Members Evidence Request - Supporting Clinical Practice

The Clinical Effectiveness Unit (CEU) provides an evidence-based enquiry service for FSRH members. The CEU will conduct a literature review and summarise the available evidence in relation to a particular medical condition and/or contraceptive method.


Recent Questions and Answers that have been submitted to the CEU can be seen below. Please note, the full answer includes references to more information and guidance.

The FSRH CEU has produced a quick guide on conducting systematic literature reviews to answer clinical questions (log in to access the guide). This brief and easy-to-use guide aims to support FSRH members to conduct a systematic literature search/review to answer clinical enquiries they may have. The process described in this guidance is adapted from the process used by the FSRH CEU when responding to enquiries made via the members evidence request service.

How to Submit a Members' Evidence Request

How do I get access to the Members' Evidence Request?

  • please log in to ‘My FSRH’ and
  • click on ‘Members' evidence request’ to search for questions or submit your own question.

This service is available to current FSRH members (Diplomates, Associates, Members, Fellows). 

I haven't set up a log in yet - what should I do?

If you are an FSRH member and have not yet created your ‘My FSRH’ account, please click the ‘Register’ button on the top right of this website and follow the steps to gain access to your account. Please use an email address that we will have contacted you on previously.

Once you have registered you will be able to access the full service and search the database as shown in the video. 

 

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Example Question One

Regarding self administration at home of sayana press for someone who was starting an injectable for the first time - how safe is this (in relation to anaphylaxis) to be done at home for women who have not already had DMPA or sayana (bearing in mind anaphylaxis can sometimes only manifest itself after the second injection)?

Response: 
Anaphylaxis is an acute, systemic, potentially life-threatening immediate hypersensitivity reaction, involving the release of mediators from mast cells, basophils and recruited inflammatory cells. Anaphylaxis is defined by a number of signs and symptoms, alone or in combination, which occur within minutes, or up to a few hours, after exposure to a provoking agent. Most cases are mild but any anaphylaxis has the potential to become life-threatening. Severe initial symptoms develop rapidly, usually reaching peak severity within 3-30 minutes. Observation for at least 1 hour is required to ensure that a mild reaction is not progressing.[1,2]

Anaphylaxis may occur as a result of immunologic mechanisms (either IgE-dependent or IgE-independent), or non-immunologic mechanisms. Immediate onset hypersensitivity including anaphylaxis has been reported for a wide range of drugs. [1] The mechanism underlying anaphylactic reaction to DMPA injection (whether to MPA itself or an excipient) is not evident from the published literature.

The Summary of Product Characteristics (SPC) for Sayana® Press lists risk of anaphylactic response as ‘not known’ (cannot be estimated from the available data).[3] It notes “As this product contains methylparahydroxbenzoate [E218] and propylparahydroxbenzoate [E216], it may cause allergic reactions (possibly delayed), and exceptionally, bronchospasm.” The SPC for Depo-Provera® states “Reports of anaphylactic responses (anaphylactic reactions, anaphylactic shock, anaphylactoid reactions) have been received” and lists anaphylactic reaction as a “rare” adverse reaction (≥ 1/10,000 to < 1/1000).[4] Depo-Provera also contains methylparaben (E218) and propylparaben (E216) - they are present in cosmetics and medicines to which individuals could have had prior exposure and be sensitised if IgE-mediated reaction was the mechanism of reaction.

The FSRH CEU identified no further data to further inform the risk of anaphylaxis associated with administration of Sayana Press or Depo Provera. As of 01/06/2020 (all reports processed from inception up to 30 April 2020), the Interactive Drug Analysis Profiles (iDAP) on Medicines and Healthcare products Regulatory Agency (MHRA) Yellow Card scheme website lists 94 reports of “anaphylactic reaction”, 13 of “anaphylactic shock” and 10 of “anaphylactoid reaction” for all medroxyprogesterone acetate (MPA)-containing drugs.[5] Listing of an adverse event in a DAP does not, however, confirm that the active drug or any of the product excipients caused the effect.

FSRH CEU literature review identified four published cases of anaphylaxis following IM depot medroxyprogesterone acetate (DMPA) injection. A 16-year-old girl had an anaphylactic reaction shortly after administration, having previously received four doses of DMPA with no reaction.[6] A 40-year-old woman with no previous apparent exposure to exogenous progestogen suffered an immediate anaphylactic reaction to a DMPA injection given at the time of surgical abortion; she had a similar response to repeat injection 12 weeks later.[7] Two older cases from 1993 and 1974 are also reported. [8,9] No published cases of anaphylactic reaction following administration of Sayana Press are identified.

Conclusion:
Reported cases suggest that anaphylactic reaction has occurred with both first and subsequent exposures to IM DMPA. The provoking agent and mechanism for the response is not apparent . It is assumed that anaphylactic response could also be possible with both first and subsequent exposures to Sayana Press. In line with advice in the SPC for Sayana Press [3], individuals with known sensitivity to any excipient should not use the product. Self-administration of Sayana Press should be taught by a healthcare practitioner, but it is accepted practice that the product can be self-administered by the individual at home. The risk of anaphylactic reaction appears to be very low, however the FSRH CEU suggests that users can be advised to ensure that there is a competent adult present at the time of administration who is aware that they should call for emergency help at the time of onset of any relevant symptoms (see “Symptoms and Signs of Anaphylaxis” below).

Symptoms and Signs of Anaphylaxis[1,2]

The initial manifestation of anaphylaxis may be loss of consciousness. Patients often describe "a sense of doom." In this instance, the symptoms and signs of anaphylaxis are isolated to one organ system, but since anaphylaxis is a systemic event, in the vast majority of subjects two or more systems are involved.

  • Gastro-intestinal: Abdominal pain, hyperperistalsis with faecal urgency or incontinence, nausea, vomiting, diarrhea.
  • Oral: Pruritus of lips, tongue and palate, edema of lips and tongue.
  • Respiratory: Upper airway obstruction from angioedema of the tongue, oropharynx or larynx; bronchospasm, chest tightness, cough, wheezing; rhinitis, sneezing, congestion, rhinorrhea.
  • Cutaneous: Diffuse erythema, flushing, urticaria, pruritus, angioedema.
  • Cardiovascular: Faintness, hypotension, arrhythmias, hypovolemic shock, syncope, chest pain.
  • Ocular: Periorbital edema, erythema, conjunctival erythema, tearing.
  • Genito-urinary: Uterine cramps, urinary urgency or incontinence.

C: Evidence-Based Medicine Question (which guided our literature search strategy)

Population:  Women of reproductive age
Intervention:  Progestogen-only injectables
Outcome: Anaphylactic reaction

Log in to read the full response and list of references.

Example Question Two

Please can you explain why it is OK to use a Nexplanon for 4 years and Mirena for 6 years during Covid-19 but not under normal circumstances?

Response:

The risk of pregnancy during one additional year of use of Nexplanon and the 52mg LNG-IUS is likely to be small (as indicated by the available evidence), but we do not know for certain that it is as low as that during the licensed duration of use.

There is inadequate evidence to recommend this as standard practice in “normal” times as women expect extremely low failure rates from LARC. We note that effectiveness may still be greater than with user-dependent contraceptive methods (further studies are required to confirm this) and that extended use is standard in some parts of the world (where, for example individuals have limited access to contraception or pay a lot of money for it).

This comes down to a balance of risk and benefit at all times: At a time when there is a significant risk of coronavirus transmission associated with medical procedures, any small possible risk of pregnancy during a year of extended use is considered to be outweighed by the benefit of avoiding virus transmission.

However, FSRH guidance has been clear that contraceptive effectiveness cannot be guaranteed during this time and that women may wish to use additional contraceptive precautions.

In "normal" times in the UK, when LARC replacement is not associated with significant risk of virus transmission, the benefit of achieving extremely effective contraception by replacing the LARC at the end of the licence is likely to outweigh the risks associated with replacement (certainly until we have more study evidence).

Thus, at times other than during the current pandemic, FSRH advice will be that Nexplanon should generally be changed after 3 years and the 52mg LNG-IUS at 5 years (except in older women).”

In summary, because of different risk/benefit balance, slightly differing guidance may be applicable to different situations. 

Login to view the full response and reference list here. 

Example Question Three

What Covid-19 PPE requirements are there when performing manual vacuum aspiration and other SRH procedures?

Response:

In the absence of specific evidence of Covid-19 transmission associated with SRH procedures, the FSRH CEU can make no formal recommendation regarding required PPE. However, the following published guidance is identified:-

1. RCOG guidance on abortion care during the Covid pandemic [1]
The Royal College of Obstetricians & Gynaecologists (RCOG) guidance Coronavirus (COVID-19) infection and abortion care: Information for healthcare professionals indicates that:

“Unless the anaesthetic used involves ventilation, neither abortion nor obstetric procedures are classed as aerosol generating procedures which carry the highest risk of transmission of respiratory viruses.”

The RCOG guidance also notes that:

“Current evidence, based on a small number of cases, suggests that COVID-19 is not present in genital fluid, although it is too early to know whether vertical transmission is a significant risk.”

2. PHE guidance on COVID-19 PPE [2]

Public Health England (PHE) Guidance COVID-19 personal protective equipment (PPE) states:

“Health and social care workers should consider the need for contact and droplet precautions based on the nature of care or task being undertaken.

Risk assessment on the use of eye protection, for example, should consider the likelihood of encountering a case(s) and the risk of droplet transmission (risk of droplet transmission to eye mucosa such as with a coughing patient) during the care episode.

Sessional use of FRSMs and eye protection is indicated if there is perceived to be close or prolonged interaction with patients in a context of sustained community COVID-19 transmission. 

Ultimately, where staff consider there is a risk to themselves or the individuals they are caring for they should wear a fluid repellent surgical mask with or without eye protection, as determined by the individual staff member for the episode of care or single session.”

With regard to aerosol-generating procedures (AGP) specifically, the guidance states:

“The highest risk of transmission of respiratory viruses is during AGPs of the respiratory tract, and use of enhanced respiratory protective equipment is indicated for health and social care workers performing or assisting in such procedures. The evidence review will continue to be updated in light of emerging evidence for this new pathogen.”

PHE guidance indicates:

“The following procedures are currently considered to be potentially infectious AGPs for COVID-19:

- intubation, extubation and related procedures, for example, manual ventilation and open suctioning of the respiratory tract (including the upper respiratory tract)

- tracheotomy or tracheostomy procedures (insertion or open suctioning or removal) 

- bronchoscopy and upper ENT airway procedures that involve suctioning 

- upper gastro-intestinal endoscopy where there is open suctioning of the upper respiratory tract

- surgery and post mortem procedures involving high-speed devices 

- some dental procedures (for example, high-speed drilling) 

- non-invasive ventilation (NIV); Bi-level Positive Airway Pressure Ventilation (BiPAP) and Continuous Positive Airway Pressure Ventilation (CPAP)

- High Frequency Oscillatory Ventilation (HFOV) 

- induction of sputum

 - high flow nasal oxygen (HFNO)"

3. Intercollegiate general surgery guidance [3]

Updated Intercollegiate General Surgery Guidance on COVID-19. Guidance for surgeons working the pandemic states:

“Operating theatres where Aerosol Generating Procedures (AGPs) are regularly performed are considered a higher risk clinical area and full PPE is advised where COVID-19 is possible or confirmed. General anaesthesia is an AGP.”
“Laparoscopy is considered to carry some risks of aerosol-type formation and infection and considerable caution is advised. The level of risk has not been clearly defined and the level of PPE deployed may be important. Advocated safety mechanisms (filters, traps, careful deflating) can be difficult to implement.

The smoke plume at laparotomy from coagulating instruments may also not be without some risk. Given the current requirement to protect staff and other patients, a safety-first approach is needed.”

Ultimately, local policy, relevant to the current local infection risk, must be followed.

References

1. Royal College of Obstetricians & Gynaecologists. Coronavirus (COVID-19) infection and abortion care. Information for healthcare professionals. Version 2. 1 April 2020. (accessed on 15/05/2020)

2. Public Health England. Gov.uk. The Department of Health. Guidance: COVID-19 personal protective equipment (PPE). Updated 3 May 2020. (accessed on 15/05/2020)

3. Royal College of Surgeons of England. Updated Intercollegiate General Surgery Guidance on COVID-19. Guidance for surgeons working the pandemic. 7 April 2020. (accessed on 15/05/2020)

Please note: The advice given by the CEU should be considered as guidance only and is meant to be used alongside clinical judgement to guide clinical practice or policy. Questions that are a matter of clinical judgment and not evidence should be directed to local sexual and reproductive health leads.

Log in to access the full response and members evidence request here.