Clinical trials and their patients: The rising costs and how to stem the loss

pharmafile | November 3, 2016 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing |  clinical trials 

The pharmaceutical industry has a big problem and it’s one that keeps getting worse every year – how to stop clinical trials haemorrhaging money. A major contributor to costs is patient recruitment and then retention within the trials. Originally published in the November issue of Pharmafocus, Ben Hargreaves takes a look at why these losses occur and the possibility of finding a solution.

Clinical trials are where the long work of producing a drug with the potential to cure illnesses and diseases should come to fruition. It should represent the end of an intense period of activity with either the reward of positive results or the possibility of the effort put into the drug coming to nothing. What often happens, when drugs attempt to go clinical trials, is an incredibly difficult and slow process. The difficulties faced in getting patients to enrol on clinical trials are challenging enough and thereafter emerge the issues regarding ensuring that patients continue with the trial.

When discussing clinical trials, it is certain that the costs of the trials will be at the forefront of any discussion. The figures speak for themselves, with astronomical rises in costs in the space of the last decade. In the US, the average cost per patient, between the years 2008-2013, had increased by 157%, according to Medrio data. Whilst in the UK, between the years 2008-2011, costs per patient rose 88%, as reported by Cutting Edge Information. A large part of this cost can be placed upon the active recruitment of enough patients and then the potential cost of clinical trial failure to complete.

The problems faced in patient recruitment and retention

The challenge of recruiting enough patients is a huge part of the problem. Many trials struggle to acquire the requisite number of patients to begin the trials. The figures speak for themselves with 50% of trials delayed due to patient recruitment issues while some trials struggle to find any patients to begin the trial at all, incurring a massive cost with no potential to recoup this loss with a successful trial.

Once patients have been recruited, this is by no means the end of the battle. 30% of patients who have been successfully recruited then fall away as the trial progresses. Beyond this is the fact that 85% of clinical trials, according to Forte research, fail to retain enough patients to continue.

All of these recruitment and retention problems have the knock on effect of massive delays to trials, with only six percent of clinical trials completed on time, and 80% of trials are delayed by at least one month. These delays affect not just study costs but subsequent sales, causing potential losses of $600,000 to as high as $8 million per day, according to a CenterWatch study. Speaking to Pharmafocus, Alun Pinnegar, senior clinical operations manager and country head, UK & Ireland, at AbbVie, stated simply that “The biggest contributor to rising costs is the time it takes to complete our trials – the longer the trial, the higher the cost.” This is a view repeated when we spoke to Dr Doug Brown, head of research and development at Alzheimer’s Society, he said: ““Clinical trials for all health conditions and diseases are not cheap to run – staffing, running the facilities, and the nature of the clinical procedure itself all add to the cost. For Alzheimer’s disease trials, recruitment is a significant cost factor.”

With the costs being so high, so much money being potentially lost and so much time spent in the process of clinical trial recruitment, there are huge gains to be made by improving the rate of recruitment and retention, even if only by a small amount. The industry has begun to recognise that there is an issue, pouring an increasing amount of money into the process but seeing results plateau. TUFTS Center for the Study of Drug Development concluded that total capitalised cost per approved new compounded grew at an 8.5% compound annual rate whilst rates of drug approval, in relation to cost, dropped significantly. If increased funding is not the answer to the process, there has to be an examination of other solutions.

Educating the wider public

One of the largest and long-standing problems faced by patient recruitment is the extent to which the general public are educated about clinical trials. Going back to 2001, the Will and Why survey, commissioned by Harris Interactive in a BBK Healthcare Poll of 5000 US citizens, found that 81% of respondents were not aware of safeguards such as the Declaration of Helsinki, The Belmont Report, Institutional Review Board, and the informed consent process. Subsequently, in 2004, a similar European poll was conducted by BBK Healthcare, that found 71% were also not aware of measures taken to protect patients. Both polls indicated an increased willingness to participate in clinical trials if they were made aware of the measures.

This last point is key – the more potential clinical trial patients know about the process, the more indication they give that they are willing to sign up to the process. Ethically, there is a barrier between directly encouraging a patient to commit to a clinical trial therefore the emphasis should be on education and not persuasion. This education does not necessarily need to be in such great detail either, basic information has been shown to increase the likelihood of participation. For example, in the same Harris Interactive study, 85% of patients were either unaware or unsure that participation in a clinical trial was an option at the time of diagnosis. After being made aware, 75% indicated a willingness to participate. This is backed up by the research that AbbVie has conducted into the issues that clinical trials face to recruitment. Alun Pinnegar told us that “there is often a lack of knowledge about what a trial is and what it isn’t and we need to do significantly more education with diagnosing doctors and the general public to make clinical trials a more frequent option.”

The importance placed on diagnosing doctors cannot be stressed enough. As they are at the front line of care and are trusted to provide the best care possible, which clinical trials often represent. A poll commissioned by Research!America  found that 72% of patients would be likely to participate in clinical trials if they were recommended to by their doctor. Contradicting this information is the fact that people answering this question were also asked where they found out about clinical trials, with only 24% suggesting they had heard of them from their doctor.

This emphasises the fact that one of the important factors in seeing patient recruitment figures rise and the numbers of clinical trials failures begin to drop can be achieved through a simple measure – greater communication between doctors and pharmaceutical industry regarding clinical trials. Of course, greater links between doctors and the industry can often raise eyebrows but when the basis is education and promoting potentially beneficial treatments to patients, there can be few arguments.

Wider than this, a general attempt by the pharmaceutical industry to reach out and educate as many people as possible, by casting a broad net, would also have to be high on the list of priorities. Novartis raised an issue with recruitment that perhaps, especially in our position, can be overlooked and emphasises the importance of the tool of communication. Helen Townsend, Novartis international clinical research organisation manager, UK & ROI, highlighted how “media reporting around earlier stage studies which have not been optimally managed can create a sense of fear and hesitation. People are mindful about possible side effects or the potential of being randomised to a less effective treatment arm.”

The most immediate example of bad press for clinical trials came after the infamous ‘elephant men’ trial, conducted by Parexel. The trial was testing an immunomodulatory drug known as TGN1412, developed by TeGenero (who went bankrupt shortly after) in a Phase I trial, the first to be conducted on humans. The study left six men in critical condition, with one close to death. They became known as the ‘elephant men’ after a girlfriend referred to them with the moniker. The story spread like wildfire and will still resurface from time to time as the anniversary and compensation stories arise. It is a story that had huge negative impact upon the perception of clinical trials, with the story spreading quickly through the UK to worldwide news outlets.

In reality, the catastrophe of this particular clinical trial can be pinned down to bad practise. It is not indicative of the wider practise of running clinical trials yet it will be the one that sticks in peoples’ minds. In many ways, the quiet successes of clinical trials within the pharmaceutical industry will allow the memory of this particular incident to fade but there is a distrust that has developed from this particular instance. Dr Cham Herath, a medical director at Chiesi Pharmaceutical, who has had years of experience working on clinical trials, spoke to Pharmafocus about educating the public on clinical trials. “The general public’s understanding of clinical trials is poor; however most are open to participating once they understand what they are being asked to do but less likely if they know it’s a pharmaceutical company sponsored study.”

He continued, “This inherent distrust of the industry was borne out by research conducted by the NHS Health Research Authority in 2013. Hence we need to educate the public about the industries involvement in clinical research and that all research is governed by the same regulations. Many people are probably unaware that the vast majority of studies on EudraCT at any given time are pharmaceutical sponsored (~70%).”

 Gaining the public’s trust is a slow process and being more proactive in communicating regarding the safety, efficacy and benefits of clinical trials may do more to wipe this particular bad memory from the public conscious. Especially when recruiting people is not the only challenge, it’s getting them to stay within the trial once they’ve begun.

Once they begin the study, what makes the patients leave?

Patient retention is a much bigger issue than would be considered, at first glance. Why wouldn’t patients choose to stay with the program and treatment they had made the effort to join? The answers range from the serious to the trivial. Patient dropout rates range from 15-40%, according to a 2007 Business Insider report. The fallout of patients dropping out of studies is the increase in cost, time spent on performing recruitment and the potential failure of the trial to be completed successfully.

Alun Pinnegar, of AbbVie, admitted that “all clinical trials require a significant commitment from patients, normally beyond standard of care visit requirements. This might be in the form of additional visits, additional procedures and certainly a substantial additional time commitment. As many areas of research engage patients who have work and family commitments, the time demand of a trial can often lead to a reappraisal of participation part way through, even if enthusiastic to start with.”

He continued, “It is imperative that patients are fully informed upfront, not only on the potential benefits and risks of participation but also clarity on the commitment and time required to complete all the clinic visits required in the study. “

There are always going to be problems that any amount of consultation and feedback will not be able to fix; it will always be highly nigh on impossible that a trial will retain a 100% patient roster from beginning to end of the trial. There are fixed obstacles that will always be difficult to overcome – if the drug given is showing little sign of efficacy or the patient moves away from the area, the patient may not be inclined to stay on with the study.

There are, however, a number of smaller reasons that patients tend to leave trials that crop up recurrently. If these issues can be addressed then the figure of 85% of clinical trials failing to retain enough patients can be reduced and thereby reduce the vast sums of money that are lost in the process. Forte research found that some of the common reasons given for dropping out of the study were: forgetting visits, financial constraints, lack of appreciation, fear and anxiety, condition not improving and misunderstood expectations.

The movement towards ‘patient centricity’

The common link between all of these listed reasons is that they are all manageable by interaction with patients. The buzzword that has circulated throughout the industry in the last few years, when it comes to greater emphasis being placed on patient communication and comfort, is ‘patient centricity’. It’s a contested term as to its actual application but it has come to mean whatever method successfully involves the patient to a greater extent within the trial and making the patient feel part of the success of the trial.

Helen Townsend, of Novartis, identifies what their findings have been from trying to improve patient retention: “For all studies, the most important factor in ensuring patient retention is the site staff and their attitude towards the study. It is also about effective communication, being transparent with the likely time commitment required and the potential benefits to the patient. Nowadays, we are exploring the use of new technologies to assist with retention; sending text messages to patients to remind them about clinic visits, for example. We do also send birthday cards, Christmas cards and calendars for one of our long term outcomes studies.”

The common thread between these means of improving retention is the ‘patient centric’ approach – whereby the patient is catered to and treated like an individual human being, as opposed to a number within a trial. The methods that Novartis have used, in sending out cards at important dates, text messages and ensuring site staff are a welcoming presence at the site, all point towards this method – opening up further lines of communication with patients and interacting with them as colleagues, as opposed to subjects.

There is now a growing advocacy to have patient consultation groups to increase communication with pharmaceutical companies from Phase 0 onwards. The point being to identify what treatment the patients want for their particular symptoms, with the most obvious not always being the most important. When communication lines were opened up to Parkinson sufferers, many suggested that the pronounced physical symptom of shaking was not as important to them as treatment aiding them to sleep at night. During the process, there has developed a greater focus on keeping in contact with patient, with methods mentioned previously. After the clinical trial process, informing the patients to let them know the results of the trial and to acknowledge them as valued partner in the trial has also been developed. Alun Pinnegar, of AbbVie, mentioned that they now send “patient friendly” summaries of the result of the trial – making them feel more included in the results of the trial and their contribution valued.

The refrain to improving both patient recruitment and retention can be clearly seen to revolve around communication. The aim of fostering strong links between pharmaceutical companies, their trials and the potential patients is obviously a concerted goal for all involved in the process. The question, of course, is how can this aim be achieved and how can numbers recruited and retained be increased? This is where the second part of the feature will move onto, looking at the ways the rise of social media and smartphone apps can play its part in opening up new lines of communication and strengthening those that already exist.

Ben Hargreaves

Continue reading Part Two here.