Kamal R Mahtani: Using systematic reviews to reduce research waste—who really cares?

The global spend on biomedical research and development is estimated to be about $250 billion (£203 bn; €233 bn) each year—a not insignificant figure. In fact, it roughly equates to the amount that the UK government spends each year on its combined education, defence, and welfare budget.

Kamal R Mahtani

But suppose you heard that the UK government’s budget for education, defence, and welfare was being wasted and provided no public benefit at all—what would your reaction be? Surprise? Indignation? Anger?

Chalmers and Glasziou’s revelation that about 85% of biomedical research may be wasted should evoke at least as great an outraged response. This estimate of wastage is derived from a number of factors—including failure to conduct, describe, and publish research to standards that make the outputs useful. This is particularly concerning, given that much of this research is expected to provide some form of patient benefit.

Among the proposed steps to reduce this waste is a recommendation that new research should not be conducted until a systematic assessment of existing research has been performed. There are at least two reasons why this makes total sense. Why would you want to conduct a new study if the answer was already available? And, more importantly, if the answer was available already, would it even be ethical to enter participants into a new study when some might fare worse?

Some public funders of research, such as the UK’s National Institute for Health Research (NIHR), which manages an annual budget of about £1 billion for applied research, recognise the importance of systematic reviews in reducing research waste. As one example of this, new applicants seeking funding from the NIHR to support primary research must now ensure that their request is informed by knowledge of the existing evidence.

But what about other funders? The aim of a recent survey of the websites of 11 international research funding organisations was “to indicate the extent to which each organisation adopted waste reducing policies and processes.” The authors extracted information on whether the funder involved members of the public in setting research priorities; made full protocols for funded research publicly accessible; and had specific funding streams for methods research. The survey also identified information about how the funders supported the conduct of systematic reviews.

Although the authors reported that they used their judgment in the interpretation of their findings, they do also report that they checked the accuracy of their findings with each organisation. According to their survey results, only two of the funders, the NIHR and the Canadian Institutes of Health Research, had clearly dedicated streams to fund systematic reviews. The survey also concluded that only one funder, the NIHR, made it a prerequisite that all applications for support should be informed by a systematic review of the existing evidence.

Scientific, ethical, and economic reasons make it essential to conduct a systematic review of existing evidence before considering a new study. Failure to do this is simply poor practice. This recent survey shows that there is still work to be done to ensure that this principle is clearly and demonstrably supported. Given their large budgets and major influence on what does and does not get financial support, funding agencies have a particular responsibility to lead this initiative.

Kamal R Mahtani is an NHS GP and deputy director of the Centre for Evidence Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford.

Source: BMJ

New Recommendations for Hypertension Management Released.

New recommendations published online in the Journal of the American Medical AssociationExternal Link aim to provide guidance on the management of patients with hypertension. More specifically, the recommendations focus on when medication should be started in patients, the best choices for medications to begin treatment; and communicating achievable blood pressure goals to patients.

“Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults,” the report authors note.

The report, written by panel members appointed to the Eighth Joint National Committee, notes there is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg. However, given insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, the panel recommends a BP of less than 140/90 mm Hg for those groups. “The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years,” the report notes.

In general, the report authors note that the 140/90 mm Hg definition from Joint National Committee 7 “remains reasonable” and recommend that lifestyle interventions be used for everyone with blood pressures in this range. “For all persons with hypertension, the potential benefits of a healthy diet, weight control, and regular exercise cannot be overemphasized,” they said. “These lifestyle treatments have the potential to improve BP control and even reduce medication needs.”

Also in the report, the authors note there is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. Additionally, there is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes.

Moving forward, the authors point out that an algorithm included as part of the recommendations will facilitate implementation and be useful to busy clinicians. They also suggest that “the strong evidence base of this report be used to inform quality measures for the treatment of patients with hypertension.”

Practice guidelines are traditionally promulgated by the government or by learned medical professional societies. The JAMA paper is a report of a group experts in the field of hypertension, but it does not carry the endorsement of any organized body. Moving forward, these recommendations will be taken into account in the coming year as the ACC/AHA Task Force on Practice Guidelines moves forward with developing the collaborative model to update the national hypertension guidelines in partnership with the National Heart, Lung, and Blood Institute (NHLBI). According to the ACC and the American Heart Association (AHA), once a writing group is appointed, there will be an extensive science and evidence review process, followed by draft recommendations that will undergo a peer and stakeholder review. Once the review process is complete, the ACC/AHA and partnering organizations will publish the guidelines in 2015 for clinicians to follow as the national standard for hypertension prevention and treatment.

The ACC, AHA and the Centers for Disease Control and Prevention released a scientific advisory on the effective approach to hypertension in November that encourages use of enhanced, evidence-based, blood pressure treatment systems for providers, including standardization of protocols and algorithms, incentives for improved performance based on achieving and maintaining patients at blood pressure goals, and technology-facilitated clinical decision support and feedback.

Aiming for a Better Understanding and Management of Cancer-Related Fatigue.

Cancer-related fatigue (CRF) is a serious symptom of patients with cancer and deteriorates their daily quality of life. Whereas fatigue is a common problem in the general population, with a prevalence of about 30%, up to 99% of patients with cancer have fatigue of more intense severity. CRF is directly related to the biology of cancer, but it can also be caused by anticancer treatment. We reviewed current evidence about the potential pathophysiological mechanisms causing CRF. Clinical methods to determine the presence and severity of CRF and potential treatment options to reduce CRF will be discussed. After reading this review, the reader will have knowledge of the current understanding of CRF and will be able to give evidence-based advice to patients with CRF.


Source: The Oncologist.

Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment elevation myocardial infarction with or without angiography: a secondary, prespecified analysis of the TRILOGY ACS trial .

Wiviott SD et al. – Treatment with prasugrel and aspirin improves outcomes compared with clopidogrel and aspirin for patients with acute coronary syndrome who have had angiography and percutaneous coronary intervention; however, no clear benefit has been shown for patients managed first with drugs only. Authors assessed outcomes from the TRILOGY ACS trial based on whether or not patients had coronary angiography before treatment was chosen. Among patients who had angiography who took prasugrel there were fewer cardiovascular deaths, myocardial infarctions, or strokes than in those who took clopidogrel. This result needs to be corroborated, but it is consistent with previous trials of more versus less intensive antiplatelet treatment. When angiography is done for acute coronary syndrome and anatomic coronary disease confirmed, the benefits and risks of intensive antiplatelet treatment exist whether the patient is treated with drugs or percutaneous coronary intervention.


  • TRILOGY ACS (ClinicalTrials.gov number NCT00699998) was a randomised controlled trial, done at more than 800 sites worldwide.
  • Patients with non–ST–elevation acute coronary syndrome who were selected for management with revascularisation were randomly assigned to clopidogrel or prasugrel.
  • The primary endpoint was cardiovascular death, myocardial infarction, or stroke at 30 months.
  • In the present analysis we assessed differences in the primary endpoint by angiography status and whether the effects of treatment on the primary endpoint differed between patients who had angiography before enrolment and those who had not.


  • 7243 patients younger than 75 years were included in the TRILOGY ACS primary analysis.
  • 3085 (43%) had angiography at baseline, 4158 (57%) had not.
  • Fewer patients who had angiography reached the primary endpoint at 30 months compared with those who did not have angiography, according to Kaplan–Meier analysis (281/3085 [12•8%] vs 480/4158 [16•5%], adjusted hazard ratio [HR] 0•63, 95% CI 0•53—0•75; p<0•0001).
  • The proportion of patients who reached the primary endpoint was lower in the prasugrel group than in the clopidogrel group for those who had angiography (122/1524 [10•7%] vs 159/1561 [14•9%], HR 0•77, 95% CI 0•61—0•98; p=0•032) but did not differ between groups in patients who did not have angiography (242/2096 [16•3%] vs 238/2062 [16•7%], HR 1•01, 0•84—1•20; p=0•94; pinteraction=0•08).
  • Overall, TIMI major bleeding and GUSTO severe bleeding were rare.
  • Bleeding outcomes tended to be higher with prasugrel but did not differ significantly between treatment groups in either angiography cohort.

Source: Lancet

Patient information leaflets: “a stupid system”.

The NHS’s multifarious patient information leaflets are inaccurate, inconsistent, and confusing, finds Margaret McCartney, and effort is duplicated because each trust commissions its own, often from the private sector

The so called patient revolution is nothing without quality information. And so the NHS is awash with patient information, especially leaflets, in hospital wards, outpatient clinics, and general practitioners’ surgeries. Some trusts commission leaflets from external, profit making companies; others write their own. But how efficiently does the health service coordinate them, and are leaflets tested for effectiveness on patients?

In a recent study researchers asked 128 trusts for leaflets given to patients after an inguinal hernia repair, and 93 trusts responded.1 Almost one in five trusts sent a leaflet created by a private company, Eido Healthcare. Others had inconsistent guidance on when to return to office work (ranging 1-6 weeks) or manual work (2-12 weeks). Similarly, leaflets gave conflicting advice about when to resume driving, sex, and sport. This means that patients are being given very different information about the effects of the same surgery, depending on where they live and which leaflets are used.

A similar study examined leaflets provided to patients who had been offered extracorporeal shockwave lithotripsy. The researchers found that the leaflets did not consistently mention common recognised complications and some were not mentioned at all.2 Another study, which examined patient information leaflets given for transrectal ultrasound guided prostate biopsy, again found wide variation, with drugs, analgesia, and complications often inadequately explained.3

“It’s a stupid system, a waste of money, and, without rigorous standards of searching and appraisal, much of the information is biased and misleading—especially in terms of fair representations of risk,” Muir Gray told the BMJ, reflecting on the current situation in the NHS. Gray is co-chair of the executive council of the Information Standard, an independent certification scheme funded by the Department of Health for organisations producing evidence based healthcare information for the public.

Gray said that a lack of coordination and slow uptake of the certification scheme by the NHS has meant that much information provided to patients is of poor quality. “Patients have a right to clean, unbiased information, but they can’t get that off the internet,” he said. “It’s not possible to communicate to a patient in 10 or 20 minutes everything about a decision. Knowledge is essential, but you can’t rely on the consultation—you don’t have the time. Therefore we need to supplement and complement face to face. You need that to help people reflect on their values, to discuss their fears and anxieties.”

The Information Standard, which is run by the for profit company Capita, offers a kitemark if the information presented is evidence based, clear, and accurate. Patients should also be involved and have tested the information.

Some 400 UK hospitals use Eido, a private company, to produce information leaflets for them. Eido’s website says that the company produces “informed consent patient information leaflets,” which it says “improve the doctor-patient relationship, reduce the risk of litigation and increase patient satisfaction.” They advertise both their Information Standard accreditation and ability to customise information locally.

Simon Parsons, a consultant surgeon in Nottingham, set up the company when he was a surgical registrar out of concern that the informed consent process, which was subject to then new General Medical Council guidance, was using poor quality patient information leaflets. Eido’s information leaflets are indemnified, and Parsons said, “In the 10 years we have supplied in the UK, not a single claim has been brought against us in terms of inaccurate patient information.” The company supplied audit data in support of its claim of patient satisfaction. The leaflets are not publicly available except through a hospital or surgeon who has access to them. East Cheshire NHS Trust makes one payment a year to Eido, which was for £6511 in 2012, the trust said in response to a request under the Freedom of Information Act.

Meanwhile, Guy’s and St Thomas’ NHS Foundation Trust has an online, freely available library of about 850 patient information leaflets, regularly updated, but all are produced in house.4 These are written by clinicians and healthcare professionals, and tested by patients or lay readers to ensure they can be easily understood. Anita Knowles, director of communications, told the BMJ that the trust ensures leaflets are necessary and would not duplicate a good leaflet from elsewhere. The patient publications team is made up of two staff team who call on additional resources as needed. They made a decision not to use external agencies because “it was just as cheap to do it ourselves. We wanted the control, as well as the ability to change information rapidly,” Knowles told the BMJ.

The problem of varying quality of leaflets is not new; in 1998 the BMJ published an investigation into the quality of leaflets on asthma given out by general practitioners. It found inaccuracies and outdated information from the NHS, drug companies, and charities.5 In an accompanying editorial, Angela Coulter, now a researcher at the University of Oxford, called for a national strategy.6

She told the BMJ that “progress has been slow.” The problem is that “the NHS still fails to take this seriously.” For example, printable patient information leaflets are available as part of the Emis computer system used by general practitioners, which are Information Standard accredited but which come with advertisements attached.

“In the patient’s eye, that can devalue it,” Coulter said. “At the moment, in most NHS trusts, there is no one who has responsibility, or, if they are junior, often they have no budget. Often leaflets are written with the best of intentions in someone’s free time, but they can end up amateurish, with the evidence and uncertainties not expressed clearly. Yet there has been so much work internationally into setting standards,” such as the Delphi method, a structured communication technique.

A spokesman told the BMJ that NHS England is launching a “major project” in September to standardise all information going out to patients, which will then go to the Information Standards Board for Health and Social Care for approval.7 One of the aims of this board, which works throughout the NHS, is to reduce inefficiencies through reducing replication. A spokesman said that there needed to be “clinically endorsed, consistent information available across the country,” which would “lead on the standardisation of all information going out to patients.”

The internet has given us a great gift of instant information sharing. The challenge now, Coulter emphasised, is to adopt high standards, updating information regularly, and making it easily accessible. The size of the NHS makes this hard to do, but it is wasteful to franchise out the core role of information provision to the private sector because each trust is paying again for the same information over and over. This is one area of the NHS where efficiency savings look ripe for the picking.

Source: BMJ



Doctors and pharma in China.

Doctor—patient relationships in China are in crisis. Doctors have been injured or even killed by patients at work. One of the major drivers might be the unhealthy and unethical relations between many doctors and some drug companies.


On July 8, GlaxoSmithKline (GSK) said that they were investigating allegations that its staff had improperly used cash and other incentives to encourage the prescription of onabotulinumtoxin A (Botox) in China. The company added that “inquiries to date have found no evidence of bribery or corruption in relation to our sales and marketing of therapeutic Botox in China.”

The Lancet has no evidence to suggest that the allegations against GSK in China are true. However, some observers claim that bribing doctors to boost drug prescriptions by some drug companies is an open secret, and that this alleged practice has compromised the public’s trust in doctors. The varieties of unethical relationships that exist between some doctors and some of the drug companies in China are said to range from cash kickbacks, lavish gifts or entertainment, ghost writing services, sponsored supplements in journals, and all-expenses-paid trips. There is real concern that doctors’ prescriptions are therefore not based solely on patient need and clinical evidence, but may be biased by commercial interests.

The perceived unethical association between physicians and industry in China is worrying, because it inevitably harms patients as well as doctors. It damages the doctor—patient relationship and, ultimately, China’s whole health system. The GSK China allegations, although unproven, have clearly rung an alarm bell for China’s regulatory authorities to ensure the drug industry promotes products in a responsible, ethical, and professional way. Chinese doctors should rely on evidence-based clinical guidelines to inform their practice, and are in urgent need of guidance on their collaborations with the drug industry in various areas such as patient care, professional education, and research. Furthermore, training for doctors in China on managing their relationships ethically with the drug industry and other organisations should start at medical school and be part of continuing professional education.

Source: Lancet

No magic answer for Achilles tendinopathy.

Although they are trendy money spinners, best evidence shows little effectiveness”—An attention grabbing subheading to an editorial by Nic Maffulli in the BMJ commenting on an intriguing randomised controlled trial (RCT) from New Zealand on the use of autologus blood injections in treating Achilles tendinopathy. It doesn’t work.

Evidence based sports medicine was radical new thinking when Tom Best and I first began to think about it. Care of the athlete had evolved empirically. Few asked questions. For example, when our university research group first began to study ice, perhaps the most commonly used treatment in soft tissue injury, there was little quality evidence to inform treatment; the duration of each application, over what period of time, the temperature of the ice (melting iced water is 0 degrees Celcius),  if it mattered if you were fat or thin etc. Clinicians then began to ask about the evidence for the tests used in clinical examination, the effectiveness of prevention, the appropriate management of common conditions. Where we thought there was certainty, there was little evidence. This RCT on Achilles tendinopathy is an important trial because it asked serious questions about a treatment that had become commonplace yet seemingly evidence free.

Much of what we think is fact in sport is hype, based often on weak science, but mostly on extrapolation from observation. People in sport are forever looking for that extra added magic ingredient to set them apart. Complicit and gullible because they want to believe.  They follow the training programme, wear the headband, chase the logo the champions wear. It is no surprise that they take the drink, buy the supplement, wear the shoe, or do the exercise endorsed by champions. Ever susceptible, suggestible—looking for an easy way, its human nature.  So, it was no surprise to see the hype surrounding yet another product on the margin. This was the next big thing—an injection to cure one of the most common and troublesome injuries.

Its great to see good quality research and more is needed. But, research is expensive and its almost impossible to justify research in sports medicine when competing for funds with cancer, cardiology, and other core medical topics.  There is an evidence vacuum and in sports medicine there is huge pressure to do something. And, always someone looking for the magic answer.

Sourc: BMJ



USPSTF Draft Recommendation: Clinicians Should Screen Adults for Alcohol Misuse, Provide Behavioral Counseling.

Primary care clinicians should screen adults for risky drinking behaviors and offer brief behavioral counseling interventions to those who screen positive (grade B recommendation), according to a draft recommendation statement published by the U.S. Preventive Services Task Force.

With respect to hazardous drinking in adolescents, the task force says the evidence to weigh the risks and benefits of screening and counseling is insufficient (grade I). Both recommendations reaffirm the group’s last guidance on the topic, published in 2004.

A USPSTF evidence review supporting the draft statement appears in the Annals of Internal Medicine. The review points out that counseling can reduce, among adults, both the number of weekly drinks and the number of heavy-drinking episodes. In clinical trials, such counseling generally involved multiple, brief contacts with primary care clinicians. Of note, the trials usually excluded individuals with alcohol dependence, so the evidence is limited to those with drinking behaviors characterized as “risky” or “hazardous.”

Source: Annals of Internal Medicine article

Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring.

Evidence-based guidelines recommend intracranial pressure (ICP) monitoring for patients with severe traumatic brain injury (TBI), but there is limited evidence that monitoring and treating intracranial hypertension reduces mortality. This study uses a large, prospectively collected database to examine the effect on 2-week mortality of ICP reduction therapies administered to patients with severe TBI treated either with or without an ICP monitor.


From a population of 2134 patients with severe TBI (Glasgow Coma Scale [GCS] Score <9), 1446 patients were treated with ICP-lowering therapies. Of those, 1202 had an ICP monitor inserted and 244 were treated without monitoring. Patients were admitted to one of 20 Level I and two Level II trauma centers, part of a New York State quality improvement program administered by the Brain Trauma Foundation between 2000 and 2009. This database also contains information on known independent early prognostic indicators of mortality, including age, admission GCS score, pupillary status, CT scanning findings, and hypotension.


Age, initial GCS score, hypotension, and CT scan findings were associated with 2-week mortality. In addition, patients of all ages treated with an ICP monitor in place had lower mortality at 2 weeks (p = 0.02) than those treated without an ICP monitor, after adjusting for parameters that independently affect mortality.


In patients with severe TBI treated for intracranial hypertension, the use of an ICP monitor is associated with significantly lower mortality when compared with patients treated without an ICP monitor. Based on these findings, the authors conclude that ICP-directed therapy in patients with severe TBI should be guided by ICP monitoring.

Source: Journal of Neurosurgery.