Major pharmaceutical companies and medical journals have agreed on 10 steps to improve the credibility of industry-sponsored clinical research.

The recommendations, developed by the Medical Publishing Insights and Practices (MPIP) group, are intended to address concerns about hidden conflicts of interest, ghost-writing and cherry-picking of positive data.

Published in the Mayo Clinic Proceedings, the 10 steps aim to improve transparency in the reporting of trial data, experimental and statistical protocols, adverse events and the professional interests of researchers.

The MPIP initiative was developed with input from GSK, Amgen, AstraZeneca and Sanofi, and is supported by six other major pharma companies.

Journals involved in the discussions included the New England Journal of Medicine and The Lancet.

The 10 steps listed are:

1. Ensure clinical studies and publications address clinically important questions.

2. Make public all results, including negative or unfavourable ones, in a timely fashion, while avoiding redundancy.

3. Improve understanding and disclosure of authors' potential conflicts of interest.

4. Educate authors on how to develop quality manuscripts and meet journal expectations.

5. Improve disclosure of authorship contributions and writing assistance, and continue education on best publication practices to end ghost-writing and guest authorship.

6. Report adverse event data more transparently and in a more clinically meaningful manner.

7. Provide access to more complete protocol information.

8. Transparently report statistical methods used in analysis.

9. Ensure authors can access complete study data, know how to do so, and can attest to this.

10. Support the sharing of prior reviews from other journals.

The authors commented: “Although framed in the context of industry sponsorship, many of these recommendations would enhance the credibility of clinical research publications in general, regardless of the funding source.”

US-based contract research firm Cetero has filed for bankruptcy protection after being put on notice by the FDA for alleged “misconduct and violations”.

The North Carolina company, which carries out early-stage clinical research and bioanalytics for a number of US pharmaceutical companies, was accused last year of faking research documents and manipulating drug samples.

The FDA has warned Cetero’s clients that they may need to repeat or confirm any studies Cetero carried out in support of their applications for regulatory approval between 2005 and 2010.

In July 2011, the FDA said it had uncovered “significant instances of misconduct and violations” at Cetero’s Houston facility.

According to Cetero’s bankruptcy filing, the FDA’s warning caused the company’s financial position to become “severely constrained” due to creditors declaring an event of default.

As part of the bankruptcy process, Cetero has reached a deal with certain lenders for the sale of the company’s assets, and has also secured Debtor-in-Possession financing of $15m to finance this process.

Over the first two months of 2012, Cetero’s revenue totalled $11m while the company had liabilities of $248 million and assets up to $10 million.

Many clinicians and scientists engaged in UK clinical research are doctoring the data, according to a new BMA survey.

Of 2782 UK-based doctors and scientists who responded to a short questionnaire, 354 (13%) said they had direct experience of their colleagues “adjusting, excluding, altering or fabricating data”.

In addition, 163 respondents (6%) said they were aware of cases where research misconduct had not been properly investigated by the relevant clinical or academic body.

The survey follows a recent BMJ editorial claiming that under-reporting of clinical trial data by pharmaceutical companies is widespread and poses “a threat to the integrity of evidence-based medicine”.

Now, showing the other side of the coin, the BMJ has stated that research misconduct is “alive and well" in the UK.

The questionnaire was sent to 9036 UK-based clinicians and scientists, of which 2782 (31%) responded. The BMJ report noted that some response bias was likely: “Those with cases to report may have been more liable to respond.”

“While our survey can't provide a true estimate of how much research misconduct there is in the UK, it does show that there is a substantial number of cases and that UK institutions are failing to investigate adequately, if at all,” said Dr Fiona Godlee, BMJ Editor in Chief.

Dr Elizabeth Wager, Chair of the Committee on Publication Ethics (COPE), commented: “This survey chimes with our experience where we see many cases of institutions not co-operating with journals and failing to investigate research misconduct properly.”

The report calls into question the superiority of ‘pure’ clinical and scientific research over industry-sponsored research in terms of the reliability of its conclusions.

UK pharmaceutical companies conducting early stage clinical trials will be able to collaborate more extensively with leading medical academics following the government’s launch of two pioneering partnership programmes designed to accelerate the development of innovative treatments from lab to patient.

The first two National Institute for Health Research (NIHR) translational partnerships – in respiratory and joint-related inflammatory diseases – will give life science companies access to a ‘unique network of top clinical scientists’ in government-funded research facilities, leading universities and the NHS.

The government says the partnerships will also provide unparalleled access to ‘cohorts of well-characterised patients’ – cutting through red tape to speed up the recruitment and testing of NHS patients, and ensuring quicker access to life-changing new therapies.

Access to the Partnerships will be via the NIHR Office for Clinical Research Infrastructure (NOCRI), meaning that when a company wants to collaborate, only one legal agreement is required rather than having to negotiate with each NHS Trust and University.

The new initiative represents an attempt to address a sharp decline in the UK’s reputation as a world-class location for medical research, and also reflect a growing appetite across the pharmaceutical industry to find efficiencies in its R&D model through greater collaboration with external specialists.

David Willetts, Minister for Universities and Science, said the research partnerships would provide a unique model for collaboration between the life sciences industry, the NHS and universities. “They will be a key driver of growth and innovation, reducing the time it takes to translate research into benefits for patients and the economy,” he said.

The ABPI has welcomed the initiative, citing collaborative working with clinical academic investigators as pivotal to the changing model of drug development for the pharmaceutical industry. “Translational Research Partnerships offer an efficient and effective way for companies to work with some of the UK’s leading translational research experts through NOCRI,” said Dr Allison Jeynes-Ellis, Medical and Innovation Director, ABPI. “Companies will see great advantages to working with the partnerships and consequently they will attract ground-breaking research into the UK.”

The government will provide £1.3 million to help set up the first two partnerships; inflammatory respiratory disease and joint and related inflammatory diseases. The NIHR partnership for translational research on respiratory diseases – such as asthma, COPD, allergies, cystic fibrosis and acute lung injury – includes hospitals and universities in Northern Ireland, Oxford, Manchester, Southampton and London. The partnership in joint and related inflammatory diseases, such as rheumatoid arthritis, osteoarthritis, and synovitis, includes Barts and the London NHS Trust, the University of Birmingham, UCLH and Cambridge University.

Terms of the partnership are likely to include identifying more efficient ways of tapping into suitable patient groups for clinical trials, and unlocking funding beyond life science investment in exchange for shared intellectual property rights for any breakthrough discoveries.

The EMA has started a new review of the cardiovascular safety of non-selective NSAIDS (non-steroidal anti-inflammatory drugs).

The CHMP’s previous opinion of NSAIDs in 2006 was positive, but a small possibility of an increased risk of thrombotic events such as heart attack or stroke could not be excluded, particularly involving high doses and long-term treatment with NSAIDs.

The CHMP will update its opinion in light of recently published evidence from the independent research project Safety Of non-Steroidal anti-inflammatory drugs (SOS) funded by the European Commission.

NSAIDS have been subject to several European reviews in relation to gastrointestinal and cardiovascular safety and the occurrence of serious skin reactions since the CHMP’s 2006 opinion.

It will review the results thoroughly, together with other available clinical research data, to distinguish the need to update the CHMP’s 2006 opinion.

The FDA has approved Boehringer Ingelheim’s Combivent Respimat, a propellant-free inhaler for patients with chronic obstructive pulmonary disease (COPD).

The product has been developed to replace the Combivent MDI, which contains chlorofluorocarbons (CFCs), in response to the Montreal Protocol treaty to phase out the use of inhalers releasing CFCs or hydrofluoroalkane (HFA) propellants into the atmosphere.

The product uses a slow-moving mist to deliver ipratropium bromide and albuterol sulfate, requiring only one inhalation per dose compared to Combivent MDI, which requires two inhalations per dose.

Both inhalers are the only short-acting bronchodilator products that offer two different medicines in a single inhaler. Clinical research in COPD patients has shown that the combination of ipratropium bromide and albuterol sulfate provides patients significantly greater improvement in lung function than either component alone.

Janssen Pharmaceuticals’ protease inhibitor (PI) Incivo (telaprevir), to treat adults with genotype-1 chronic hepatitis C, has been launched in the UK.

The direct acting antiviral (DAA) PI uses telaprevir, a new class of medicine which directly targets the hepatitis C virus, offering patients further help with clearing the virus in combination with the current standard treatment of peginterferon alfa and ribavirin.

Professor Graham Foster at Queen Mary's University Hospital of London, said: “For many adults with chronic genotype-1 hep C, treatment with a telaprevir based regimen could provide a shorter treatment duration with improved response rates compared to standard treatment.”

The marketing authorisation of the therapy was based on clinical research gathered from three Phase III clinical trials involving more than 2,290 hep C patients. Results showed that Incivo cured the virus in almost twice as many previously untreated patients and in almost four times as many who had previously relapsed following treatment.

Incivio was co-developed by Vertex Pharmaceuticals and Tibotec, an affiliate of Janssen Pharmaceuticals and the company responsible for marketing telaprevir in Europe.

Approximately 216,000 to 466,000 people are infected with chronic hepatitis C in the UK, of which only 80,000 have been diagnosed. The standard treatment for hep C, peginterferon alfa and ribavirin, is successful in about 50% of patients with genotype 1, leaving the other 50% without a successful treatment outcome.

The European Commission approved use of Incivo for to treat genotype-1 chronic hepatitis C virus in combination with peginterferon alfa and ribavirin in September 2011.

The FDA has approved Eli Lilly’s Cialis (tadalafil) to treat men with signs and symptoms of Benign Prostatic Hyperplasia (BPH) and Erectile Dysfunction (ED).

The drug works by inhibiting the phosphodiesterase type 5 enzyme (PDE5), helping to produce vascular relaxation and increase blood flow to the penis. These enzymes are also found in the prostate and bladder, where problems can occur with BPH.

Claus Roehrborn, Chairman of the Department of Urology at The University of Texas Southwestern Medical Centre, said: “Since many men who have ED also experience the signs and symptoms of BPH, a single medication approved to treat both may be a significant therapeutic option for men and physicians.”

The approval totals three indications: both ED and signs and symptoms of BPH separately, as well as for men who have both conditions.

Dave Ricks, Lilly USA President, said: “These additional indications for Cialis reinforce our commitment to providing medical innovation in the area of men's health.”

“We're encouraged that Cialis provides a new treatment option for men affected by both ED and the signs and symptoms of BPH,” commented Mr Ricks.

The FDA clearance was based on clinical research gathered from three placebo-controlled efficacy and safety studies involved 1,989 men.

BPH is a condition where the prostate enlarges, which can cause urinary problems. Approximately 50% of men between 40-70 years old suffer from erectile dysfunction. Several studies have shown that many men with ED also experience the symptoms of BPH.

The FDA has approved LeGoo from Pluromed, a gel that allows surgeons to temporarily stop blood flow during surgery involving blood vessels.

The temperature-sensitive gel forms a plug when injected in the bloodstream, stopping blood flow during surgery for up to 15 minutes, allowing surgeons to join blood vessels without clamps or elastic loops.

In cases where the plug needs to dissolve sooner, the surgeon can dissolve the gel plug by applying a cold pack or cold saline to the blood vessel.

The gel has been shown by clinical trials to avoid blood vessel damage and prevent blood flooding in the surgical area.

“LeGoo is an innovative device that offers surgeons an additional aid during vascular surgery,” said Christy Foreman, Director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health. “The gel’s unique properties may facilitate surgeries that entail the joining or grafting blood vessels.”

The FDA based the approval on studies showing that LeGoo is both biocompatible and non-toxic. Clinical trials involving 110 patients undergoing bypass surgery without stopping the heart proved that LeGoo was as safe and effective as vessel loops, commonly used to stop blood flow during coronary bypass surgery.

Based in Massachussetts, USA, Pluromed specialises in injectable plugs to control bleeding during surgery, based on its proprietary polymer technology.

Sanofi’s prostate cancer drug Jevtana (cabazitaxel) has not been recommended by NICE in draft guidance in combination with prednisone or prednisolone as a second line treatment.

NICE’s Appraisal Committee raised concerns about the medication’s cost effectiveness, its associated adverse effects and evidence supplied by the manufacturer.

Sir Andrew Dillon, NICE Chief Executive, says that the Committee was “particularly concerned” about the uncertainty on patients’ renal and cardiac systems.

A number of factors are taken into consideration by NICE’s Appraisal Committees when assessing the cost effectiveness of a treatment. These include the medication’s clinical effectiveness, its side effects, the benefits it brings to patients and the financial cost.

This formula then enables them to determine the cost of using the drug to provide a year of the best quality of life available or quality adjusted life year (QALY). NICE says they usually recommend treatments that cost around £30,000 per QALY or less, however the cost of Jevtana was far greater than this figure.

“The manufacturer of cabazitaxel provided one study on the effectiveness of the drug; in this study cabazitaxel was shown to extend life by approximately 10 weeks,” said Sir Andrew. “Although cabazitaxel has been shown to be effective, it is also associated with a number of adverse events.”

He added that the Appraisal Committee was also concerned about the “validity” of the health related information supplied by Sanofi after it provided one study which demonstrated a median overall survival gain of 2.4 months and an mean overall survival gain of 4.2 in its model.

“The Committee also felt that the treatment did not meet the criteria to be considered under NICE’s special arrangements for end of life, as based on the current data the length of the life extension could not be considered robustly proven to be at least three months,” added the Chief Executive.

“Once all these factors had been taken into account it was estimated that the cost per QALY would be more than £89,000. Therefore the committee concluded that cabazitaxel would not be a cost effective use of limited NHS resources.”

If a drug does meet the criteria to be considered under the Institute’s supplementary advice for end of life treatments, a higher cost per QALY may be accepted by NICE. There is currently no set threshold cost per QALY that meets this criterion, but since the supplementary advice was introduced, the only drug recommended under this method has been Sunitinib for renal cell carcinoma at a cost of £50,000.

NICE said that Javtana did not meet this criterion because the Committee did not consider the length of the life extension to be “sufficiently robust”.