Medical research has undoubtedly contributed to better quality of life and increased longevity. Nevertheless, we have illustrated in this book how the existing ‘drivers’ for research – commercial and academic – have not done enough to identify and address patients’ priorities.

Huge sums of money – over $100 billion every year worldwide – are spent on funding medical research.¹ However, most of this funding is invested in laboratory and animal studies, rather than in studies that are likely to produce evidence more immediately relevant to patients.

Even when it comes to deciding which questions about the effects of treatments will be studied, patients’ priorities are widely ignored. The drug industry’s financial power means it is very influential in decisions about what gets researched. Because industry can pay handsomely (thousands of pounds/dollars) for each patient recruited to its clinical trials, academics – and the institutions they work in – too often take part in clinical trials that address questions of interest to industry rather than to patients.

Regrettably, much of the money spent on medical research is wasted at successive stages – by asking the wrong research questions; by doing studies that are unnecessary or poorly designed; by failing to publish and make accessible the research results in full; and by producing biased and unhelpful research reports. This should matter to everyone – researchers, research funders, clinicians, tax payers, and above all patients.

Before setting out our blueprint for a better future, we briefly outline why, if research is to be better, it is vitally important to:

1. Ask the right research questions
2. Design and conduct research properly
3. Publish all the results and make them accessible
4. Produce unbiased and useful research reports

How the money spent on medical research is wasted at successive stages.¹

1. Ask the right research questions
   Sometimes doctors do not know which treatment is likely to be best for their patients because the available options have not been properly studied. Such studies, which can have important implications for patient care, may be of little or no interest to industry or academia so important questions remain unanswered. And not answering these questions can lead to immense harm. Take one example – whether steroid drugs given to people with brain damage as a result of physical injury increase or decrease their chances of survival. Steroids were used for decades before a well-designed study showed that this established treatment had probably been killing thousands of patients with brain injury.² Proposals for this study were initially opposed by industry and some university researchers. Why? They were engaged in commercial trials assessing the effects of expensive new drugs (so-called neuroprotective agents) on outcome measures of questionable importance to patients, and they did not wish to face competition for participants.
   Another reason for tackling these unanswered questions is to help ensure that the precious resources available for healthcare are not being wasted. When human albumin solution, given as an intravenous drip, was introduced during the 1940s to resuscitate burned and other critically ill patients, theory suggested that it should reduce their chances of dying. Amazingly, this theory was not subjected to fair tests until the 1990s. At that point, a systematic review of the relevant randomized trials could find no evidence that human albumin solution reduced the risk of death compared with simple salt solutions. What the systematic review showed, in fact, was that if albumin had any effect on death risk it was to increase it.³ The findings in this review prompted doctors in Australia and New Zealand to get together to do the first sufficiently large fair comparison of human albumin solution with saline (salt water), an alternative resuscitation fluid.⁴ This study – which should have been done half a century earlier – could find no evidence that albumin was better than salt water. Since albumin is about 20 times more expensive than saline, huge sums of money from healthcare budgets worldwide must have been wasted over the past 50 years or so.
2. Design and conduct research properly
   Stimulated by surveys revealing the poor quality of many reports of clinical trials, reporting standards have been developed and applied. Such standards make clear how many patients have been asked to participate in a study and how many declined the invitation. Results are presented according to the various treatment groups selected at the outset. But there is still a long way to go to improve: (a) the choice of questions being addressed in research; (b) the way that these questions are formulated to ensure that the outcomes of treatments chosen for assessment are those that patients regard as important; and (c) the information made available to patients. (See Chapters 11 and 12.)
   To see whether a proposed trial might be feasible and acceptable, exploratory work involving groups of patients can be useful. This may highlight shortcomings in the design plans; or help to define outcomes that are more relevant; or even suggest that the concept is a non-starter.^{5, 6}
   This can save a lot of time, money, and frustration. The clinical trial in men with localized prostate cancer that we described in Chapter 11 (p140–141) showed how the research design was improved by careful consideration of the terms used by clinicians to describe the trial’s purpose and the treatment options. Exploration of patients’ views led to an acceptable study because the concerns and information needs of the men being invited to participate had been identified, and the information provided to potential participants took account of these findings.⁷
3. Publish all the results and make them accessible
   Selective reporting of the results of research can lead to serious biases. Some ‘negative’ studies are never published when the results do not match the expectations of the investigators or funders. Without a published report to tell the tale, these trials disappear without trace.⁸ Furthermore, results within published trials may be selectively reported – that is, some of the results are excluded because they are not so ‘positive’ for the treatment being tested.⁹ Patients have suffered and died because of biased reporting of research on the effects of treatments. This practice is unethical as well as unscientific.
4. Produce unbiased and useful research reports
   Even when studies are published, they often omit important elements that enable readers to assess and apply the findings. One review of 519 randomized trials published in reputable journals during December 2000 found that 82% did not describe the process of allocation concealment and 52% did not provide details of measures to reduce observer biases – both features that we suggested in Chapter 6 were crucial to good studies.¹⁰ This poor reporting of details extends even to the description of the treatments used. A trial showing that giving a specific booklet (compared with no booklet) helped patients with irritable bowel syndrome, omitted to describe the contents of the booklet or how to obtain it; the ‘treatment’ could therefore not be used by any other patients or doctors. This was just one example in an analysis of trials in major journals that found about a third omit such crucial details.¹¹
   Finally, most published trials do not set their results in the context of previous similar trials. Without this key step, as we explained in Chapter 8, it is impossible to know what the results actually mean. Four-yearly checks of randomized trials reported in five major medical journals over a period of 12 years – 1997–2009 – illustrate the extent of the problem. Overall, only 25 of 94 (27%) reports made any reference at all to systematic reviews of similar trials. Only 3 of 94 reports actually contained updated reviews integrating the new results, and so showing what difference the new results had made to the totality of evidence. Sadly, there was no evidence of improvement in reporting practice with the passage of time.¹² This failure can lead to clinicians using different treatments depending on which journals they happen to read.