Making sense of side effects

Last Wednesday, the MRC Centre for Drug Safety Science at the University of Liverpool launched a public guide, Making Sense of Drug Safety Science, in collaboration with Sense About Science.

Side effects, or adverse drug reactions, are a big public health concern and can be a barrier to the development of new medicines, causing many promising new drugs to be dropped at the development stage or in clinical trials. As the guide explains, drug safety science is helping us learn more about side effects, what gives rise to them and the harm they can cause. Researchers are working on developing tests to predict who will experience side effects. This can allow a beneficial drug to continue and to be used by people who are not at risk.

I have often been asked to tackle this subject by outspoken defenders of alternative treatments. This post will hopefully explain how we can establish whether the benefits outweigh the harms, what some of the pitfalls are, and what we can do to improve. I would also urge those using unregulated treatments to consider what safeguards are in place to research the side effects of these, to inform the public about the harms they may cause and to protect us from them.

If a medicine contains an active ingredient and is able to provide benefit then it will inevitably also have side effects. This is true for conventional medicines, herbal remedies and unregulated, untested concoctions alike.

Many promising new treatments never reach the market. Attention grabbing news stories are often based on very early research results and ignore the hurdles that drugs must overcome to make it to market.

Sometimes what works in a lab dish or in an animal doesn’t work in a person. And trials on potentially effective drugs are sometimes stopped because of safety concerns. Drug safety research is working to reduce or even eliminate some of these side effects.

Before a drug is given to anyone, preclinical studies are carried out on animals in order to learn more about any possible toxic effects. Clinical trials then test the efficacy and safety of the most promising drug candidates. Regulators will then decide whether to license the drug and for this to happen, the benefits have to outweigh the harms.

I hope that those defenders of alternative medicine are still with me. Yes, I’m aware that I’m discussing an ideal world and that real life is far from that. There is no mechanism to ensure drug companies supply all relevant information to regulators and many clinical trials on medicines in current use were not registered or reported. If this worries you, I urge you to lend your support to the All Trials campaign.

Rare side effects may not emerge until after a drug has been marketed for several years. Some effects may only be found in a small subset of the population, such as people who have an unusual genetic condition or an underlying disease that disrupts the way the drug is eliminated from the body.

If severe side effects become apparent after a drug is on the market then regulators can step in and make new recommendations or even have the drug withdrawn. Here in the UK, the MHRA’s Yellow Card scheme provides a valuable resource to help identify emerging drug safety issues. It allows patients to report any side effects that they suspect may have been caused by medicines.

It is worth noting that no such safeguards exist for unregistered and therefore unregulated alternative treatments. For example, colloidal silver is not regulated as a medicine and has not been shown to be effective for any condition, but nevertheless carries a risk of severe and irreversible side effects.

For treating life threatening illnesses, more severe side effects are acceptable if the drug could cure or significantly prolong life. It may also be licensed if a very small number of people respond badly during a trial. Doctors will be made aware of the risk so that they can monitor patients or avoiding prescribing the drug to those most at risk.

Again, I’m discussing an ideal world. Because chemotherapy can kill cancer cells and lead to recovery, it is also acceptable for it to have severe side effects. This means that advanced cancer patients may wish to avoid some conventional treatments and are especially vulnerable to the false promises of snake oil peddlers, quacks and vultures. Alternative cancer treatments are typically unregistered, unregulated and unproven.

Because his patients have life threatening cancers, Stanislaw Burzynski was able to abuse the clinical trials process and continued to prescribe antineoplastons –  unproven drugs with a questionable safety record – for decades. Although the US medicines regulator, the FDA have now stopped the trials, Burzynski is still allowed to prescribe chemotherapy drugs “off label” in untested combinations.

This could be a problem because interactions can make a drug more or less powerful or can increase side effects. Users of alternative medicines and supplements should also be warned that because of interactions, some of these, such as St John’s Wort, could prevent certain drugs from working.

Side effects could also happen because of increased sensitivity in some individuals, increased exposure, immune responses, or genetic or environmental factors.

Research into the mechanisms by which drugs cause side effects can put us in a better position to make drugs safer. Drug safety scientists can investigate the mechanisms of drugs that have been withdrawn from use or that are associated with a particular side effect. For example, the anti-HIV drug abacavir was prescribed less and less because it was linked to severe skin reactions. A genetic test has now been developed to screen for patients who would be susceptible and abacavir continues to be used as an effective drug.

It is right to be concerned about adverse drug reactions, but wrong to assume that unproven alternatives are either effective or safe. It is not always possible to tell whether the benefit of a treatment will be worth the side effects but things are improving. I would urge anyone with concerns not to panic, but to read the guide and  learn about how new treatments reach the market, why side effects happen and what is being done to make things better.

Related articles

Making Sense of Drug Safety Science: Investigating the science of side effects Sense About Science

Publication of Making Sense of Drug Safety Science: Investigating the science of side effects Centre for Drug Safety Science, University of Liverpool, 13/11/13

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7 responses to “Making sense of side effects

  1. Pingback: Daily Overload – News in short (18-11-2013) « The Skeptical Bear

  2. Chemotherapy is a multi-billion dollar industry.

    Cancer research has been ongoing for at least 100 years. Multi-billions if not trillions of money has been spent on the research of cancer and its potential cure.

    Can cancer be cured? Cancer is determined as abnormal growth of naturally occurring cells. Cancer is a natural phenomena and I would dare say it occurs in every single human during their life.

    Something determines what causes a person to “succumb” to cancer and perhaps die. Has the millions of hours of research determined this yet? Is there a cure or is this the perpetual war within humans?

    Perhaps rather than spending billions/trillions on how to treat (cure is unlikely if it hasn’t been found yet) the “disease” in pounds/dollars/yen etc or hours, the research should focus on how to PREVENT cancer (uncontrolled cell growth) in the first place.

    This of course would severely dent the multi-billion dollar industry of treating cancer, but it would bring a great deal of happiness to lives across the globe.

    These are the big questions that should be asked in the world rather than just being made to feel guilty about not donating enough to cancer research charities.

    I am not looking for an argument here. An intelligent discussion though.

    • Both approaches are required. The reality is with the state of current knowledge and the equal reality that the treatment option is still the most accessible, pragmatic and realistic approach things won’t change quickly.

      We can’t stop DNA mutating. Epidemiological studies often produce the broadest of stroke information, smoking being a notable exception. Look around – people still smoke despite overwhelming evidence. Motivation once diagnosed with cancer is radically different to being told to change your lifestyle prior to developing it.

      Sunscreens will probably reduce the risk of skin cancers if used within the lifespan of the active ingredients and re-applied regularly and especially after swimming at the beach etc., and if it blocks all risk factor wavelengths. I think I am right in saying that the evidence suggest skin cancer has increased despite the availability of sunscreens.

      In an ideal world prevention rules, in a realistic world pragmatically treatment is a priority, and is increasingly successful.

      Your unspoken assumption is prevention isn’t a priority. Why might that be the case? Are you suggesting such work is actively suppressed? If so, based on what evidence ?

  3. Hi Brasso – well, OK, but money *is* spent on cancer prevention http://www.ncri.org.uk/initiatives/prevention. I’m pretty sure even cure-focused cancer research casts an eye over uncontrolled cell growth too…

    You might also like “Helping more people survive cancer” https://www.gov.uk/government/policies/helping-more-people-survive-cancer which covers prevention, diagnosis and treatments.

  4. Perhaps a little off topic but can you clarify your view of off label prescribing please? While I find the abuses of the system both here and in the USA reprehensible, and a disgusting abuse, off label prescribing is an essential option in an imperfect system. My particular angle on this is drugs used in some rare conditions in children where no good clinical evidence, in the form of RCTs, exists and would be unlikely to ever be funded or performed. I don’t feel qualified to comment on how regulation could be improved but it probably needs to be, without restricting those cases where it is clinically justified and provides improved quality of life with measurable low risk.

    I also encourage all readers to support the All Trials campaign. Success in this would ultimately save both money and lives.

    • Thanks for your comment. Because I was trying to write a fairly short summary, I didn’t want to say too much about off label prescribing. I wasn’t intending to suggest it should be stopped altogether, but pointing out that things can be more complicated than the ideal world scenario I had just set out. I think there needs to be some leeway, but if there is leeway then of course there is a risk it will be abused. I was also wanting to make an example of Burzynski – who treats patients with unapproved and untested combinations of drugs and who has abused the clinical trials process. In my view, this has put patients at risk and regulators have failed to protect the public.

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