ethics and integrity

Question 1

history ethics: Nürnberg code

Answer 1

• Nürnberg code 1947
• reaction on medical experiments during WW2
• 10 ethical principles:
  1. participation is voluntary
  2. leads to information that is of value for society
  3. no unnecessary damage (physical/mental)
  4. informed consent
  5. always allowed to stop

Question 2

history ethics: declaration of Helsinki

Answer 2

• declaration of Helsinki 1964 (current 2013 version)
• by World Medical Association (medical research)
• most important issues:
  1. patient interest is primary concern
  2. participation is voluntary & informed consent is necessary
  3. design of study needs to be adequate
  4. results need to be published (at least knowledge you gain should be available to other people in the world)

Question 3

laws

Answer 3

• different laws in different countries based on Helsinki declaration
• about medical experiments on humans
• in the Netherlands: WMO
• one governmental body oversees this: CCMO
• CCMO has delegated part of its responsibilities to local Medical Ethical Committees (METc)
• experiments have to be reviewed by Medical/ Ethical commitees
• in more complicated cases: reviewed by the central body itself

Question 4

When is something a medical experiment?

Answer 4

according to Dutch law:

• which is medical-scientific in nature AND
• in which participants are subjected to tests that threaten their integrity and/or are imposed to behave in a certain way

= all RCTs with patients aimed at improving health

Question 5

What does this mean for your study?

Answer 5

• principal investigator: BROK (certification on laws and ethics)
• RCT proposal needs to be approved before the first patients (by Medical Ethical review board)
• might take a long time (6 months) to be approved
• it might mean that certain designs are not possible:
  1. to withhold patients from treatment
  2. not to create waitlist for treatment
  3. to include suicidal patients
  4. informed consent needs to be written on paper (not online)

Question 6

what does the METc require?

Answer 6

• numerous documents:
  1. research protocol (SPIRIT based)
  2. patient information (informed consent, information folder, advertisement)
  3. medical device forms
  4. risk classification (and insurance)
  5. data safety monitoring board
  6. contract with grant body
  7. CV independent doctor
  8. CV of the principal investigator
• ABR form (general review and registration form)

Question 7

medical device

Answer 7

• instrument used for health including internet programs/ apps
• 3 different laws
• CE marking = fulfills requirements of safety (EU)
• for both: investigational medical device dossier (IMDD)

Question 8

IMDD

Answer 8

• includes items about the manufacturer:
  
  • providing permission to use and information on safety
  • manufacturer reports study to inspectorate

Question 9

risk classification

Answer 9

• small/ moderate/ large chance to cause slight/ moderate/ severe damage
• -> negligible/ moderate/ high risk
• insurance needed unless negligible risk (patient insurance and you have to provide information to the patient about that)
• high risk: data and safety monitoring board required: meeting on a regular basis and see how you handle patients and data, otherwise optional

Question 10

METc

Answer 10

• do not start before approval
• report (within expected limits)
  
  • serious adverse events
  • suspected unexpected serious adverse reaction
  • serious adverse device effect
    (also when not related to your study, cause if it happens in multiple patients, it might actually be related)
• if anything changes in protocol
• general report to METC: every year –> &at the end

Question 11

integrity

Answer 11

• your own behavior as a researcher

- umbrella organization of universities in the Netherlands: code: principles that researchers need to follow

Question 12

code: honesty and scrupulousness

Answer 12

1. honest and fortright
2. perform scrupulously
3. unaffected by the pressure to achieve

Question 13

code: reliability

Answer 13

1. support and strenghten the fundamental reliability of science

Question 14

code: verifiability

Answer 14

1. information is verifiable

2. it is made clear what the data and conclusions are based on

Question 15

code: impartiality

Answer 15

1. practitioners are led by no other interest than academic interest

Question 16

code: independence

Answer 16

1. academic freedom and independence (not organization who developed a treatment…)

Question 17

code: responsibility

Answer 17

1. responsibility for the societal implications of their work

Question 18

what can go wrong?

Answer 18

rare:
1. fraud
2. plagiarism 
more normal:
1. authorship
2. p-hacking/ selective outcome reporting
3. making mistakes, being sloppy

Question 19

what can go wrong? authorships

Answer 19

rules for being a co-author

Question 20

confirmation bias

Answer 20

looking for data that confirms hypothesis, e.g., scale of graph in a specific way

Question 21

bias in RCT

Answer 21

RCT is done to prevent bias

• but design carefully
• still many opportunities for bias:
  1. confirmation bias
  2. researcher allegiance

Question 22

researcher allegiance

Answer 22

researchers in favor for a treatment/ developed it themselves find higher effects than in replication studies that don’t have a tie to the treatment

Question 23

what does that mean for your research?

Answer 23

1. work according to integrity principles
2. use SPIRIT/CONSORT
3. take BROK exam
4. publish protocol
5. discuss authorship early
6. when you suspect integrity issues: VU integrity officers