Friday, September 10, 2021

COMPARE AND CONTRAST

Experts make weak recommendation for medical cannabis for chronic pain


New guidance aims to address confusion around the role of medical cannabis in the management of chronic pain

Peer-Reviewed Publication

BMJ

In The BMJ today, a panel of international experts make a weak recommendation for a trial of non-inhaled medical cannabis or cannabinoids (chemicals found in cannabis) for people living with chronic pain, if standard care is not sufficient.

The recommendation applies to adults and children living with all types of moderate to severe chronic pain. It does not apply to smoked or vaporised forms of cannabis, recreational cannabis, or patients receiving end-of-life care.

Their advice is part of The BMJ’s Rapid Recommendations initiative - to produce rapid and trustworthy guidelines for clinical practice based on new evidence to help doctors make better decisions with their patients.

Medical cannabis is increasingly used to manage chronic pain, particularly in jurisdictions that have enacted policies to reduce use of opioids. However, existing guideline recommendations are inconsistent, and cannabis remains illegal for therapeutic use in many countries.

Today’s recommendation is based on systematic reviews of 32 randomised trials exploring the benefits and harms of medical cannabis or cannabinoids for chronic pain, 39 observational studies exploring long-term harms, 17 studies of cannabis substitution for opioids, and 15 studies of patient values and preferences.

After thoroughly reviewing this evidence, the panel was confident that non-inhaled medical cannabis or cannabinoids result in small to very small improvements in self reported pain intensity, physical functioning, and sleep quality, and no improvement in emotional, role, or social functioning.

The panel found no evidence linking psychosis to the use of medical cannabis or cannabinoids, but say they do carry a small to modest risk of mostly self limited and transient harms, such as loss of concentration, vomiting, drowsiness, and dizziness.

The panel was less confident about whether use of medical cannabis or cannabinoids resulted in reduced use of opioids, and found that potential serious harms including cannabis dependence, falls, suicidal ideation or suicide were uncommon, but this evidence was only very low certainty.

The recommendation is weak because of the close balance between benefits and harms of medical cannabis for chronic pain. However, the panel issued strong support for shared decision making to ensure patients make choices that reflect their values and personal context.

And they suggest further research should explore uncertainties such as optimal dose and formulation of therapy, and benefits and harms of inhaled medical cannabis, which may alter this recommendation.

In a linked editorial, researchers welcome this new patient centred guidance, but say clinicians should emphasise the harms associated with vaping or smoking cannabis, discourage self medication, and pay particular attention to vulnerable populations.

“Increased pharmacovigilance of all cannabis use remains a priority, along with an ambitious programme of rigorous research on the short and long term effectiveness and safety of individual cannabis products for specific types of chronic pain,” they conclude.

SUBJECT OF RESEARCH

ARTICLE TITLE

ARTICLE PUBLICATION DATE

Can medical marijuana effectively treat childhood epilepsy?

JOURNAL

DOI

Third of cancer drugs without proven clinical benefit continue to be recommended for patients


Reforms needed to promote clarity about the basis on which the FDA approves or withdraws cancer drugs and to change positive recommendations when post-approval studies are negative


Peer-Reviewed Publication

BMJ

One third of cancer drugs that received accelerated approval from the US Food and Drug Administration (FDA) continue to be recommended in clinical guidelines after their confirmatory clinical trials fail to show improvement on their primary endpoints, finds a study published by The BMJ today.

A primary endpoint is the main result that is measured at the end of a study to see if a given treatment has worked (eg. the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins.

The researchers say clinical guidelines “should better align with the results of post-approval trials of cancer drugs that received accelerated approval.”

The FDA’s accelerated approval pathway allows drugs onto the market before their effectiveness has been proven to hasten patients’ access to promising new drugs. But as part of this approval, the manufacturer must conduct post-approval trials to confirm clinical benefit (improved survival or quality of life in the case of cancer drugs). If these trials show no benefit, the drug’s approval can be withdrawn. 

However, post-approval trials can be delayed for several years, and the FDA has until very recently been slow in taking steps to withdraw the drug or indication when these trials are conducted and fail to demonstrate clinical benefit.

So a team of researchers in Canada and the US set out to investigate how the FDA handles cancer drugs that received accelerated approval but had negative post-approval trials, and whether these negative trials change treatment guidelines.

They searched the FDA database for all cancer drugs granted accelerated approval from the start of the programme in 1992 until December 2020 and identified 18 indications for 10 cancer drugs that failed to show clinical benefit in post-approval trials. 

Of these, the approvals for 11 (61%) were voluntarily withdrawn, one was revoked, and six (33%) remained on the drug’s label, over an average of four years.

The researchers then reviewed the latest FDA and National Comprehensive Cancer Network (NCCN) guidelines and found that most of these drugs continued to receive high level endorsement, sometimes even after approval for the given indication had been withdrawn or revoked.

These are observational findings and the researchers point to some limitations, such as relying on publicly available information and pending decisions from the FDA on certain approvals, which may have affected the accuracy of their results. 

Nevertheless, they say this is the most comprehensive study of its kind so far and the findings “reflect the lack of fulfilment of the compromise between speed and evidence that underpins the accelerated approval pathway.”

They acknowledge that a recent flurry of regulatory action “suggests that the FDA has paid greater attention to these situations in the past two years,” but call for additional guidance and reforms of the accelerated approval pathway “to assure that all FDA approved drugs are shown to be safe and effective for patients.”

[Ends]

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