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Updated: 6 hours 57 min ago

Pharmacological interventions for self‐harm in adults

Thu, 01/14/2021 - 10:24
Pharmacological interventions for self‐harm in adults Cochrane authors have reviewed the international literature regarding pharmacological (drug) and natural product (dietary supplementation) treatment trials in the field. A total of seven trials that met inclusion criteria were identified. There is little evidence of beneficial effects of either pharmacological or natural product treatments. However, few trials have been conducted and those that have are small, meaning that possible beneficial effects of some therapies cannot be ruled out.
  Why is this review important?
Self‐harm (SH), which includes intentional self‐poisoning/overdose and self‐injury, is a major problem in many countries and is strongly linked with suicide. It is therefore important that effective treatments for SH patients are developed. Whilst there has been an increase in the use of psychosocial interventions for SH in adults (which is the focus of a separate review), drug treatments are frequently used in clinical practice. It is therefore important to assess the evidence for their effectiveness.  

Who will be interested in this review?
Hospital administrators (e.g. service providers), health policy officers and third party payers (e.g. health insurers), clinicians working with patients who engage in SH, patients themselves, and their relatives.

What questions does this review aim to answer?
This review is an update of a previous Cochrane Review from 2015 which found little evidence of beneficial effects of drug treatments on repetition of SH. This update aims to further evaluate the evidence for effectiveness of drugs and natural products for patients who engage in SH with a broader range of outcomes.

Which studies were included in the review?
To be included in the review, studies had to be randomised controlled trials of drug treatments for adults who had recently engaged in SH.

What does the evidence from the review tell us?
There is currently no clear evidence for the effectiveness of antidepressants, antipsychotics, mood stabilisers, or natural products in preventing repetition of SH.

What should happen next?
We recommend further trials of drugs for SH patients, possibly in combination with psychological treatment. Thursday, January 14, 2021

Cochrane Methods Rapid Reviews vs COVID-19: How to review evidence fast and maintain quality

Wed, 01/13/2021 - 12:50

During the COVID-19 pandemic, people relied on research evidence to help make decisions that affected the health of millions. Cochrane had the skills and experience to draw together the research evidence. We needed to work more quickly than our usual systematic review process, which sometimes takes many months to search widely and assess research. Cochrane Methods Rapid Reviews group developed a way to create rapid reviews, which streamlined our processes to create high-quality reviews very quickly.


In March 2020, the Cochrane Methods Rapid Reviews group launched guidance about how to undertake a rapid review. This group will continue to develop guidance as we learn more about the most efficient and useful approaches. They also introduced new systems to produce rapid reviews about COVID-19 quickly and provided advice and training to teams conducting rapid reviews, living evidence mapping and living systematic reviews.

Read more about what this group accomplished and learnt in the process in this short case story.

Wednesday, January 13, 2021

Cochrane Oral Health vs COVID-19: Evidence to help reopen dental services

Tue, 01/12/2021 - 11:45

At the start of the COVID-19 pandemic, many countries implemented lockdowns or stay-at-home orders. Most dental services provided only emergency treatment so patients and dental professionals could stay safe. This left many people in pain or without access to care. As countries began to ease their lockdown restrictions, policy-makers and dental professionals wanted to know when and how best to reopen dental services. Cochrane Oral Health aimed to help them make decisions informed by evidence.

Cochrane Oral Health compiled research and international guidance about COVID-19 and dental services. They developed a webpage summarising relevant guidance documents for dental care. They targeted their materials to policy-makers who needed to make decisions about how dental practices could reopen.

Learn more about this collaborative effort to improve evidence-based decision making during COVID-19 in this short case story.

Tuesday, January 12, 2021

Let's talk e-cigarettes Podcast

Fri, 01/08/2021 - 22:06

'Let's talk e-cigarettes'' is a podcast talking about the latest research on e-cigarettes and how new research changes what we know about them. It's hosted by Cochrane Tobacco Addiction researchers Dr Jamie Hartmann-Boyce and Dr Nicola Lindson based at the University of Oxford, through funding from Cancer Research UK. You can listen to the podcast on iTunes, Spotify, or below. 

In this initial podcast, they discuss evidence from a Cochrane Living Review of e-cigarettes for smoking cessation, what they found in a recent search, and a deep-dive into one recent study with Professor Mark Eisenberg. Transcript of podcast

Tuesday, January 12, 2021

Cochrane France vs COVID-19: Mapping ‘real-time’ evidence about COVID-19

Fri, 01/08/2021 - 15:51

Decision-makers are making decisions about COVID-19 that affect the health of millions of people. Researchers have been quick to do studies about COVID-19, but it can be difficult to stay up to date. Cochrane France wanted to bring together the global evidence about preventing, treating and rehabilitating people with COVID-19 regularly and in one place, so they collaborated on the COVID-NMA initiative.

The COVID-NMA initiative has three overarching parts:

  1. Mapping randomized controlled trials about the effectiveness of interventions for preventing and treating COVID-19 and assessing vaccines.
  2. Living evidence syntheses of the effectiveness of treatments for COVID-19.
  3. Recording data about the quality and transparency of the study designs.

Read more details about these parts of the initiative, and what this collaboration has been able to achieve and impact through this work in this  short case story.

Friday, January 8, 2021

Chilean Satellite of Cochrane EPOC vs COVID-19: Supporting decision makers

Fri, 01/08/2021 - 12:56

The new Chilean Satellite of the Cochrane Effective Practice of Care  (EPOC) Review Group works with the Ministry of Health to help inform decisions.

In April 2020, the Chilean Satellite of Cochrane EPOC contacted the Department of Health Technology Assessment and Evidence Based Health in the Chilean Ministry of Health (HTA). They knew that the Ministry was likely to need evidence-based responses to the COVID-19 pandemic. The Review Group staff suggested that they could help to summarise the existing evidence so it could support the Ministry of Health at a time when rapid decision making was needed.

As of December 2020, the Chilean Satellite of Cochrane EPOC had produced 4 SUPPORT summaries supporting the Chilean Ministry of Health’s questions on COVID-19, with another 10 in progress.

They have presented the summaries directly to over 30 policy makers at the Ministry, including the regional Heads of Department. Feedback from the Ministry was that they were grateful for this work and that it was presented in a way that could be used in decision making.

To learn more about this work about how Cochrane has worked with policy makers, read this short case story.

 Read the case story in Spanish

Friday, January 8, 2021

Cochrane Rehabilitation vs COVID-19: Compiling the best available evidence rapidly

Fri, 01/08/2021 - 12:31

Many experts published their opinions about the impact of COVID-19 on rehabilitation early on, but none were based on real-world experience. Cochrane Rehabilitation wanted to share information rapidly as it emerged so rehabilitation services and patients around the world would know how the pandemic might affect them.

Since March 2020, Cochrane Rehabilitation have been compiling the best evidence available into a living rapid systematic review. They worked with the World Health Organization Rehabilitation Programme to identify the highest research priorities, and jointly defined the topics for which to search the best available evidence about the impact of COVID-19. These were also used to develop a Cochrane Library Special Collection.

They also developed an online interactive living evidence map which synthesises research relevant to the needs and priorities and provides an interactive access to the current results.

Learn more about the impact of this work by Cochrane Rehabilitation by reading short case story.

Thursday, January 14, 2021

Cochrane South Africa vs COVID-19: Very rapid reviews to inform National treatment Guidelines

Thu, 01/07/2021 - 19:56

There were no prevention or treatment protocols in place when COVID-19 reached South Africa. Policy-makers needed to work rapidly to support our diverse communities.  There were thousands of studies emerging from around the world, but there was a lot of duplication, variable quality and sometimes contradictory findings. The South African (SA) GRADE Network, co-lead by Cochrane South Africa and the Centre for Evidence-based Health Care, wanted to help policy-makers make decisions based on the best available research evidence in a timely way.

The SA GRADE Network worked with a sub-committee of the National Essential Medicines List Committee (NEMLC) from the South African National Department of Health. The sub-committee prioritised research questions. The SA GRADE Network worked with them to complete rapid reviews to answer these questions within 7-10 days.

Members of the SA GRADE Network worked on these rapid reviews with members of the Government sub-committee. This novel approach meant that they could work collaboratively and build relationships, ensuring that the reviews met policy-makers’ needs.

Read more about Cochrane South Africa’s work on this Network and what they achieved in this short case study. 

Thursday, January 7, 2021

Featured Review: Does behavioural support help people to stop smoking?

Thu, 12/31/2020 - 16:48
Behavioural interventions for smoking cessation: an overview and network meta‐analysis

Key messages 

Behavioural support can help more people to stop smoking for six months or longer, without causing unwanted effects.

Some types of support appear to work better than others. More studies are needed to identify the best ways to support people who are trying to stop smoking, and to identify the best people to support them.

Stopping smoking

The best thing people who smoke can do for their health is to stop smoking. People breathe more easily and cough less when they stop smoking. Stopping also lowers their risk of getting lung cancer and other diseases.

How to help people stop smoking

Most people who smoke want to stop, but many find it difficult. People who smoke may use nicotine replacement therapy, such as nicotine patches or gum, or other medicines to help them stop. Behavioural support provides an alternative – or additional – way to help people stop smoking. Sometimes behavioural support can be combined with nicotine replacement or other medicines to help people stop smoking.

Types of behavioural support can include: advice and counselling on ways to make it easier to stop smoking; information about why or how to stop; or a combination. Behavioural support can be given in group sessions or one-to-one.

Why did the authors do this Cochrane Review?

The authors wanted to find out:

  • which types of behavioural support work best to help people stop smoking;
  • the best ways to give behavioural support (including the best people to give it); and
  • what aspects of behavioural support help someone to stop smoking.

They also wanted to know if behavioural support can cause any unwanted effects.

What did authors do?

They searched for Cochrane Reviews of behavioural support to stop smoking, to identify relevant studies of adults who smoked. They then compared the studies with each other, to find out how well the different types of behavioural support helped people to stop smoking.

Search date: the authors included evidence published up to July 2020.

What they found

The authors found 33 Cochrane Reviews, from which they identified 312 relevant studies in 250,503 adults (aged 18 to 63 years) who smoked cigarettes. The studies investigated 437 different combinations of ways to stop smoking.

The studies looked at the following types of behavioural support, among others:

  • giving someone information about their test results, or their risk of smoking-related disease;
  • counselling (face-to-face, by telephone or by video call);
  • self-help materials, resources, and reminders by mobile phone messages or apps;
  • rewards (money, or a chance to win money by entering competitions);
  • exercise-based support; and
  • hypnotherapy.

In the studies, a variety of people provided behavioural support, including: doctors, consultants, nurses, pharmacists, dentists, counsellors and lay health advisors.

Most studies were conducted in the USA or Western Europe; 115 studies took place in healthcare settings and 195 took place in the community. On average, people taking part in the studies were followed up for 10.5 months.

The studies compared the effects of behavioural support with:

  • no behavioural support;
  • usual or standard care;
  • less-intense forms of the behavioural support; or other approaches.

The authors compared all treatments with each other using a mathematical method called network meta-analysis.

What are the main results of this review?

Compared with no behavioural support it was clear that some types of behavioural support increased people's chances of quitting for six months or longer, including: counselling and giving them money for successfully stopping smoking. More people stopped smoking with these types of support whether or not they were also taking medicines to help them stop smoking.

Behavioural support by text messages probably helped more people to stop smoking than no support.

Compared with no support, tailoring behavioural support to the person, or group of people, trying to stop smoking probably slightly increased how many of them stopped smoking, as did support that focused on how to stop smoking.

Increasing the intensity of the support given, such as contacting people more often or having longer sessions, modestly increased how many people stopped smoking.

The authors are uncertain about:

  •  the effects of other types of behavioural support, including hypnotherapy, exercise-based support, and entering competitions; and
  • the effect of who gives the behavioural support.

Only some studies reported results for unwanted effects; in these, behavioural support did not increase the numbers of any unwanted effects.

How confident are the authors in these results?

The authors are confident that counselling and rewards of money help people to stop smoking; they do not expect that more evidence will change these results. They are less confident in the results for other types of behavioural support, and about who gives the support and how. They found limitations with some of the studies, including how they were designed, conducted, and reported. These results are likely to change when more evidence becomes available. More studies are needed.

Tuesday, January 5, 2021

Cochrane Sweden collaborates on trial transparency report

Tue, 12/22/2020 - 15:17

Cochrane Sweden, in collaboration with TranspariMED, recently published a report on clinical trial transparency in Sweden.

The report draws on data from the EU Trials Tracker and summarises the current extent of clinical drug trial reporting for different organisations in Sweden. Under the European Commission’s Clinical Trial Regulation, clinical trial sponsors must post summary results to the EU Clinical Trials Register within one year of a study ending, or six months for paediatric trials.

The report found that over 70% of clinical trials whose results were verifiably due had not yet posted results. This is far below the European average. However, several Swedish trial sponsors have already pledged to make improvements.

Matteo Bruschettini, Director of Cochrane Sweden, says of the report: “Cochrane Sweden, which was awarded full independent Cochrane centre status in 2020, promotes initiatives to improve the reporting of all studies. Our hope is that this report and the linked implications and recommendations can help to facilitate improved reporting of clinical trials within Sweden. We share the goal to get more complete and accurate evidence on which to make informed health decisions within healthcare, and better health for everyone.”

Cochrane supports clinical trial transparency. We rely on the availability of results from clinical trials to produce high quality and relevant systematic reviews. When trial results – whether positive, negative, or neutral – are not published, it is not possible to make truly evidence-informed decisions about healthcare, and people can be put at risk of harm.

Tuesday, December 29, 2020

What are the most effective interventions during pregnancy for preventing stillbirth?

Mon, 12/21/2020 - 15:35

Antenatal interventions for preventing stillbirth, fetal loss and perinatal death: an overview of Cochrane systematic reviews

A stillbirth is generally defined as the death of a baby before birth, at or after 24 weeks of development. It is most common in low‐ and middle‐income countries but also affects people in high‐income countries. Numbers of stillbirths have not fallen much in the last 20 years and, despite the high numbers, it is not widely recognised as a global health problem.

This overview of Cochrane systematic reviews included 43 Cochrane reviews that assessed 61 different ways of preventing stillbirth during pregnancy, or infant deaths around the time of birth. However, few of these provided any clear evidence of an effect during pregnancy to reduce the risk of stillbirth or infant death. They were grouped into four different areas: nutrition, preventing infection, managing mothers' other healthcare problems, and looking after the baby before it is born.


  • Giving mothers balanced energy and protein supplements to increase the growth of the baby, particularly in undernourished pregnant women, probably reduces stillbirth by 40%.
  • For Vitamin A alone versus placebo (sham) or no treatment, and multiple micronutrients with iron and folic acid compared with iron with or without folic acid, there was clear evidence of no effect.

Prevention and management of infections

  • Insecticide‐treated anti‐malarial nets versus no nets may reduce loss of the baby in the womb (fetus) by 33%.

Prevention, detection and management of other healthcare problems

  • Where midwives were the primary healthcare provider, particularly for low‐risk pregnant women, loss of the fetus or infant deaths fell by 16%.
  • Having a trained traditional birth attendant versus having an untrained traditional birth attendant probably reduces stillbirth in rural populations of low‐ and middle‐income countries by 31% and infant death by 30%.
  • A reduced number of antenatal care visits probably results in an increase in infant death around the time of birth.
  • Community‐based intervention packages (including community‐support groups/women's groups, community mobilisation and home visits, or training traditional birth attendants who made home visits) may reduce stillbirth by 19%.

Checking the baby before birth

  • Cardiotocography measures the baby's heart rate and contractions in the womb. It can be recorded automatically by computer or manually, with pen and paper. Computerised cardiotocography to monitor baby’s well‐being in the womb, by measuring contractions, probably reduces the rate of infant deaths around the time of birth by 80% when compared with traditional cardiotocography.

The overview was uncertain about the effects of other methods.

Further high‐quality RCTs are needed to evaluate the effects of antenatal preventive interventions and which approaches are most effective to reduce the risk of stillbirth. Stillbirth (or fetal death), perinatal and neonatal death need to be reported separately in future RCTs of antenatal interventions to allow assessment of different interventions on these rare but important outcomes and they need to clearly define the target populations of women where the intervention is most likely to be of benefit.

Dr. Erika Ota, lead author and professor at the St. Luke’s International University in Japan says, “Stillbirth can be very upsetting for families and looking at what the evidence was across Cochrane systematic reviews was important to us. Cochrane systematic reviews provide high quality evidence. We assessed 43 Cochrane reviews with over 60 different ways to prevent stillbirth and infant deaths at birth.

We found that from these 60 different interventions, most interventions were unable to demonstrate a clear effect in reducing stillbirth or perinatal death. However, several interventions suggested a clear benefit to preventing still birth and infant deaths at birth, such as balanced energy/protein supplements, midwife‐led models of care, training versus not training traditional birth attendants, and antenatal cardiotocography. Possible benefits were also observed for insecticide‐treated anti‐malarial nets and community‐based intervention packages, whereas a reduced number of antenatal care visits were shown to be harmful.

The effectiveness of the methods used to prevent stillbirth varied depending on where they took place, highlighting that it is important to understand how they were tested. Unfortunately the findings cannot be applied to women in general and across all global settings but hope this overview will help show that further high-quality trials are needed in low- and middle income countries where a high burden of stillbirths occur.”

Wednesday, December 23, 2020

Cochrane Mexico vs COVID-19: Evidence to guide paediatric COVID-19 patient care

Mon, 12/21/2020 - 14:50

The first COVID-19 case in Mexico was announced on 28 February 2020, with an anticipation that the number of cases would rapidly increase, some cases even occurring in children. To address this need, Cochrane Mexico worked with paediatric infectious disease specialists to create a Guide for COVID-19 diagnosis and treatment in paediatric patients. The Guide is for physicians in emergency departments, family physicians, paediatricians, and physicians working on newly created COVID-19 dedicated teams.

To create this guide, Cochrane Mexico reviewed all available literature on the characteristics of the virus, the mechanisms of transmission, clinical presentation and initial treatment recommendations. They finished reviewing the literature and developing the Guide as quickly as possible, so that it was available by the time the first cases in children began to appear.

Learn more about this guide and how Cochrane Mexico adapted to the changing situation and availability of evidence in this short case study. 

Monday, December 21, 2020

Special healthy ageing issue of Cochrane Library app released, as WHO launches Decade for Healthy Ageing Baseline Report

Thu, 12/17/2020 - 14:40

2021-2030 was recently formally declared as the UN Decade of Healthy Ageing at the UN General Assembly. The Decade of Healthy Ageing aims to bring together governments, civil society, international agencies, professionals, academia, the media, and the private sector to jointly take action in order to improve the lives of older people, their families, and the communities in which they live.

The Cochrane-Campbell Global Ageing Partnership has been working with the World Health Organization (WHO) since 2015, and has actively supported preparations for the Decade. This includes co-authoring the WHO Decade of Healthy Ageing Baseline Report, which sets the stage for the Decade. The report was published today, 17 December, and references 13 Cochrane Reviews. Prof Tracey Howe, Director of the Cochrane Campbell Global Ageing Partnership, attended and spoke at the launch, alongside WHO leadership, policymakers and civil society representatives from around the world.

Special issue of the Cochrane Library App

To tie in with the launch of the WHO Decade of Healthy Ageing Baseline Report, we have also launched a healthy ageing-focused issue of the Cochrane Library App.

The Cochrane Library app presents the latest up-to-date evidence from the Cochrane Library in a convenient, easy to navigate format which provides you with relevant, accessible research, when you need it, from the world’s leading experts in evidence-informed health care.

All content is free and new issues will download regularly.



Thursday, December 17, 2020

Author Interview: Conflicts of interest in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews: associations with recommendations

Wed, 12/16/2020 - 20:42

In this short interview, PhD student Camilla Hansen Nejstgaard,  from Cochrane Denmark and Centre for Evidence-Based Medicine Odense (CEBMO) at the University of Southern Denmark, tells us about how conflicts of interest may impact on recommendations of drugs and medical devices. She is the lead author of a recently published Cochrane Methodology Review on this topic. 

What does this Cochrane review tell us about the impact of conflicts of interests in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews?

The findings from our review indicate that financial conflicts of interest are associated with favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. As an example, this means that guidelines written by authors with financial conflicts of interest, more often have recommendations that are favourable towards a new drug treatment than guidelines written by authors without conflicts of interest. We included 21 studies in our review and conducted four separate analyses on each of the four types of documents. These analyses provided similar findings but had some statistical uncertainty around the size of the effect .

We also investigated the impact of non-financial conflicts of interest. Such interest can occur, for example, when radiologists are authors of clinical guidelines on mammography screening (this is what we call specialty interests). However, we only found a single study investigating the impact from specialty interest in clinical guidelines and the results were uncertain, but indicated a similar direction of effect. 

Our findings are in line with previous Cochrane Reviews on conflicts of interest in primary research and systematic reviews. However, the results of our current review have less statistical precision and more research is needed, particularly on the impact of non-financial conflicts of interest.

What can guideline issuing organisations learn from this evidence?

Our findings suggest that authors of clinical guidelines may interpret evidence differently depending on whether or not they have financial conflicts of interest. Some guideline issuing organisations such as the National Institute for Health and Care Excellence, the US Preventive Services Task Force, and the World Health Organization have already implemented policies aimed at minimizing the potential impact from conflicts of interest. For example, by minimizing the number and role of guideline authors with financial conflicts of interest. Even though our review did not investigate the impact from such conflicts of interest policies, our findings support the practice of minimising conflicts of interest.

What should patients, doctors and healthcare decision makers take from this evidence?

Based on our findings, we suggest that patients, doctors, and healthcare decision makers primarily use clinical guidelines, opinion pieces, and narrative reviews that have been written by authors without financial conflicts of interest. If that is not possible, users should read and interpret the publications with caution. Furthermore, our findings suggest that if committee members, for example at a regulatory drug agency, are asked to vote on the recommendation of a drug approval, they may be more likely to vote in favour of approving the drug when they have financial conflicts of interest.

Why is this review important?

Recommendations in clinical guidelines, opinion pieces, and narrative reviews as well as decisions about which interventions are approved by advisory committees have substantial impact on the interventions offered to patients. It is therefore essential that such recommendations are evidence-based and as little influenced by conflicts of interest as possible. If not, we may end up wasting resources on treatments that do not actually work, or even harming patients.

Tuesday, January 5, 2021

Cochrane ENT seeks part-time Systematic Reviewer - Oxford, UK

Wed, 12/16/2020 - 18:18

Closing date: 7 January 2021 
Location: Oxford, UK

Cochrane ENT is looking for an experienced Systematic Reviewer to work with the Cochrane ENT team, based at Cochrane UK in Oxford. The main purpose of the role is to assist in the prioritisation of ENT topics and facilitate the completion of high-priority systematic reviews. The post-holder will also support the Cochrane ENT editorial team and authors with methodological advice.

Main duties of the post will include: leading scoping reviews to prioritise reviews in key ENT topic areas and devising template protocols, including core outcome measures; co-authoring Cochrane ENT protocols and reviews, usually as lead author; commenting editorially as a methods adviser on draft protocols and reviews.

You will have a MSc in a relevant area or a higher degree, plus a first degree in a health-related discipline or equivalent experience. You will have experience in conducting high-quality systematic reviews, including familiarity with Cochrane guidance and standards for the design, conduct and reporting of systematic reviews (e.g. MECIR and GRADE). Completion of at least one Cochrane review or systematic review for a guideline producer is desirable.

This part-time post is available immediately and is fixed-term for 12 months in the first instance. The part-time hours are 40% FTE (2 days per week) and we are also willing to discuss remote working options.


Wednesday, December 16, 2020 Category: Jobs

Cochrane Germany vs. COVID-19: Working together to share research evidence

Wed, 12/16/2020 - 16:08

During the COVID-19 pandemic, Cochrane Germany wanted to build partnerships to share the best available evidence with as many people as possible, and make the findings from Cochrane systematic reviews accessible to German-speaking audiences.

Cochrane achieved their goals in several ways.  They highlighted evidence and resources on their website and developed COVID-19 related blogs in partnership with Cochrane Switzerland and Cochrane Austria. They disseminated COVID-19 press releases to journalists, and partnered with the associated Institute of Evidence in Medicine (IfEM) at the Medical Center - University of Freiburg to create and coordinate a pool of pre-assessed studies and to produce continuously updated ‘living’ evidence syntheses and guidelines.

Read more about the success of Cochrane Germany during the COVID-109 pandemic in this short case story.

Friday, December 18, 2020

Featured Review: Drugs for correcting the basic defect in the most common cystic fibrosis-causing gene variant

Wed, 12/16/2020 - 11:24

Read this recently published Cochrane review about CFTR correctors, a therapy for cystic fibrosis targeted at specific variants (most commonly F508del)

In this review, the authors looked at drugs (or drug combinations) for correcting the basic defect in the most common cystic fibrosis (CF)-causing gene variant (F508del) and assessed their impact on outcomes important to people with Cystic Fibrosis, e.g. survival, quality of life (QoL), lung function and safety.

Professor Kevin Southern, lead author of this review, has been involved in the care of children with CF for over 30 years, and has a deep appreciation of the impact of this condition on the young people and their families. "It has been great to work with the team to produce this comprehensive review, which clearly identifies the positive impact that triple therapy has on the well being of people with CF. The benefits identified in trials will prove to be transformational for young adults with CF like Freya Miao (pictured here with her glass of milk to take this therapy), who can now focus on maintaining good health as they move through adult life."

He continued, "The review concludes that people with CF with one or two F508del gene variants will benefit from this intervention.  In some countries, people with this gene variant are not able to access this important new therapy because of both funding and regulatory issues, and this represents a significant inequality that needs to be addressed.”


The CF gene makes a protein that helps salts move across cells in many parts of the body; over 80% of people with Cystic Fibrosis have at least one copy of F508del, meaning they make a full length of this protein, but it can not move through the cell correctly. Laboratory experiments suggest that if this protein reaches the cell wall, it may be able to function, restore salt movement, and correct the chronic problems that people with Cystic Fibrosis experience. The authors examined several agents for correcting F508del. Their original review showed that while single drugs alone were not effective, they were when combined with other drugs. This updated review includes single, dual (corrector plus potentiator), and triple therapies (two different correctors plus one potentiator).

Study characteristics

The authors included 19 studies (2959 children and adults) lasting between 1 day and 24 weeks (with an extension of two studies up to 96 weeks). Eight studies (344 participants) compared monotherapy: 4PBA, CPX, lumacaftor, cavosonstat and FDL169) to placebo (dummy treatment containing no active medicine), six studies (1840 participants) compared dual therapy (lumacaftor-ivacaftor or tezacaftor-ivacaftor) to placebo. Five studies (775 participants) assessed triple therapy (elexacaftor-tezacaftor-ivacaftor or VX-659-tezacaftor-ivacaftor); only the combination with elexacaftor progressed beyond early studies. In 14 studies, participants had two copies of F508del, in two studies participants had one F508del variant and one different variant, while in three studies participants had either two copies of F508del or one copy of F508del and one different variant.

Key results

Monotherapy versus control

These studies did not report any deaths or clinically relevant improvements in QoL scores. There was insufficient evidence to show an effect on lung function. All studies reported side effects, but it is difficult to assess their relevance due to the range of effects and the small number of participants in the studies.

Dual therapy versus control

Neither the lumacaftor-ivacaftor or tezacaftor-ivacaftor studies in people with two copies of F508del reported any deaths and there were improvements in QoL and lung function. Pulmonary exacerbation (a flare-up of symptoms) rates were also lower. Neither combination therapy was linked to severe side effects, although people starting treatment with lumacaftor-ivacaftor experienced shortness of breath for one to two weeks, this usually stopped without further treatment. More concerningly, in longer studies some people taking lumacaftor-ivacaftor experienced a rise in blood pressure; two people (out of over 500) even stopped lumacaftor-ivacaftor treatment because of high blood pressure. These side effects were not reported for tezacaftor-ivacaftor. Tezacaftor-ivacaftor therapy has not yet been assessed in children with CF under 12 years old.

Triple therapy versus control

No deaths were reported in the three studies. Triple therapies improved QoL scores and lung function, with no difference in the number or severity of side effects; there was a longer time until the next pulmonary exacerbation. There is high-quality evidence that elexacaftor-tezacaftor-ivacaftor therapy is clinically effective with few side effects for pwCF with one or two F508del variants aged 12 years or older. Further RCTs are required in children (under 12 years) and those with more severe respiratory function. The side effect profile of elexacaftor-tezacaftor-ivacaftor therapy seems to be similar to tezacaftor-ivacaftor, but we need to collect information over the longer term.

Quality of the evidence

The overall quality of the evidence varied from low to high. There were generally few details about study design, so we could not make clear judgements on potential biases. We had fewer concerns with the larger more recent studies. In 10 studies, some results were not analysed or reported. Some findings were based on studies that were too small to show important effects and for nine studies the results may not be applicable to all pwCF due to the age (i.e. only adults or only children studied) or an unusual design (pwCF received monotherapy and then combination therapy).

Thursday, December 17, 2020

Behind the Numbers Podcasts speaks to Dr. Stevens from Cochrane Canada

Mon, 12/14/2020 - 17:46

Behind The Numbers is a podcast aimed at disseminating research, news, & educational resources pertaining to Epidemiology and Biostatistics. Led by Gabriele Zitikyte, MSc Epidemiology student and executive member of the Canadian Society of Epidemiology and Biostatistics (CSEB)-uOttawa chapter, the podcasts  feature interviews and discussions that highlight different areas within epidemiology.

Recently, they spoke to Dr. Adrienne Stevens, the Managing Director of Cochrane Canada. Dr. Stevens expands on the differences between rapid reviews and systematic reviews, as well as the many ways that Cochrane is doing its part in combatting COVID-19 by continuing to promote evidence-informed health decision making. Dr. Stevens covers the Cochrane work on rapid review methodology to other Cochrane COVID-10 projects, such as the COVID-19 Recommendations Map.

Monday, December 14, 2020

Join us - Join in - Make a difference

Mon, 12/14/2020 - 13:40

The Membership team in Cochrane's People Services Department are delighted to announce a new version of our Join Cochrane pages that lay out all the varied ways people can get involved with Cochrane’s work. At the heart of the new content are:

The pages also showcase the fantastic Membership badges, which are available for to download from the Cochrane Account portal.

This week, the total number of Cochrane Members and Supporters hit the 100,000 mark. This impressive figure reflects the fact that we encourage anyone interested in our work to create a Cochrane Account, which unlocks access to free resources such as Cochrane Evidence Essentials and opportunities to contribute as part of Cochrane Crowd, the Cochrane Consumer Network, or on our volunteer hub, Cochrane TaskExchange.

Many of those who join as Supporters, will progress to earn Membership. Testimonies from Cochrane Members who share their experiences of getting involved, show the real value of Cochrane Membership as a reward for contributing to our work.

Thanks to our amazing translation teams, most of whom are volunteers, these pages are available in different languages - and the translators will have earned Membership points for their hard work!

We would like to thank the Web Team, and the Knowledge Translation Department, for their help in preparing these pages and their translated versions.

Monday, December 14, 2020

Anti-IL5 therapies for chronic obstructive pulmonary disease

Mon, 12/14/2020 - 12:35
In this short interview, author Iain Crossingham, Consultant Intensivist and Respiratory Physician, tells us more about this review and the treatment of airways diseases.

Tell us about this Cochrane Review
This is an interesting time for the treatment of airways diseases. Traditionally we've thought of these as coming under two main headings, asthma and chronic obstructive pulmonary disease (COPD), plus a handful of other rarer conditions such as bronchiectasis. Characteristically asthma caused variation in lung function tests such as peak flow or FEV1, either over time or with medication whereas COPD is defined by lung function that didn't improve ("fixed airflow obstruction"). Basing diagnosis on one dimension of the disease process (how quickly someone come blow air out of their lungs) obviously misses many other aspects of these conditions including the symptoms that impact people on a day to day basis.
In the clinic, we come across many different disease traits, for example

  • Wheeze/airflow obstruction
  • Cough, either daytime or disturbing sleep overnight
  • Sputum production, either intermittent or continuous
  • Frequent "exacerbations" or flare ups of symptoms
  • Structural changes in the lungs seen on CT scans
  • Persistent breathlessness and exercise intolerance
  • Association of symptoms with exposures at work or elsewhere

Why was it important to do this systematic review?
People may experience any of these and other traits regardless of whether their "official" label is asthma or COPD (or something else). Identifying the traits present in a particular individual at a particular time is what the pragmatic physician does to help agree a personalised treatment plan with an individual patient. This presents a problem for someone trying to be "evidence based" as trials have mostly lumped participants into broad but heterogenous groups based on diagnostic labels.

Why is this review important for people living with COPD and the clinicians treating them?
We've tried in this review to look at what are considered "asthma" treatments (anti IL5 drugs) in individuals with COPD who nonetheless may have traits that might respond to these drugs. We'd planned specific subgroup analyses looking at those with raised levels of particular biomarkers such as peripheral blood eosinophil counts that might define certain traits. The included trials were somewhat of a disappointment, mostly taking all comers rather than targeting groups who theoretically might respond. These were "lumper" trials, looking for(and on the whole failing to find) a modest benefit in a whole population. As you might have gathered, I think we need to split these groups down and personalise our treatments.  
What can people living with COPD and clinicians treating them take from this evidence?
Should people living with COPD or their clinicians be racing to start anti-IL5 drugs? No. However this is hopefully just a start. In the future, I'd like to see a person with an airways disease (be it labelled asthma or COPD) be able to choose the evidence based treatments that work for their particular set of problems and avoid the therapies that aren't relevant to their manifesting disease traits. There is clearly a challenge to us systematic reviewers. How do we collect evidence when the diagnostic labels used in trials don't capture the breadth of the experience of those living with the conditions?

Monday, December 14, 2020