevitable side-effects, understand complex drug delivery mechanisms, navigate complex insurance and reimbursement provisions, and, importantly, provide counselling and emotional support. Multi-channel reminders (e-mails, SMS, IVR, phone calls) for medication, physician appointments, as well as record-keeping can all contribute to strengthening adherence.

Clinical trials form the backbone of pharmaceutical research and despite the huge financial investments that are made each year, there is still more that can be done to get better results from fewer patients. Ultimately, a greater focus on patients is needed to help strengthen recruitment, retention and adherence to clinical trials. Patient-centricity may warrant additional funding to start with. However, the long-term benefits of fewer drop-outs, more meaningful results and lower overall costs justify the short term investment for the long-term gains.

references

1. Harris Poll, December 2010

2. Harris Interactive Healthcare News, June 2005

3. Journal of Clinical Oncology, 2001, 19(6) pp 1728-1733

4. FasterCures meeting ‘Clinical Trials Recruitment and Retention: Best Practices and Promising Approaches’, Sep 2006, Ken Getz interview

5. M.A. Fischer et al. Journal of General Internal Medicine, 2010, 25(4)

6. Harris Interactive Healthcare News, Nov. 2001

Sandeep Raju is a client services leader with the Life Sciences practice at Infosys

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