Modrec saps

Ministry of Defence
Schedule of Approved Procedures
Research Ethics Committee
These guidelines relate to all non-clinical research involving human participants undertaken, funded or sponsored by MOD. MoD personnel conducting non-MOD research, while attached to an organisation with its own arrangements for indemnity, ethical scrutiny and compensation, should observe local arrangements and do not require approval by the Ministry of Defence Research Ethics Committee (MODREC) for the procedures listed in this document. Paragraph 21 modified as per Mark Glover This document will be subject to version control by: Ministry of Defence Research Ethics Committee (MODREC)
CONTENTS
2. Scope of the Schedule of Approved Procedures 5. Collection of Biological Samples, Anthropometric and Simple Physiological Measurements 6. Pulmonary Function and Exercise Testing 9. Modifications to Sleep and Rest Patterns 18. Exposure to Gases & Breathing Mixtures 19. Diving and Compression Chamber Experiments 21. Helicopter Underwater Escape Training Ministry of Defence Research Ethics Committee (MODREC)
1. INTRODUCTION

If the proposed research procedures fall within the scope of the Schedule of Approved
Procedures (SAPs) and the participants are not less than 18 years old, ethical approval can be
given on behalf of MODREC by its chairman or vice-chairman following scrutiny by the
appropriate scientific advisory committee. Ex-committee approval of such protocols will be
reported at the next MODREC meeting.

2. SCOPE OF THE SCHEDULE OF APPROVED PROCEDURES

2.1
The procedures described below have been approved by MODREC. In addition, to come within the scope of the SAPs, experiments involving human participants must conform to the World Medical Association Declaration of Helsinki (2004)
(www.wma.net/en/30publications/10policies/b3/index.html).
3.
THE SCHEDULE OF APPROVED PROCEDURES
These guidelines relate to non-clinical research involving human participants undertaken, funded or sponsored by MOD. 3.2 Request can be made for a new procedure to be added to the SAPs, subject to Protocols submitted for ethical approval should state whether or not the proposed research procedures fall within the SAPs.
4.
ADMINISTRATION OF DRUGS
Proprietary drugs, approved for use by the general public by the Medicines and Healthcare products Regulatory Agency (MHRA), may be administered in doses not
exceeding those recommended and for the purposes intended by the manufacturers and
licensed by the MHRA.
The Independent Medical Officer (IMO) is to question volunteers specifically about drug
sensitivities and to exclude from a study those (s)he considers may be hypersensitive to the
drugs to be used.
5.
COLLECTION OF BIOLOGICAL SAMPLES, ANTHROPOMETRIC AND
SIMPLE PHYSIOLOGICAL MEASUREMENTS
The following procedures may be used by Medical and Non-Medical personnel with the appropriate training. Venous blood samples must not be taken from participants with a history of anaemia or who have donated blood within the preceding 3 months of the trial: a. Peripheral venepuncture to a maximum of 6 samples per day, 21 samples per seven day week with a maximum of 30 ml per sample. No more than 500 ml of blood may be taken in any 3 month period. Ministry of Defence Research Ethics Committee (MODREC)
b. Cannulation of a peripheral arm vein for the purpose of obtaining a series of blood samples, no more than 1 cannulation to be performed on the same arm per seven day week, cannulae to be inserted for a maximum of 12 hours. A maximum of 30 ml per sample, maximum of 180 ml per day. No more than 500 ml of blood may be taken in any 3 month period. c. Arterialized capillary blood sampling from the ear-lobe to a maximum of 2 samples per day, but to a maximum of 10 samples per seven day week. Use of rubefacients is permissible. d. Capillary finger-prick samples to a maximum of 10 samples per day and not e. Collection of samples of sweat, saliva, urine and faeces excreted naturally. f. Insertion of aural and rectal thermal probes and administration of gastro-intestinal g. Insertion of oesophageal temperature probes. h. Application of thermal probes to the skin surface. i. Application of ECG, EMG, EOG and EEG electrodes to the skin surface. j. Measurement of body dimensions when natural movements are allowed (e.g. stature when standing on tiptoe as opposed to standing with both feet on the floor, measurement of reach envelopes etc.) l. Electrical nerve conduction measurements of upper and lower limbs using surface m. Blood flow and volume measurements using strain gauge and plethysmographic n. Transcutaneous oxygen and carbon dioxide measurements in accordance with p. Flow measurement of inspired and expired gas, collection and sampling of expired gas using low resistance mouthpiece valve and tubing. q. Measurement of thermal sensory thresholds using purpose-built non-invasive equipment in accordance with manufacturers' recommendations. r. Blood pressure measurement by non-invasive methods. Ministry of Defence Research Ethics Committee (MODREC)
s. Magnetic Resonance Imaging (MRI) may be performed by scanning in accordance with the hospital’s safety precautions. t. Measurement of cerebral blood flow using ultrasonic transcranial Doppler in accordance with recognised safety standards. u. Detection of venous gas emboli by ultrasonic Doppler at recognised external sites in accordance with recognised safety standards. v. Measurement of work of breathing and lung volumes by Respiratory Inductance y. Low risk non-invasive procedures, at the discretion of the MODREC chairman or PULMONARY FUNCTION AND EXERCISE TESTING
The following procedures may be used by Medical and Non-Medical personnel with the appropriate training. Procedures 6.1 (h) to 6.1(j) must not be carried out by participants with a history of anaemia or who have donated blood within 3 months of the trial: a. Air flows, airways resistance and lung volumes by spirometry, whole body b. Transfer factor by TLCO single breath, intra-breath and re-breathing methods. c. Salbutamol inhalation and exercise and cold air challenges. d. Insertion of oesophageal balloons and recording probes. e. Assessment of respiratory drive by the Read rebreathing technique. f. Mixed venous PCO2 assessments by re-breathing methods. g. Use of marker gases at non-toxic concentrations for gas uptake and dilution studies for measurement of lung and body compartments. h. Ergometry (treadmill, cycle, step test, surface and underwater in flumes or against swimming machines), together with associated measurements of ventilation and gas exchange from expired air collected through a mouthpiece. Exercise to exhaustion and VO2max procedures are permitted only following appropriate medical screening and when a designated medical officer (current in resuscitation procedures) is within the building. ECG recording and monitoring (by an investigator trained in ECG interpretation) will be conducted throughout this procedure. Resuscitation equipment Ministry of Defence Research Ethics Committee (MODREC)
which must include a cardiac defibrillator, oxygen resuscitator and appropriate resuscitation drugs must be immediately available. i. Best time runs, swims (surface and underwater) in the field. The following additional safety criteria will be employed with all exercise testing: a. For climatic chamber experiments, heart rate and ECG will be monitored (by an investigator trained in ECG interpretation) whilst a participant is being exposed to the heat. The participant will be withdrawn from the chamber if any of the following criteria are met: A heart rate in excess of the heart rate measured at the point of the participant’s VO2max during a previous assessment. Note that this may not necessarily be the same as the participant’s heart rate at maximal workload. Where maximum heart rate has not been measured then this should be estimated as 220 minus the participant’s age. The appearance of any cardiac dysrhythmias or ectopics at a frequency of more than 5 per minute or coupled ectopic beats. The ECG becomes unreadable for any reason (but see note 1). If the participant collapses, complains of breathlessness, nausea, dizziness or chest pain or becomes mentally confused. If the participant wishes to leave the chamber they will be permitted to do so. If the participant is willing to remain in the chamber but wishes to rest they will be permitted to do so.
7. LASER DOPPLER RHEOMETRY
7.1
The following procedures may be used by Medical and Non-Medical personnel with a. Laser Doppler rheometry to measure red cell velocity, blood flow and other variables using commercially available laser Doppler systems, operating within approved laser safety rules. 1 If the participant is clearly unstressed, then attempts will be made to rectify the problem prior to removal of the participant. Ministry of Defence Research Ethics Committee (MODREC)
b. Use of an air plethysmograph on a single digit and the application of air at a negative pressure not more than 60 mmHg below atmospheric pressure. c. Iontophoresis of healthy normal skin using a charge not exceeding 150 millicoulombs (maximum current 249 microamps). A commercially available system which complies with human use electrical standards should be used (in particular completely electrically isolating the iontophoresis electrodes from mains AC supplied), with solutions of idazoxan hydrochloride, prazosin hydrochloride, phentolamine mesylate, acetylcholine and sodium nitroprusside. d. Application of local anaesthetic cream (e.g. EMLA) in accordance with the PSYCHOLOGICAL EXPERIMENTATION
In no case will stimuli exceed safety limits defined in Standards and Legislation currently in force. Conduct of work in these areas is subject to the Code of Ethics and Conduct, issued by the British Psychological Society and include: a. Measurement of manual dexterity using laboratory tests and military tasks. b. Assessment of performance and vigilance using a range of tests designed to identify and quantify changes in sensory and central nervous system function. Tests may be presented in writing, on visual displays, aurally or by specialist equipment (e.g. for vibro-tactile assessment). Participant responses may be made in writing, verbally or through a mechanical or electronic interface. c. Additional procedures for the measurement of performance, specific aptitude, ability The use of computers to present psychomotor tasks, tests of simple and choice response time, tests of higher mental function and educational achievement and tests of vigilance. These involve the presentation of visual or auditory stimuli with participant response being manual or verbal. The use of standard paper and pencil tests of intelligence and paper and pencil versions of the types of test given in i). The use of personality tests. These may be either standard tests (such as the EPQ and 16PF) or tests of personality developed specifically by the MOD. The use of locally developed inventories, check lists and questionnaires for the assessment of attitude, mood and subjective well being. The use of in-service or experimental task simulators to provide human performance data. Ministry of Defence Research Ethics Committee (MODREC)
d. Questionnaire surveys, interviews and focus group discussions. MODIFICATIONS TO SLEEP AND REST PATTERNS

10. NUTRITION

10.1
Participants may be deprived of all food and water for up to 24 hours, providing they are fully hydrated prior to the study, their activity levels are low and the climate is sufficiently mild to enable thermoregulation to occur without active sweating. Participants may be restricted to a daily intake not less that 400 Kcals (of which the majority will be carbohydrate) and 500 ml water for periods not exceeding 10 days, subject to the activity and thermal restrictions given at 10.1. Any repeated restriction will only be applied once participants have fully rehydrated and re-established a normal metabolic state. 10.3 Supplementation of the diet is permissible providing that any nutrient substance administered is considered a foodstuff and not reported to have harmful effects in the quantities proposed (for the purposes of this section alcohol is excluded, vitamins and minerals are included). Supplementation with sodium bicarbonate at an ingested dose of up to 300mg/kg of body weight per day is also permissible. 10.4. Modification of the diet by manipulation of the relative fat, protein and carbohydrate composition is permissible for periods up to 8 weeks providing that carbohydrate provides at least 25% of the energy. 10.5. Non-radioactive (stable) isotopes may be given in a chemical form naturally occurring in the body at concentrations which do not exceed 10% of the body's content of that chemical. (Note: these isotopes are generally in the form of water or simple amino acids). EXPOSURE TO NOISE & VIBRATION
Exposure to noise limits are to be those set by The Control of Noise at Work Regulations 2005 (CNAWR). Participants may be exposed without protection, in air at sea level, to noise up to sound pressure levels (SPL) corresponding to an eight-hour equivalent LEP,d of 85 dB(A) provided that peak SPL does not exceed 137 dB(C). Exposure to vibration limits are to be in accordance with The Control of Vibration at Work Regulations 2005 (CVAWR) and the EU Physical Agents Directive on Vibration 2002 (PA(V)D). Participants may be exposed to vibrations as follows: Ministry of Defence Research Ethics Committee (MODREC)
i. an Exposure Action Value (EAV) over 8-hours (A(8)) not exceeding 0.5 ms-2 ii. an Exposure Action Value (EAV) corresponding to a vibration dose value (VDV) not exceeding 9.1 ms-1.75 in a 24-hour period (measured in accordance with International Standard ISO 2631-1 (1997)). b. For hand transmitted vibration, an EAV A(8) not to exceed 2.5 ms-2 r.m.s. (measured in accordance with International Standard ISO 5349-1 (2001)). EXPOSURE TO MOTION CHALLENGE
12.1 Participants may be exposed in a Large Motion, or other Simulator, to a motion challenge representative of a vessel at sea. The following limitations apply: a. A risk assessment of the tasks to be performed must be undertaken. b. The participant may undergo only one motion exposure of up to 90 minutes per day in one continuous session, notwithstanding short duration experimental re-starts due to equipment failure. Participants may be exposed to the arbitrary motions of any Royal Navy vessel at sea.
13. THERMAL
13.1 The schedule conforms to the Standard BS EN ISO 12894:2001 Ergonomics of the thermal environment - Medical supervision of individuals exposed to extreme hot or cold environments. 13.2 Participants with a history of anaemia or who have donated blood within the previous 1 week must not participate in trials involving thermal stress.
14. IMMERSION

14.1
Immersion experiments are subject to the following limitations. a. Irrespective of the clothing worn, water temperatures for immersion of any part of the body, or the whole body, must not exceed 42°C or be less than 0°C. b. Participants (non-divers) may be submersed (head under) breathing air from either the surface, proven re-breathing bags or from compressed air breathing apparatus for a period not exceeding 60 seconds, to a depth (to mouth) of no greater than 30 cm. c. For all experiments where there is a risk of a significant change in deep body temperature, temperature and ECG shall be monitored. For cold studies, deep body temperature is best measured by the use of a rectal thermistor sited 15 cm beyond the anus. For warm or hot studies this can, alternatively, be achieved by use of a well insulated aural thermistor. Ministry of Defence Research Ethics Committee (MODREC)
d. Exposures will be discontinued and warming or cooling (as appropriate) instigated if core temperature reaches the limits described in 15.1.c and 16.1.b. e. Monitoring of peripheral temperatures (hands and feet) will be conducted in all trials2 at environmental water temperatures below 8°C. Skin temperatures will be measured at a number of sites, to include those where the risk of cooling is greatest. f. Close surveillance is required for participants undergoing cold immersion. Exposures will be discontinued if any peripheral skin temperature falls below 8°C for more than 15 minutes continuously more than twice each day, falls below 8°C for 1 hour cumulatively in one day, or below 6°C at any time. There will be no more than two cold immersions per day for each participant. g. In addition to the above limits, in experiments lasting longer than 12 hours exposures will be discontinued and slow warming instituted if any peripheral skin temperature falls below 15° for more than 12 hours. h. The exposure limits at 14.1.e and 14.1.f shall only apply to protocols in which participants are intended to remain normally hydrated (divers who commence the exposure fully hydrated can be assumed to be normally hydrated provided that the exposure does not exceed 12 hours). Protocols in which dehydration and cold exposure are to occur concurrently fall outside the SAPs. i. Prior to commencement of any trial in which hands or feet will be exposed (without protection) to water temperatures below 15°C for more than 4 hours, or in which hands or feet (protected or not) are exposed to water temperatures below 15° for more than 12 hours all participants will be screened by infra-red thermography according to established clinical procedures. Participants who demonstrate unusual sensitivity to cold upon such screening, whether or not it is believed to result from prior cold injury, shall not be permitted to participate as participants in such trials. EXPOSURE TO COLD AIR
15.1 Participants may be exposed to cold air environments subject to the following limitations. a. Air temperatures are not below -15°C for exercising participants or -30°C for resting b. For all experiments where there is a risk of a significant change in deep body temperature, temperature and ECG shall be monitored. For cold studies, deep body temperature is best measured by the use of a rectal thermistor sited 15 cm beyond the anus. 2 Monitoring of peripheral temperatures need not be performed if the Principal Investigator can demonstrate that the clothing ensemble will ensure maintenance of temperatures above those detailed at 14.1.f. Ministry of Defence Research Ethics Committee (MODREC)
c. Exposures will be discontinued and warming instigated if core temperature falls to d. Monitoring of peripheral temperatures (hands and feet) will be conducted in all trials at environmental air temperatures below 8°C where the participant is at rest and not exercising. Skin temperatures will be measured at a number of sites, to include those where the risk of cooling is greatest. e. Exposures will be discontinued if any peripheral skin temperature falls below 8°C for more than 15 minutes continuously more than twice each day, falls below 8°C for 1 hour cumulatively in one day, or below 6°C at any time. There will be no more than two cold exposures per day for each participant. f. In addition to the above limits, in experiments lasting longer than 12 hours exposures will be discontinued and slow warming instituted if any peripheral skin temperature falls below 15° for more than 12 hours. g. The exposure limits at 15.1.e and 15.1.f shall only apply to protocols in which participants are intended to remain normally hydrated. h. Prior to commencement of any trial in which hands or feet will be exposed (without protection) to air temperatures below 8°C for more than 4 hours, or in which hands or feet (protected or not) are exposed to air temperatures below 8°Cfor more than 12 hours all participants will be screened by infra-red thermography according to established clinical procedures. Participants who demonstrate unusual sensitivity to cold upon such screening, whether or not it is believed to result from prior cold injury, shall not be permitted to participate as participants in such trials. EXPOSURE TO HOT AIR
Participants may be exposed to hot environments subject to the following limitations. a. Deep body temperature is to be monitored. b. Participants will be removed from the heat and undressed (if in protective clothing) if deep body temperature reaches 39.5°C or participants display distress or disturbed behaviour. Participants will be withdrawn if they have a high rectal temperature (= 39.5 °C), or, if on attaining a rectal temperature of 39 °C, this continues to rise at a rapid rate (defined as > 2 °C.hour-1). c. Exposure to ambient air temperatures above 80°C will only be permitted if participants are breathing dry air (normally via breathing apparatus) at 1 atmosphere absolute pressure. d. At ambient air temperatures above 80°C inspired air temperature will be measured. e. Participants will be removed from the heat if inspired air temperature reaches 80°C. Ministry of Defence Research Ethics Committee (MODREC)
f. During exposure to ambient air temperatures above 80°C skin temperatures will be measured at a number of sites, to include those where the risk of high skin temperatures is greatest. g. Participants will be removed from the heat if any skin temperature reaches 42°C or if h. The additional safety criteria detailed at 6.2 will be employed.
17. FIELD

17.1 For experiments carried out in the field and where there is a significant risk of
thermal stress but where continuous monitoring of temperatures and heart rate / ECG is not
possible, it will be permissible to use data loggers to record temperatures and heart rate. An
audible alarm will be used to signal when any of the preset limits given above are achieved.
Participants will then be withdrawn from the stressful environment.
18.
EXPOSURE TO GASES & BREATHING MIXTURES
18.1. Exposure to gases up to their Maximal Permissible Concentration (MPC – time weighted) or Occupational Exposure Limit (OEL), whichever is the higher, is permitted. Purity of breathing gases and mixtures thereof used in diving must conform to Defence Standards (DEFSTAN 68-284, or later). These standards apply to procurement, manufacture and diving on compressed air, oxygen/nitrogen and oxygen/helium mixtures. Use of any other gases or mixtures falls outside the SAPs. 18.2 CARBON a. Exposure to CO2 may be permitted up to 2kPa for periods up to 48 hours or 3kPa for b. Acute inhalation of CO2 is permitted in accordance with Read's rebreathing method c. In all other circumstances end tidal PCO2 must not exceed 8.5 kPa (65 mmHg) for 18.3 OXYGEN During manned trials in the Alverstoke Deep Trials Unit and during routine decompression procedures exposure to raised PO2 is permitted within the limits set by BR2806. PO2 may transiently exceed 200kPa (2.0 bar) during compression provided that this transient does not exceed: Exposure must be terminated immediately if either of these limits is exceeded. Ministry of Defence Research Ethics Committee (MODREC)
During open water diving inhaled oxygen partial pressure should not exceed 170kPa (1.7 bar absolute) except peaks to 2 bar absolute during descent. PO2 may transiently exceed 170kPa during compression provided that this transient does not exceed:
Exposure must be terminated immediately if either of these limits is exceeded.
18.4 Continuous exposures to PO2 in excess of 200kPa (2.0 bar) may only occur during
trials of, or trials involving, therapeutic recompression procedures. In all such cases a diving
medical officer approved by the Head of Diving & Hyperbaric Medicine, INM must be
present. PO2 must never exceed 280kPa (2.8 bar).
18.5 During diving exposures PO2 must not fall below 20kPa (0.2 bar). For non-diving
exposures PO2 must not fall below 16kPa (0.16 bar).
19.
DIVING AND COMPRESSION CHAMBER EXPERIMENTS
19.1 This part of the Schedule combines standard practice for Royal Navy operational diving with experience from experimental diving. For all sections within this part of the schedule, the limits given in the foregoing paragraphs equally apply. 19.2 For non-bell supported, non-saturation diving trials and experiments, the greatest depths and pressures permissible are: b. Oxygen/helium - 80 metres using the tables and techniques given in BR2806 or c. Air - 50 metres in water, 60 metres in compression chambers and in accordance with the air diving table (Table 11Mod) given in BR2806, RNPL 1972 tables and other tables acceptable to the HSE (the investigator is to provide proof of this). d. Nitrogen/oxygen mixtures - in accordance with the equivalent air depths given in
This is to be in accordance with the procedures described in BR2806.
20.
SUBMARINE ESCAPE & RESCUE
Personnel expected to take part in relevant experiments may be divided into two categories: Ministry of Defence Research Ethics Committee (MODREC)
a. Non-specialised submarine personnel and trainees, trained Royal Navy and Royal b. Submarine Escape Training Tank staff or personnel previously qualified as Submarine Escape Training Tank Instructors who are fully conversant with in-service equipment and techniques. Non-specialised submarine personnel and trainees, Royal Navy and Royal Marine divers. Hooded ascents may be carried out at sea by volunteers from personnel qualified in Submarine Escape but are limited to ascents from submarines at tower depths down to 31 metres and must be in accordance with current RN Standard Operating Procedures for such ascents which include the provision of on-site surface compression chambers and trained medical personnel. Such personnel are qualified to carry out a number of procedures, both at the Submarine Escape Training Tank and at sea, which are outside the limits applied to other non-specialist personnel. These may be summarised as: a. Breath-hold diving, free and buoyant ascents, and diving with breathing apparatus down to depths of 31 metres at the Submarine Escape Training Tank. b. Hooded ascents at sea from submarines at tower depths down to 30 metres. Only currently accepted escape equipment may be used for escape trials unless the following criteria have been fulfilled: a. For SETT trials, any modifications to the equipment have been in accordance with the Statement of Technical Requirement and tested in accordance with BR241 The Submarine Escape and Rescue Handbook. b. For trials at sea, in addition to the requirements of BR 241 para 23.4.a, unmanned trials to a depth of at least 10% greater than the intended trial depth have been carried out and have demonstrated that the procedure entails no greater risk than that which applies using current in-service equipment. Rates of compression and decompression during hooded escapes should be consistent with those experienced using in-service SEIE and a correctly functioning escape tower. i.e. a compression rate approximating a doubling of pressure every 4 seconds and a subsequent ascent rate of about 3 metres per second. For buoyant escapes, rate should be consistent with those experienced during submarine tank escape training. Ministry of Defence Research Ethics Committee (MODREC)
21. HELICOPTER
UNDERWATER ESCAPE TRAINING
Personnel who take part in relevant experiments will be military aircrew and other personnel who require regular helicopter underwater escape training and who have previously successfully completed tri-service helicopter underwater escape training. These personnel may undergo experimental exposures based on helicopter underwater escape training as long as the following conditions are fulfilled: the exposures take place at the tri-service helicopter underwater escape training facility at Royal Naval Air Station Yeovilton; safety and medical cover is present at least to the same level required for helicopter underwater escape training; the exposures do not exceed the depth, time, impact acceleration/deceleration and water temperature limits set for helicopter underwater escape training; the participants use either breath-hold techniques or the currently accepted in-service compressed air Short Term Air Supply System (STASS) while submerged. Ministry of Defence Research Ethics Committee (MODREC)

LIST OF ABBREVIATIONS
Control of Vibration at Work Regulations Medicines and Healthcare products Regulatory Agency Ministry of Defence Research Ethics Committee

Source: http://www.science.mod.uk/engagement/documents/modrec_saps.pdf