Thalidomide: Nine things you didn’t know about the ‘poisonous pill’

Thalidomide was marketed to pregnant women as an antidote for morning sickness in the late 1950s, but the results were calamitous. An epidemic of babies born with various disabilities including limb, organ and neural damage led to its withdrawal from sale in November 1961. There were over 5000 known thalidomide survivors living worldwide in 2003, including 500 in the UK.

As a healthcare researcher, I had come to understand the thalidomide catastrophe as a systems failure: the disastrous outcome of an inadequate medications approval process. My dad, Dr Martin Johnson, was Director of the UK Thalidomide Trust between 2000 and 2014, and through him I had come to learn about its terrible impacts upon individuals and their families. I also understood that many survivors were still awaiting justice. However, in 2018, together with his co-authors Professor Ray Stokes and Tobias Arndt, dad published ‘The Thalidomide Catastrophe’, the first and only comprehensive history of thalidomide. Reading it led me to realise I had been seeing through a glass darkly. When laid bare, the thalidomide story is stunning, shocking and almost unbelievable. Here I share with you nine things I learned from the book:

Ed, aged 3

Ed, aged 3

  1. The full number of people affected by the drug reached tens of thousands. It is well known that thalidomide caused babies to be born with disabilities. However, it is highly likely that many other children died in the days and months after birth and that even more were miscarried or stillborn because of thalidomide. Johnson, Stokes and Arndt estimate that altogether, between 87,600 and 275,500 babies were affected.
  2. A single tablet had disastrous effects. Researchers have been able to link the days on which tablets were taken with specific forms of damage. For example, a tablet on days 21-22 after conception could cause damage to, or loss of the eyes. A tablet on day 24 could cause loss of the arms and a tablet on day 29 could cause loss of the legs. The key message from this is that the babies who survived thalidomide were those whose mothers took a tiny amount of the ‘poisonous pill’.
  3. Key players in the development of thalidomide are linked with the Nazi regime. The book explores this issue in meticulous depth and it is hard to summarise the evidence briefly. However, two things are clear. The first is that the Chief Scientist of Chemie Grunenthal, the Germany company who patented the drug, was Dr Heinrich Muckter. Muckter spent World War 2 (WW2) at an institution which tested drugs on Buchenwald concentration camp prisoners. The second is that Otto Ambros was a consultant for the Distillers Company, the British organisation which distributed Thalidomide in the UK. Ambros was sentenced to 8 years for his war crimes during WW2, which included using slave labour from the Auschwitz III-Monowitz concentration camp.
  4. Thalidomide seriously harmed adults too. When taken for more than 2 weeks, thalidomide could cause adults to contract ‘polyneuritis’, nerve damage involving symptoms such as tingling, numbness, excruciating muscle cramping and even partial paralysis. It could affect coordination, balance and the ability to walk. Altogether, around half a million adults were probably affected. “The Thalidomide Catatrophe” provides the response from Chemie Grunenthal to one affected surgeon who used the drug. “Thank you for your letter of 8th March 1960 in which you tell us you are increasingly suffering from paraesthesia and… probable polyneuritis… We wish to advise you that we have received no such reports to date” (p110). This letter was a lie: the company had received several reports and their false reassurance may have caused the surgeon to keep taking the harmful drug. As Johnson, Arndt and Stokes comment, these effects probably cost this surgeon his career.
    TIna Gallagher

    Tina Gallagher in 2002

  5. Warnings the drug was dangerous were ignored. To this date, Chemie Grunenthal claim that they could not have known about the harmful potential of Thalidomide. The evidence presented by Johnson, Stokes and Arndt makes this almost impossible to believe. For example, there is clear evidence Grunenthal’s Chief Scientist, Heinrich Muckter, received warnings a year before thalidomide even went to market from Dr Piacenza, an Italian doctor who undertook trials of the drug. Writing in 1956, Piacenza reported that the drug was unsuitable due to its toxicity. He described side effects in adult patients which included a whole-body rash and peripheral nerve damage. Reports from concerned physicians continued to be sent to Grunenthal, but the drug was not removed from market. Concerns were also raised about the potential harmful effects of thalidomide on unborn babies. For example, in 1959, scientist Dr Randolph Riemschneider raised concerns that thalidomide was causing birth defects in tadpoles he was experimenting with. As he later recorded, “we sent this information with photos to Chemie Grunenthal… Unfortunately, no answer was forthcoming” (p115).
  6. Even when its impact was known, Chemie Grunenthal continued to sell thalidomide. There were warnings that thalidomide was harmful before it even went to market. However, Chemie Grunenthal did not publicly acknowledge its harmful potential until 1961. In a speech on 14th July that year, Heinrich Muckter, Grunenthal’s Chief Scientist told his staff, “if I were a doctor, I would not prescribe Contergan [trade name for thalidomide] any more. Gentleman, I warn you… I see great dangers” (p41). Yet he didn’t withdraw the drug from sale until November that year. If he had pulled it immediately after his speech, more than 25% of the babies who were affected would have been saved.
  7. The impacts of thalidomide are sometimes invisible. Not all survivors were affected by the limb damage which is characteristic of thalidomide. As a toxic nerve agent, it also caused devastating hidden damage. Johnson, Stokes and Arndt report the situation of Julie Lane, whose mother had been supplied with the drug. Outwardly, Julie only had minor hand damage. However, at a young age, she developed epileptic fits. In her teens, she lost the use of her legs and later on, her arms. She also gradually lost her hearing and her sight. As her epileptic brain activity was not typical, her symptoms were misdiagnosed as being psychosomatic, and not of physical origin. This caused her problems to be stigmatised. However, a post-mortem conducted after she died aged 44 showed evidence of major internal damage which had been there since birth.
  8. Survivors still wait for justice. Chemie Grunenthal, the company which patented thalidomide, has never been held to account. A trial was called in 1968 but later suspended, apparently on the basis that “public interest in a continuation of the criminal prosecution no longer exists” (p.131). In the UK, Distillers, the company which distributed the drug paid out some compensation following a lengthy legal battle. However, survivors in some other countries have never received compensation, and all survivors are still waiting for an apology from Chemie Grunenthal.
  9. Some countries protected their populations from thalidomide. Several countries which considered licensing thalidomide denied or significantly restricted the sale of the drug. These included Turkey, East Germany, the USA and France. In Turkey, Dr Aygun undertook tests involving tissue cultures and concluded the drug was unsafe in 1960. In East Germany, the relevant officials had concerns based simply on the information supplied in the patent. They noted that due to the structure of the molecule, an “embryo-toxic effect” (p124) was possible. They refused a licence. In the USA, Dr Frances Kelsey resisted significant pressure from the prospective American licensee company (Richardson Merrell) and managed to delay the approval of the drug until it was removed from sale in 1961. Her delay meant that only around 160 babies are estimated to have been affected by thalidomide in the USA. What these countries show is that the toxic properties of thalidomide were possible to identify using the technologies and processes of the time. Those governments which failed to prevent the distribution of thalidomide are partly to blame for the disaster, and should also be held to account.

 

In 2019, the generation of thalidomide survivors is turning 60. What “The Thalidomide Catastrophe” makes clear is this: the international sale of the drug was preventable. Its risks should have been identified by the company which patented the drug, those which distributed it and by the governments which allowed its sale. The damage which was initially caused has been extended over six decades by a failure to acknowledge and apologise for the harm that was caused. The need for an apology remains.

Reflective practice groups for liaison psychiatry nurses: are they helpful? Our study

Liaison psychiatry nurses have a tough job. They are based in the Emergency Department and work with individuals experiencing acute distress; these patients may have recently self-harmed or attempted suicide and could be at high risk of further harm. Liaison psychiatry nurses contact gatekeepers to other services while under the pressure of national waiting-time targets. They usually have no continuity with patients after they are discharged and may be left wondering how their patients’ situations turned out in the end. Both mental healthcare staff and emergency department staff are high risk groups for burnout (Johnson et al., 2018; Potter, 2006); liaison psychiatry nursing combines each of these elements and so these nurses may experience particularly elevated stress.

In order to provide liaison psychiatry nurses with more support, one hospital introduced reflective practice groups. The groups were a protected hour: the liaison psychiatry nursing team left the department to go to a quiet room in another building where they could not be contacted. The groups were facilitated by a clinical psychologist already employed by the hospital. I particularly liked this feature; too often I hear about outside consultants being paid hefty sums to deliver wellbeing packages with hazy evidence bases, when most healthcare organisations already have a group of highly trained professionals employed in their  psychology department who can do this work. The psychologist enabled dialogue between the team members and facilitated their conversation but did not impose an agenda.

When I was invited to contribute to the evaluation of this intervention I was delighted. We interviewed 13 liaison psychiatry nurses who had attended the group. They identified four main benefits of participating:

  • Sharing and learning. Participants found that sharing their experiences in the group helped them to feel less alone. They realised that other people in their team were experiencing similar challenges and they left the group sessions feeling clearer-minded and lighter.
  • Grounding and perspective. Participants said the group allowed them to take a step back and gain perspective on the difficulties of their work and the risks involved. It reminded them of the value their work has.
  • Space. Participants described the group as a safe space; they felt able to ask for help or to say they were unsure of things and seek advice from their colleagues.
  • Relationships. Participants said the group supported some positive interpersonal experiences between team members. The fact that they had an external facilitator and were guaranteed to be free from interruptions led them to feel they could raise difficult issues with their colleagues, in the knowledge they would be able to resolve these before the conversation ended.

It should be noted that not all nurses found the group beneficial. Some felt that the types of discussions they had during reflective practice were already happening elsewhere and they believed a protected space was not necessary. However, these nurses recognised that some of their colleagues benefited from the group, and were willing to participate in recognition of the overall team benefit.

We weren’t able to quantitatively evaluate the group as the number of participants in the study was too small. However, our qualitative data suggested that overall these groups provided a range of benefits which would have been hard to get from another forum, and some participants believed that sickness absence in the team would have been higher without them.

Practical tips for running reflective practice groups

For anyone wanting to run reflective practice groups, our study suggested a few things should be considered:

  • Groups shouldn’t include managers. The presence of managers changed the nature of the group and inhibited open discussion.
  • Protected time is key. Nurses stated that the groups were the only time they were guaranteed to have a conversation at work without interruption, and this was an absolute necessity for helping them feel able to discuss sensitive issues.
  • The facilitator must be external to the group. Previous research suggests nurses trained in reflective practice can supervise these groups and there can be benefits to having someone of the same discipline provide this facilitation. However, experienced clinical psychologists should be sufficiently trained to offer this in the absence of trained nurses. Our study suggests this is acceptable to nurses and the important thing is that the facilitator works in healthcare but is external to their team.

A practical and cost-effective solution

Further research is needed to establish the effectiveness of reflective practice groups for supporting staff wellbeing. However, the evidence base for burnout reduction interventions in general is still small (see my previous blog on this here), and the best methods for supporting staff are not yet established.  While we wait for evidence-based recommendations, reflective practice groups are a cost-effective form of support for liaison psychiatry nurses: they require no special equipment, no long periods of staff absence from work and can be facilitated by in-house psychologists, so no expensive outside consultants are required.

To read this study please see here


Six ways that breaking bad and difficult news in ultrasound is different to other settings

Not all pregnancies follow the textbook. Around 1 in 6 are lost to miscarriage or stillbirth and in 1 in 20 there is an unexpected finding on an ultrasound scan which could suggest the baby has a health condition (Ahman et al., 2014; Blohm et al., 2008; Skupski et al., 1996). Altogether around 150,000 families in England and Wales are affected by one of these complications each year (ONS; 2016). These events are deeply upsetting; parents who experience them are at higher risk for depression, anxiety and even symptoms of trauma (Blackmore et al., 2011; Cumming et al., 2007; Korenromp et al., 2005).

The role of ultrasound

Ultrasound is an important tool for diagnosing these complications and in the UK sonographers are the first to break the news to parents about what they have found. The way this is done is important, as it has a strong emotional impact on expectant parents (Bijma et al., 2008; Johnson et al., 2018). However, there is currently no evidence-based training to support sonographers with news delivery. The training which is available is generally based on research which has been conducted in oncology and other healthcare settings.

The need for an evidence-based training intervention

When I have suggested that new research is needed to understand how bad and difficult news can be better delivered via ultrasound, one question I have been asked is whether this is really needed. Isn’t there plenty of research in other settings to inform training? In this blog, I will present six ways that breaking bad and difficult news via ultrasound is different to breaking bad news in other settings.

1. There is no time for sonographers to prepare before delivering the news

A large body of research tells us that expectant parents study the sonographer’s face as they do the scan: they are attuned to their body language and facial expression and quickly sense when something is wrong. The sonographer is unintentionally communicating news before they even speak, and they have no time alone at all to mentally prepare before sharing what they have found with parents. In cancer care, this would be the same as a doctor having to open test results, read and interpret them while the patient watches them.

2. Having a baby isn’t primarily a healthcare event, it’s a rite of passage

Few people will spend years thinking about their future with a diagnosis of cancer, but many people, consciously or subconsciously, gather quiet expectations about what their future will be like with a child. When you deliver difficult news as a sonographer, you deliver it into a world of positive expectation, which is further fuelled by people sharing scan pictures on social media, and television shows like One Born Every Minute. Because of this, the situation is particularly high stress for both those delivering and those receiving the news.

 3. The need for a second opinion

When a sonographer identifies a miscarriage, stillbirth or fetal anomaly a second opinion is necessary to confirm his. The sonographer needs to leave the scan room to find another qualified healthcare professional who can confirm what has been seen. This is a difficult point, and one that is not encountered in other areas of healthcare. Sonographers are often torn over how much to disclose to the expectant parent before the second opinion has been gathered, especially if they are not confident themselves in what they have seen. Failing to disclose their concerns to the parent can result in parents feeling anxious when they find a second professional has been invited into the scan room without explanation. However, immediately disclosing concerns to parents that are then not confirmed can cause unnecessary anxiety. It’s a dilemma that sonographers regularly face which is not found in other difficult news delivery scenarios.

4. The news may be uncertain

When receiving difficult news in other settings, patients can rightly expect that the healthcare professional telling them this news will be informed about their condition and be able to provide detailed information on this. However, sonographers do not have this luxury. While scanning technology has advanced significantly in the last few decades, it is not always possible to provide accurate diagnoses and prognoses immediately. Because of this, sonographers are often communicating difficult news which is uncertain, and which could change in light of subsequent investigations.

5. Ultrasound presents opportunities and raises challenging choices

Unlike other areas of healthcare, ultrasound often provides a diagnosis before anyone’s health has been compromised. It can enable expectant parents to have missed miscarriages diagnosed and allow them to choose whether they want to shorten the length of their pregnancy by accepting a medical intervention. Ultrasound can also detect some fetal abnormalities.  If a baby is found to have a disability (or a possible disability) parents may need to decide whether to have invasive testing; whether to terminate the pregnancy; or in rare cases, whether to have prenatal interventions. These kinds of decisions introduce a huge weight of responsibility – could prenatal investigations and interventions put the baby or mother at risk? Is it morally wrong to terminate a pregnancy? Will not terminating a pregnancy detract energy from any existing children? When sonographers deliver difficult news they know they are often placing a burden of responsibility on expectant parents to make choices, in a way that is not encountered elsewhere in healthcare.

6. The warning shot is not always wanted

Most models for breaking bad news recommend the delivery of a ‘warning shot’ before the main news is imparted (e.g., Baile et al., 2000). This is designed to prepare patients that bad news is coming, and might run like this: “I’m afraid we have identified some concerning findings in your results”. My research has identified that this warning shot is not always wanted in ultrasound settings because parents have already received their warning shot from the sonographer’s body language and facial expression (see my blog on parent experiences here). These kinds of warning shots only extend the overall duration of the event and serve to increase expectant parents’ anxieties.  Furthermore, if the news being delivered is that the baby has a disability, this kind of warning shot can be taken as a negative value judgement by the healthcare professional, which may offend the expectant parent. Instead, parents prefer to be told things directly but kindly, in simple language. In my previous study in parents of children with limb differences, parents most preferred it when healthcare professionals simply said something like: “I can’t currently see your child’s arm below the elbow” (Johnson et al., 2018).

Summing up

There is strong evidence from other healthcare settings that training to improve news delivery is highly effective (see my blog on this here). However, there are clear differences between breaking bad and difficult news in ultrasound compared with other settings. Assuming that the same principles can be transposed from other healthcare settings into ultrasound without adaptation could at best reduce the effectiveness of training, and at worst, increase parental anxiety.

Tackling burnout in UK trainee doctors is vital for a sustainable, safe, high quality NHS: Our letter to the BMJ

In 2018, for the first time, the General Medical Council (GMC) included items on burnout in its National Training Survey. The survey was completed by 51,956 trainee doctors and 19,193 trainers, making it the largest burnout survey in UK doctors to date. The response rate was also extremely high – 96% of all doctors in training who were contacted completed it, as did 41% of all contacted trainers. As such, these results provide a reliable picture of the current situation in the medical workforce. The survey found that 24% of trainees and 21% of trainers feel burnt-out to a high degree or a very high degree (for the full report, see here).

When I read these results in the BMJ, I wasn’t surprised. Rates of stress and burnout are high in healthcare staff internationally; in the 2018 Medscape report on physician burnout and depression, out of 15,000 US doctors, 42% were burnt-out and 12% were categorised as ‘colloquially depressed’. I was also concerned: a growing body of research shows a strong and consistent link between higher staff burnout and poorer patient care. Papers I have authored and co-authored show:

• 70% of studies which have investigated burnout and patient safety in healthcare staff have found a significant link between the two (Hall et al., 2016).
• In nurses, higher burnout is linked with poorer perceptions of patient safety both at the level of the individual practitioner and the ward level (Johnson et al., 2017).
• GPs think that burnout affects the quality of patient care by reducing their abilities to emphathise, to show positive attitudes to patients and by increasing the number of inappropriate referrals made (Hall et al., 2017).

Together with Dr Maria Panagioti and Dr Christopher Bu, I decided to respond to the BMJ article on the survey findings to highlight the evidence that burnout in doctors affects patient care. In particular, our letter focused on a recently published systematic review and meta-analysis led by Dr Panagioti. The findings of the review are described in more detail in a previous blog post (see here), but in brief, the review reported that burnt-out doctors are at twice the risk of being involved in a patient safety incident and at twice the risk of having dissatisfied patients.

This research reinforces the importance of measuring burnout in the medical workforce and the need to reduce this. The best way to intervene is currently unclear; while evidence suggests that interventions which target organisations (for example, redesigning jobs) are more effective than those which target individuals (for example, delivering mindfulness courses; Panagioti et al., 2017), there are many interventions which blur this boundary. These include training interventions, which are delivered to individual practitioners but aim to support them in their work, rather than improve their personal coping skills. Evidence suggests these are effective for tackling burnout (Dreison et al., 2018). Clearly, more research is needed. However, while we wait for this, I would suggest that organisations respond to the expressed needs of their workforce, providing the interventions that are both requested and well utilised.

To read our letter to the BMJ, please see here.

To read my previous blog on tackling burnout, please see here.

Burnout in doctors and the quality of patient care: Our systematic review

There is increasing evidence that healthcare staff burnout is linked to a range of negative outcomes, including increased staff absences, higher rate of staff turnover, and poorer quality of patient care (see my previous blog on this here). In a systematic review I co-authored, we found that that 21 out of 30 (70%) studies looking at the link between higher staff burnout and poorer patient safety reported a significant association between the two (Hall et al., 2016). The review found hard evidence for what many clinicians could see happening in their wards and surgeries: when staff are hard pressed, patient care suffers. It was well received on social media and has since been cited dozens of times.

However, while this previous review found clear evidence for a link between staff burnout and patient safety, it seemed to me that two questions remained unanswered. The first was whether there is also a link between burnout and other aspects of patient care, such as patient satisfaction. The second was what the strength of this relationship is: that is, just how much do increases in burnout impact patient care?

So, when I was invited to contribute to a systematic review on the links between burnout and patient care in doctors by Dr Maria Panagioti, I jumped at the chance. The review led by Dr Panagioti aimed to answer both these questions. It gathered studies which investigated burnout in doctors in relation to a broader range of outcomes, including:

  1. Patient safety incidents, (e.g., adverse events, medication errors, diagnostic incidents)
  2. Low professionalism (e.g., adherence to treatment guidelines, quality of communication, malpractice claims, empathy)
  3. Low patient satisfaction

It also quantified the strength of these relationships using meta-analysis, which was not employed in the previous review.

Is burnout linked with patient safety incidents?

The review identified 21 studies which reported on the association between burnout and patient safety incidents. The results of the meta-analyses suggested that burnt-out doctors were twice as likely to be involved in a patient safety incident as those not suffering from burnout. All aspects of burnout (exhaustion, disengagement and low accomplishment) were associated with a significantly higher risk of being involved in a patient safety incident.

Is burnout linked with low professionalism?

28 studies were found which reported on the link between burnout and low professionalism (e.g., showing low empathy, having received a malpractice claim). The results of the meta-analyses suggested that burnt-out doctors were twice as likely to show low professionalism. When the different aspects of burnout were examined separately, disengagement was the aspect most linked with low professionalism. Doctors who were disengaged from their patients were 3-times as likely to exhibit low professionalism. Doctors high in emotional exhaustion or low in personal accomplishment were over 2.5-times as likely to exhibit low professionalism.

Importantly, the review found that the link between burnout and low professionalism was twice as high in trainee and early career doctors compared with more experienced doctors. This is particularly concerning when the recent GMC survey results showing that a quarter of trainee doctors are burnt-out are considered.

Is burnout linked with low patient satisfaction?

7 studies reported measures of patient satisfaction. It was found that burnt-out doctors were at twice the risk of having dissatisfied patients. Again, disengagement was the aspect of burnout most closely linked with low patient satisfaction, with disengaged doctors showing a 4.5-fold increased risk. Low personal accomplishment was also linked with twice the risk of low patient satisfaction. No link was found with emotional exhaustion.

Where now?

This review finds strong evidence that burnt-out doctors are at significantly higher risk of being involved in patient safety incidents, showing low professionalism and having dissatisfied patients. Having clarified the presence and size of the problem of burnout for patient care, the next step for us as researchers is to identify evidence-based solutions to this problem. While a number of interventions to reduce burnout have been proposed (see Panagioti et al., 2017), there is a need to identify 1) which interventions are most feasible and most effective, and 2) whether reducing burnout can improve patient care.

For my previous blog on tackling burnout, please see here.

The review described in this article was published in JAMA: Internal Medicine. To read it, please see here.