Editors:
Toni Belfield, consumer editor, UK
David Grimes, USA
Metin Gülmezoglu, Turkey
Frans Helmerhorst, co-ordinating editor, The Netherlands
Regina Kulier, Austria
Paul O'Brien, Ireland
Editors who left the group:
Alisson Bigrigg, UK
Michel Boulvain, Belgium
Alba DiCenso, Canada
Anne Eisinga, UK
Tina Mackie, UK
Olav Meirik, Norway
Review
Group Co-ordinator
Anja Helmerhorst, The Netherlands
Trial Search Co-ordinator
Carol Manion, USA
Web Master
Marcel Lens, The Netherlands
Senior IT Specialist
Roger Melet, The Netherlands
Junior IT Specialist
Chris Helmerhorst, The Netherlands
-
Hany Abdel-Aleem, Egypt
Rebecca Allen, USA
Miguel Arguinzoniz, Spain
Ayodele Arowojolu, Nigeria
Deborah Bartz, USA
Brandi Batchelor, USA
Katrin Ba-Thike, Myanmar
Margaret Beksinska, South Africa
Patrizia Bianchi-Movarekhi, Italy
Kelly Blanchard, USA
Kitty Bloemenkamp, The Netherlands
Lynn Borgatta, USA
Michel Boulvain, Belgium
Aldo Campana, Italy
Boonsri Chanrachakul, Tailand
Mario Chen, Costa Rica
Linan Cheng, China
Lynley Cook, New Zealand
Frances Cowan, UK
Kathryn Curtis, USA
Andrea Dalve-Endres, USA
Catherine D'Arcangues, France
Philip Darney, USA
Gabriel De Candolle, Switzerland
Justin Diedrich, USA
Beverly Draper, South Africa
Eleanor Drey, USA
Alison Edelman, USA
John Ehiri, USA
Hokehe Eko, Nigeria
Ekperonne Esu, Nigeria
Enrique Ezcurra, Cuba
Anis Fekih, Tunisia
Annabeth Fraser, USA
C.P.Gang,China
Maria Gallo, USA
Sara Garner, UK
Kristina Gemzell-Danielsson, Sweden
Anna Glasier, UK
Elizabeth Griffith, Australia
David Grimes, USA
Diederik Grobbee, The Netherlands
John Guillebaud, UK
Metin Gülmezoglu, Turkey
Vera Halpern, Russia
Jannifer Hapgood, South Africa
Cynthia Harper, USA
Jennifer Hayes, USA
Frans Helmerhorst, The Netherlands
Janet Hiller, Australia
Margaret Hoffman, South Africa
Justus Hofmeyr, South Africa
David Hubacher, USA
David Hughes, UK
LI Hui, China
Fiona Jenner, Australia
Jeffrey Jensen, USA
LaShawn Jones, USA
Jos Kleijnen, The Netherlands
Regina Kulier, Austria
Maureen Kuyoh, Kenya
Stuart Logan, UK
Patricia Lohr, USA
Laureen Lopez, USA
Nicola Low, UK
Nandita Maitra, India
Anu Manchikanti, USA
Diana Mansour, UK
Caroline Marfleet, UK
Win May, Thailand
Karen Meckstroth, USA
Suzanne Medema, The Netherlands
Olav Meirik, Norway
Anne Meremikwu, Nigeria
Martin Meremikwu, Nigeria
Stuart Morris, UK
Chelsea Morroni, South Africa
Kavita Nanda, USA
Juan Manuel Nardin, Argentina
Sara Newmann, USA
Mark Nichols, USA
Paul O'Brien, Ireland
Chioma Oringanje, Nigeria
Gilda Piaggio, Uruguay
Bert Peterson, USA
Chelsea Polis, USA
Domerudee Preechapornprasert, Tailand
Tanya Proctor, UK
Patama Promsonthi, Tailand
Asha Pun, Nepal
Elizabeth Raymond, USA
Jasper Radder, The Netherlands
Regina-Maria Renner, Switzerland
Angela Robinson, UK
Lale Say, Turkey
Kate Schaffer, USA
Sicco Scherjon, The Netherlands
Kenneth Schulz, USA
Sara Ellis Simonsen, USA
Mandisa Singata, South Africa
Jennifer Smit, South Africa
Marieke Snel, The Netherlands
Marieke Snieders, The Netherlands
Nancy Stanwood, USA
Markus Steiner, USA
Jody Steinauer, USA
Carolyn Summerbell, UK
Elizabeth Tolley, USA
Cathy Toroitich-Ruto, Kenya
Sarah Truitt, USA
James Trussell, USA
David Turok, USA
Margaret Usher-Patel, UK
Toos Van den Berk, The Netherlands
Lize Van der Merwe, South Africa
Carla Van der Wijden, The Netherlands
Nicolette Van Gemund, The Netherlands
Paul Van Look, Belgium
Clarine Van Oel, The Netherlands
Huib Van Vliet, The Netherlands
Jantien Visser, The Netherlands
Kirsten Vogelsong, USA
Dilys Walker, USA
Hajo Wildschut, The Netherlands
Shangchun Wu, China
Zou Yan, China
Mingming Zhang, China
The following people are contributing to protocols not yet
published in the Cochrane Library:
David Turok et al, USA
Misoprostol for cervical priming prior to IUD insertion in
nulliparous women
Handsearchers:
Susan Carr, UK
Nancy Graham, UK
David Grimes, USA
Nancy Kennedy, Australia
Laureen Lopez, USA
Pauline McGough, UK
Marjan Loep, The Netherlands (passed away February 2005)
Paul O'Brien, Ireland
Peer referees:
Jeff Andrews, USA
Pim Assendelft, The Netherlands
Catherine d' Arcangues, France
Richard Anderson, UK
Toni Belfield, UK
Alison Bigrigg, UK
Michel Boulvain, Belgium
Walli Bounds, UK
Peter Bowen Simpkins, UK
Lynn Borgatta, USA
Vivian Brache, Dominican Republic
Sharon Cameron, UK
Linan Cheng, China
Christine Clar, Germany
Kurus Coyaji, India
John Collins, USA
Mitch Creinin, USA
Miriam Cremer, USA
Kathryn Curtis, USA
Phil Darney, USA
Sally Davies, UK
Cor De Kroon, Netherlands
Alba DiCenso, Canada
Alison Edelman, USA
Lindsay Edouard, Canada
Jan Jaap Erwich, The Netherlands
Tim Farley, UK
Paul Feldblum, USA
Marcus Filshie, UK
Ian Fraser, Australia
Sandra Garcia, Mexico
David Griffin, UK
David Grimes, USA
John Guillebaud, UK
Metin Gulmezoglu, Turkey
Jennifer Hayes, USA
Neveen Hamdy, UK
Johan Hamerlynck, Belgium
David Handelsman, Australia
Philip Hannaford, UK
Tim Hargreave, UK
David Healy, Australia
Frans Helmerhorst, The Netherlands
Paula Hillard, USA
Justus Hofmeyr, South Africa
Kristine Hopkins, USA
Pak Chung Ho, Hong Kong
Victoria Jennings, USA
Frank Willem Jansen, The Netherlands
Jeff Jensen, USA
Ad Kaptein, The Netherlands
Nathalie Kapp, USA
Andrew Kaunitz, USA
Marc Keirse, Belgium
Kathy Kennedy, USA
Jos Kleinen, The Netherlands
Cor de Kroon, The Netherlands
Ali Kubba, UK
Regina Kulier, Austria
Miriam Labbok, USA
Patricia Lohr, USA
Tapani Luukkainen, Finland
Nandita Maitra, India
Alex Macario, USA
Evan Maijo-Wilson, USA
Mike Mbizvo, Zimbabwe
Susan McIntyre, USA
Olav Meirik, Norway
Suneeta Mittal, India
John Newton, UK
Mark Nichols, USA
Kerstin Nilsson, Sweden
Paul O'Brien, Ireland
David Paintin, UK
Bert Peterson, USA
Kresten Rubeck Petersen, Denmark
Amy Pollack, USA
Marius Rademaker, New Zealand
Ann Robbins, USA
Cecilia Pyper, UK
Jasper Radder, Netherlands
Tina Raine, USA
Michael Rosenberg, USA
Patrick Rowe, UK
Sam Rowlands, UK
Lale Say, Turkey
James Shelton, USA
Erik Schaff, USA
Ken Schulz, UK
James Scott, USA
James Shelton, USA
Nick Simpson, UK
Phillip Stubblefield, USA
Allan Templeton, UK
James Trussell, USA
Jan Vandenbroucke, Belgium
Jos Van Roosmalen,The Netherlands
Robin Van der Weiden, The Netherlands
Carla Van der Wijden, The Netherlands
Christopher Viscomi, USA
Jantien Visser, The Netherlands
Kirsten Vogelsong, USA
Helena Von Herzen, Finland
Philip Wiffen, UK
Beverly Winikoff, USA
Frederick Wu, UK
Special advisers:
Ward Cates jr., USA
Marc Keirse, Belgium
Frits Rosendaal, The Netherlands
Felicia Stewart, USA
James Trussell, USA
Jan Vandenbroucke, Belgium
Ann Webb, UK
Dutch
Cochrane Centre
-
Acknowledgements
David Paintin who was a peer reviewer for our group has
retired because of his respectable age.
Marjan
Loep passed away February 5, 2005. Marjan Loep used to work
for the Dutch Cochrane Centre in Amsterdam and was a great
support to all of us in the office in Leiden.
Cochrane Health Promotion and Public Health Field have
awarded a bursary of Aust.$ 3000 to our reviewer Janet
Hiller from the University of Adelaide to update her review:
Education for contraceptive use by women after childbirth.
Roger
Melet helped us to get the Fertility Regulation Group off
the ground and contributed greatly to the technical
development of the group till August 1998 as our first group
co-ordinator. Marjan Loep from the Dutch Cochrane Centre has
assisted in coordinating work. Clarine van Oel boosted the
methodoligical developments of the group during the time she
was working as review group coordinator.
Editorial board members Olav Meirik, Alisson Bigrigg, Tina
Mackie, Alba DiCenso and Michel Boulvain discontinued their
work. Their activities for the Fertility Regulation Group
are greatly acknowledged.
To our
great regret we announce that our Honourable Boardmember
Charlotte Ellertson passed away March 2004.
SOURCES OF SUPPORT
External
World Health Organization (WHO), Geneva, Switzerland
Ministry of Foreign / Developing Affairs, The Hague, The
Netherlands
-
Consumer
involvement
Role of consumers is to
Ensure that work undertaken by the Cochrane groups have a
consumer perspective which brings knowledge and recognition
of consumer issues and concerns to the Cochrane process in
order that information, research and service delivery result
in improved outcomes for women and men.
Ensure that consumer perspectives in the Cochrane reviews
are known about and influence future practice through
effective and known about dissemination processes.
Ensure that the consumer perspective input into the Cochrane
process is informed, is systematic and builds on the work
developed and promoted by the Cochrane Consumer Network.
None
at the moment
-
Conflict
of interest
General information and
guidelines are described in section 2.1 of the Cochrane Manual
and section 2.2 of the Cochrane Reviewers' Handbook (in this
Library). The Fertility Regulation Group is an independent group.
None of the sponsors have a direct or indirect influence of the
editorial activities.
The
conflict of interest of the editorial board: F.M. Helmerhorst
has supervised studies sponsored or assigned by various
pharmaceutical companies that manufacture oral contraceptives.
M.Gulmezoglu is working in an international research institution
(WHO), which contributes to the development and evaluation of
fertility regulation methods. D. Grimes has consulted with or
served on a speakers bureau for Berlex Laboratories, Schmid,
ALZA, Ortho-McNeil, GynoPharma, G.D.Searle and Organon, all of
which have marketed or plan to market IUDs. He served as a
court-appointed expert to the Claimant's Committee in the A.H.
Robins (distributor of the Dalkon Shield) bankruptcy proceedings.
The
collaborative work up of reviewers, referees and members of the
editorial board and the 'comments and criticism' section of
reviews may prevent conflict of interest. Any forwarded conflict
of interest will be circulated among all members of the
editorial board. Decision of the Board will be taken by majority.
If no majority will be reached, the Dutch Cochrane Centre will
be requested for assistance.
Background
Exploratory meeting held on 21/22 June 1996
Registration with the Collaboration on 13 June, 1997 as the
Cochrane Fertility Regulation Review Group.
Name changed from Cochrane Fertility Regulation Review Group
into Cochrane Fertility Regulation Group in the autumn of 1998.
First Editorial Board Meeting was held in Amsterdam on October
8, 1997
The Editorial Board has meetings twice a year.
The
editorial process refers to the refereeing of titles, protocols
and reviews written in the Cochrane Collaboration format, before
they are entered into the Cochrane Database of Systematic
Reviews (CDSR).
It has been established to produce high quality reviews which
are meaningful to both health care decision makers and the
consumers. The process is designed to be positive, open and
interactive with the aim of modifying and revising protocols/reviews
until they are of a suitable quality for publication Those
involved in the editorial process are members of the editorial
team and external peer reviewers. External peer reviewers are
either members of the Review Group not involved in the review or
people from outside the Review Group. They either have topical
or methodological expertise relevant to the review. The
editorial process differs slightly for each stage of the review
(i.e.title. protocol and review) and they are detailed
separately below. The Fertility Regulation Group (FRG) decided
to bring together the best scientific evidence available by
drawing data from randomized controlled trials (RCT) where
possible, but other types of evidence derived from observational
studies would be taken into consideration. In the period (until
February 2000), that our Group is waiting for quality control
guidelines of observational studies proclaimed by the Cochrane
Collaboration, reviews based on RCT's are preferable.
-
The Cochrane Group on Fertility Regulation addresses the
process by which people regulate their fertility, family
size and spacing of births.
The Group reviews:
-
the effectiveness and safety of fertility regulating
methods (including breast feeding, drugs, devices and
termination of unwanted pregnancy) and procedures
-
the delivery of services (effectiveness, accessibility
and acceptability)
-
how people obtain and use information
-
how people make and implement choices about fertility
regulation and preserve their reproductive health
-
issues relating to collaborative decision making and
policy development processes.
Possible areas of overlap with other CRG's are discussed and
problems are being solved by mutual agreement.
TOPICS
Contraception related reviews:
General (not specific to one method)
Methods:
any method vs any other method
Management issues related to contraceptive use :
information, counselling
timing (interval/antenatal/postnatal/postabortion)
materials used (direct counselling, information)
prescription policies (over-the -counter, healthworkers)
preprescription screening (e.g. hypertension, cervical
cancer, clotting defects etc)
Combined contraceptive methods
Methods
type of estrogen
dose of estrogen
type of progestogens
dose of progestogens
mono- vs, biphasics vs, triphasics vs sequential
route of delivery (oral, transdermal, vaginal, per injection,
etc)
regimen (eg 21/7, 22/6, etc pills per month; 84/7 pills)
Management
Information, counselling
prescription policies (over-the -counter, healthworkers)
preprescription screening (e.g. hypertension, cervical
cancer, clotting defects etc)
management of side effects
Progestogen only contraceptive methods
Methods
long acting: implantables
injectable progestogens (different types of progestogens)
progestogen only pills, ring
Management
information, counselling
prescription policies (over-the -counter, healthworkers)
preprescription screening (e.g. hypertension, cervical
cancer, clotting defects etc)
management of side effects
Intrauterine devices
Methods
inert
copper
hormonal impregnated
framed/frameless
Management
information, counselling
timing of insertion
antibiotics use for IUD insertion
screening for STIs before IUD insertion
management of side effects
Barrier methods
Methods
types
condoms (male/female), spermicides, diaphragm, cervical caps
Management
information, counselling
side effects
Natural methods
Methods
types
Management
information, counselling
side effects
Female sterilisation
Methods
abdominal /vaginal entry methods
techniques
anaesthetic methods
Management
information, counselling, consent
side effects; postoperative pain relief
Male contraceptive methods
Methods
hormonal
immunological
sterilisation
Management
information, counselling
side effects
Emergency contraception
Methods
estrogen/progestogen
progestogen only
estrogen only
antiprogestogen
IUD
Management
prescription policies (over-the-counter, medical
prescription, school nurses)
counselling, information (leaflets, peers etc)
management of side effects
Contraception in people with specific characteristics or
history of (WHO Eligibility Criteria (2000) :
diabetes or other endocrinological disorders
hypertension
thromboembolic disease
gynaecological cancer
nulliparity
sexworkers
smokers
perimenopausal
adolescents
previous history of STI
Abortion related reviews:
First trimester induced abortion
General
Methods
any method vs any other method
Management issues related to abortion
counselling and information
on abortion methods
on contraceptive methods
surveillance and care after the procedure (e.g. bath)
antibiotic use
oxytocics use
ultrasound (routine/dates), (before/after)
contraceptive use (immediate vs delayed/type)
routine counselling by eg. psychiatrists
Medical vs medical methods for abortion
Methods
type, dose, route of administration of medication used
Management
information, counselling
analgesia used (during/after)
contraceptive use after (timing, type)
hospital vs home administration
side effects
Medical vs surgical
Methods
type, dose, route of administration of medical methods
type of surgical method (aspiration, D&C)
Management
anaesthesia used
analgesia used (during/after)
side effects
Surgical vs surgical
Methods
vacuum aspiration
D&C
combined
manual vacuum aspiration
ultrasound guided evacuation
Management
information, counselling
anaesthesia used
analgesia used (during/after)
office/vs hospital
antibiotic use (route/dose/type,/duration of antibiotic)
cervical ripening (type/route of administration/dose/timing)
oxytocics use (during/after)
side effects
Second
trimester induced abortion
General
Methods
any method vs any other method
Management issues related to abortion
counselling and information
on abortion methods
on contraceptive methods
surveillance and care after the procedure (e.g. bath
routine antibiotic use
contraceptive use (immediate vs delayed/type)
routine counselling by eg psychiatrists
side effects
Medical vs medical methods for abortion
Methods
type, dose, route of administration of medication used
Management
information, counselling
analgesia used (during/after)
contraceptive use after (timing, type)
hospital vs home administration
ultrasound (routine/dates), (before/after)
side effects
Medical vs surgical
Methods
type, dose, route of administration of medical methods
type of surgical method (aspiration ( ?), D&C)
Management
information, counselling
anaesthesia used
analgesia used (during/after)
side effects
Surgical vs surgical
Methods
vacuum aspiration
D&C
combined
manual vacuum aspiration
ultrasound guided evacuation
Management
information, counselling
anaesthesia used
analgesia used (during/after)
office vs hospital
routine antibiotics
route, dose, type, duration of antibiotic
cervical ripening (type/route of administration/dose)
side effects
Abortion, Incomplete
Abortion in which not all the products of conception have
been expelled.
Abortion, Induced
Abortion brought on intentionally.
Abortion, Legal
Termination of pregnancy under conditions allowed under
local laws. (Popline Thesaurus,1991)
Adnexa
Uteri
Appendages of the uterus: the fallopian tubes, ovaries and
supporting ligaments of the uterus.
Aetiology/Etiology
Looking at the cause and nature of a disease or illness.
Amenorrhea
Abscence of menses for three months or more.
Anovulation
Suspension or cessation of ovulation.
Antibiotics
Chemical substances produced by micro-organisms, that have
the capacity, in dilute solutions, to inhibit the growth of
or to kill other organisms. Antibiotics that are
sufficiently nontoxic to the host are used as
chemotherapeutic agents in the treatment of infectious
diseases of man, animals and plants. (Dorland, 28th ed)
Antibiotic Prophylaxis
Use of antibiotics before, during or after a diagnostic,
therapeutic or surgical procedure to prevent infectious
complications.
Ampulla
Middle portion of a woman's fallopian tube and in men the
upper end of the vas deferens tube where sperm is stored.
Barrier methods
Condoms and diaphragms/pessaries.
Body
Mass Index
One of the anthropometric measures of body mass; the highest
correlation with skinfold thickness or body density.
Cervix
Bottom part of the uterus situated at the top of the vagina
which opens up to allow the birth of a baby.
Coitus
Sexual intercourse.
Culdoscopy
Endoscopic examination, therapy or surgery of the female
pelvic viscera by means of an endoscope introduced into the
pelvic cavity through the posterior vaginal fornix.
Desogestrel
Third generation progestin belonging to the distinct class
of gonane progestins like norgestrel, levenorgestrel,
gestodene and norgestimate.
Diaphragm
see Pessaries.
Dilatation and Curettage
Dilatation of the cervix uteri followed by a scraping of the
endometrium with a curette.
Ectopic Pregnancy
Development of the fertilized ovum outside the uterine
cavity. (Dorland, 27th ed)
Emergency Contraception
Contraceptive methods to be used after coitus.
Endoscopy
Endoscopic examination, therapy or surgery performed on
interior parts of the body.
Ethynodiol Diacetate
First generation progestin that belongs to the distinct
class of astranes that convert to the biologically active
component norethindrone. Other progestins of this type
include norethindrone, norethindrone acetate and
lynestrenol.
Ethinyl Estradiol
Semisynthetic estrogen with high oral estrogenic potency.
Often used as the estrogenic component in oral
contraceptives.
Expulsion IUD
Spontaneous loss of IUD from the uterus.
Fallopian Tubes
Two long muscular tubes that transport ova from the ovaries
to the uterus. They extend from the horn of the uterus to
the ovaries and consist of an ampulla, an infundibulum, an
isthmus, two ostia and a pars uterina. The walls of the
tubes are composed of three layers: mucosal, muscular and
serosal.
Family
Planning
Programs or services designed to assist the family in
controlling reproduction by either improving or diminishing
fertility.
Female Condoms
Soft loose fitting poly-urethane sheath, closed at one end
with flexible rings at both ends. The device is inserted
into the vagina by
compresing the inner ring and pushing it in. Properly
positioned, the ring at the closed end covers the cervix and
the sheath lines the walls of the vagina. The outer ring
remains outside the vagina, covering the labia.(Med Lett
Drugs Ther 1993 Dec 24;35(12):123)
Follicle Stimulating Hormone
Hormone (glycoprotein) produced and released from the
pituitary gland. In women it stimulates division of
granulosa cells inside the follicle, which produces
oestrodiol. In men it stimulates the quality (motility) of
sperm.
FSH
Follicle Stimulating Hormone.
Gestodene
A third generation progestin belonging to the distinct class
of gonane progestins like norgestrel, levenorgestrel,
desogestrel and norgestimate.
Hemorrhage
A significant loss of blood that if severe enough may
require a blood transfusion.
Iatrogenic
A complication, problem or adverse reaction as a result of
medical treatment.
Intrauterine Device
Contraceptive device placed high in the uterine fundus with
a string extending from the device through the cervical as
into the vagina. (UMDNS, 1999)
Intrauterine Device, Copper
IUD with metallic copper.
Intrauterine Device, Medicated
IUD that releases contraceptive agents.
Intrauterine System
Medicated or hormone-releasing intrauterine device.
IUD
Intrauterine Device.
IUS
Intrauterine System.
Injectable Contraception
Long-acting injectable progestational contraceptive.
Originally, depot medroxyprogesterone acetate. (DMPA)
Lactational Amenorrhea Method
Method of family planning that provides more than 98%
protection from pregnancy in the first 6 months if a mother
fully or nearly fully breastfeeds and remains amenorrheic.
LAM
Lactational Amenorrhea Method.
Laparotomy
Surgical incision made into the wall of the abdomen.
Laparoscope
Tube with a light attached to it which is inserted through a
small incision in the abdomen so the outside surface of the
uterus and other parts of a woman's reproductive system can
be examined.
Levonorgestrel
A second generation progestin that belongs to the distinct
class of gonane progestins like norgestrel, desogestrel,
gestodene, and norgestimate.
LH
Luteinizing Hormone
A glycoprotein hormone secreted by the pituitary gland. In
women it is responsible for inducing the ovulation process
inside the follicle and thus producing progesterone. In men
it stimulates the production of testosterone and is involved
with the production of sperm cells.
Lynestrenol
A first generation progestin that belongs to the distinct
class of estranes that convert to the biologically active
component norethindrone. Other progestins of this type
include norethindrone, norethindrone acetate, and ethynodiol
diacetate.
Menarche
The start of menstrual periods in adolescence.
Menopause
Permanent cessation of menstruation.
Mestranol
The methyl ether of ethinyl estradiol. Mestranol must be
converted to the active estrogen, ethinyl estradiol. Data
indicate that 30% is lost in the conversion, making 50
microgram mestranol pills bioequivalent to 35 microgram
ethinyl estradiol. (Wallach and Grimes, Modern Oral
Contraception, 2000)
Midwifery
The practice of assisting women in childbirth.
Mifepristone
Progesterone and glucocorticoid antagonist with potential
applications in terminating pregnancy, controlling
menstruation and ovulation.
Myometrium
The smooth muscle coat of the uterus, which forms the main
mass of the organ.
Norethindrone
A distinct class of synthetic first generation progestins.
Progestins of this type include norethindrone, norethindrone
acetate, lynestrenol, and ethynodiol diacetate. These
progestins are estranes and convert to the biologically
active component norethindrone.
Norgestrel
A second generation progestin that belongs to the distinct
class of gonane progestins like levenorgestrel, desogestrel,
gestodene, and norgestimate. Norgestrel is less potent than
levenorgestrel.
Norplant
Subdermal implant system releasing levenorgestrel.
Oligomenorrhea
Abnormally irregular, less frequent menstruation, associated
with anovulation.
Oral
Contraceptives
Compounds, usually hormonal, taken orally in order to
prevent ovulation and thus the occurrence of pregnancy. The
hormones are primarily a progestogen, generally combined
with an estrogen.
Oral
Contraceptives, Combined
Fixed combination of progestogens and estrogens.
Oral
Contraceptives, Sequential
Drugs administered orally and sequentially for contraceptive
purposes.
Oral
Contraceptives, Low-dose
Products containing less than 50 microgram ethinyl estradiol.
Oral
Contraceptives, First Generation
Products containing generally progestogens as lynesterenol
or norethisteron, mostly combined with 50 microgram or more
of ethinyl estradiol.
Oral
Contraceptives, Second Generation
Products containing progestogens as levenorgestrel,
norgestimate, and other members of the norethindrone family,
mostly combined with 30 or 35 microgram ethinyl estradiol.
Oral
Contraceptives, Third Generation
Products containing progestogens as desogestrel or gestodene
mostly combined with 30 microgram or less ethinyl estradiol.
Pearl
Index
Number of failures per 100 women-years of exposure. The
denominator is the total months or cycles of exposure from
the onset of a method until completion of the study, an
unintended pregnancy, or discontinuation of the method. The
quotient is multiplied by 1200 if the denominator consists
of months or by 1300 if the denominator consists of cycles.
Pelvic
Inflammatory Disease
Infection of the uterus and fallopian tubes.
Pessary
Instrument placed in the vagina to support the uterus or
rectum or to serve as a contraceptive device. (Dorland, 28th
ed)
PID
Pelvic inflammatory disease or salpingitis.
Placebos
Pills, injections or treatments missing the active component
of interest, administered to experimental control groups to
correct for nonspecific effects.
Pregnancy in Adolescence
Pregnancy in women under 19.
Pregnancy Rate
Ratio of the number of conceptions that occur during a
period to the mean number of women of reproductive age.
(POPLINE Thesaurus, 1991)
Progestasert
See progesterone-IUD
Progesterone-IUD
Membrane enclosed reservoir inserted in uterus containing
progesterone; once-a-year contraceptive.
Salpingitis
Inflammation of the fallopian tubes.
Sepsis
Infection that has spread throughout the body.
Serum
screening
The systematic testing of blood to check for exposure to
disease or the presence of a disorder that can be detected
in the blood.
Spermatocides / Spermicides
Chemical substances that are destructive to spermatozoa used
as topically administered vaginal contraceptives.
Sponge
The vaginal contraceptive sponge is a sustained-release
system for a spermicide. The sponge also absorbs semen and
blocks the entrance to the cervical canal.
STD
Sexually Transmitted Diseases.
Subdermal implants
Long-acting, low-dose, reversible progestin-only method of
contraception for women, consisting of implantable,
subdermal capsules.
Synthetic Progestational Hormones
Compounds obtained by chemical synthesis that possess
progestational activity, but differ in structure from
naturally occurring progestational hormones.
Tubal
Patency
The fallopian tubes are intact and unblocked, thus capable
of transporting an ovum from the fimbriae to the ampulla,
sperm from the uterus to the ampulla and a fertilised ovum
to the uterus.
Tubal
Sterilization
Surgical interruption of the fallopian tube.
Uterine Cavity
The pelvic space where the uterus is situated.
Uterine Perforation
Penetration through the uterine wall caused by trauma,
surgery or a weak spot.
Vas
Deferens
A thick-walled tube going from a man's testis into the
ejaculatory duct. This tube carries the sperm from the
epididymis (where sperm is stored and nurtured), to the
penis.
Vasectomy
Surgical removal of the ductus deferens, or a portion of it.
It is done in association with prostatectomy, or to induce
infertility. (Dorland, 28th ed)
Inclusion criteria
A trial should be included in the Register if, on the basis
of the best available information, it is judged that the
individuals ( or other units) followed in the trial were
definitely or possibly assigned prospectively to one of two
(or more) alternative forms of health care using, random
allocation or some quasi-random method of allocation (such
as alternation, date of birth, or case record number).
In addition:
If one or more outcomes were assessed using "double blinding"
or "double masking" such that neither the participant/patient
nor the assessor was aware of the intervention received, but
randomization is not mentioned explicitly in the text, a
trial should be included.
Crossover trials, in which patients have been assigned to
the first intervention using random or quasi-random
allocation, should be included.
Reports of trials dealing only with animals should not be
included.
Units of randomization may be individuals, groups (such as
communities or hospitals), organs or other parts of the
body.
A report of a randomized trial should be included even when
no results are presented or when results are limited to the
analyses of baseline variables.
Each
trial report is downloaded from CENTRAL/Cochrane Controlled
Trials Register and is checked initially to assess whether
it falls into the scope of the Fertility Regulation Group.
The title and abstract of the trial report is retrieved and
assessed to ascertain whether it is identifiable as a
randomized or quasi-randomized controlled trial according to
the criteria described above. If it is, then it is included
in the Specialized Register. If the abstract is unclear or
unavailable, then the full report is obtained and assessed
for possible inclusion.
Search
strategies for the identification of studies
Electronic searches
CENTRAL/Cochrane Controlled Trials Register
CENTRAL is the Cochrane Collaboration's internal register of
studies, which may be relevant for inclusion in Cochrane
reviews. Its development is guided by the Trials Registers
Development Group and the first full version was made
available in issue 4 of The Cochrane Library in October
1997. CENTRAL aims to include all relevant reports that have
been identified through the work of the Cochrane
Collaboration. It can be searched by anyone within the
Collaboration needing to identify studies for a Cochrane
review. It is the source from which the Collaboration will
supply public domain databases of trial information such as
The Cochrane Controlled Trials Register and MEDLINE.
Responsibility for the development of CENTRAL/CCTR rests
with an Advisory Group, responsible to the Cochrane
Collaboration Steering Group, which is convened by Kay
Dickersin.
MEDLINE (1966 - )
The
MEDLINE database is produced by the US National Library of
Medicine. The MEDLINE database is widely recognized as the
premier source for bibliographic and abstract coverage of
biomedical literature. MEDLINE encompasses information from
Index Medicus, Index to Dental Literature, and International
Nursing, as well as other sources of coverage in the areas
of allied health, biological and physical sciences,
humanities and information science as they relate to
medicine and health care, communication disorders,
population biology, and reproductive biology. More than
3,600 journals are indexed, plus selected monographs of
congresses and symposia (1976-1981). Abstracts are included
for about 67% of the records.
There
are several versions of MEDLINE - with different software
for searches - all based on the same database. Two different
search strategies are listed below: one using OVID (paid
access ), the other using PubMed (free access). The search
strategy for identifying possible randomized controlled
trials was initially devised for OVID by Carol Lefebvre and
Steve McDonald (UK Cochrane Centre) and is extended with the
search for 'volunteers' in abstract and title. The OVID
search strategy is still preferred to the search strategy
for PubMed. The PubMed search strategy is described in:
Nixon S, O'Brien K, Glazier RH, Wilkins AL. Aerobic exercise
interventions for people with HIV/AIDS (Cochrane Review).
In: The Cochrane Library, Issue 2, 2001. Oxford: Update
Software), and was adapted from Robinson (Robinson KA,
Hinegardner PG, Lansing P. Development of an optimal search
strategy for the retrieval of controlled trials using
PubMed. Poster presented at: 6th International Cochrane
Colloquium, Oct 22-26, 1998, Baltimore, MD. with minor
additions from Fraser (Fraser C, Thomson-O'Brien MA.
Identifying non-randomized studies in MEDLINE. Poster
presented at: 6th International Cochrane Colloquium, Oct
22-26, 1998, Baltimore, MD.)
Search
strategy for MEDLINE: generic part for randomized controlled
and controlled clinical trials
MEDLINE (OVID; paid access)
1.randomized controlled trial.pt.
2.controlled clinical trial.pt
3.randomized controlled trials.sh
4.random allocation.sh
5.double-blind method.sh
6.single-blind method.sh
7.clinical trial.pt
8.exp clinical trials/
9.(clin$ adj25 trial$).ti,ab
10.((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or
mask$)).ti,ab
11.placebos.sh
12.placebo$.ti,ab
13.random$.ti,ab
14.research design.sh
15.volunteer$.ti,ab
16.latin square.tw
17.cross-over studies.sh
18.crossover.tw
19.cross-over.tw
20.animal.sh
21.human.sh
22.20 not 21
23.or/1-19
24.23 not 22
PubMed
(free: http://www.ncbi.nlm.gov/PubMed/)
((((((((((((((((((((((((
"randomized controlled trials"[MESH:noexp] OR
"random allocation"[MESH:noexp]) OR
"double-blind method"[MESH:noexp]) OR
"single-blind method"[MESH:noexp]) OR
"clinical trials"[MESH]) OR
"placebos"[MESH:noexp]) OR
"research design"[MESH:noexp]) OR
"comparative study"[MESH:noexpl]) OR
"evaluation studies"[MESH]) OR
"follow-up studies"[MESH:noexpl]) OR
"prospective studies"[MESH:noexpl]) OR
"cross-over studies"[MESH:noexpl]) OR
"intervention studies"[MESH:noexpl]) OR
"randomized controlled trial"[pt]) OR
"controlled clinical trial"[pt]) OR
"clinical trial"[pt]) OR
"clinic* trial*" [title/abstract word]) OR
(((("singl*"[title/abstract word] OR "doubl*"[title/abstract
word]) OR
"tripl*"[title/abstract word]) OR "trebl*"[title/abstract
word]) AND ("blind*"[title/abstract word] OR
"mask*"[title/abstract word])) OR
"placebo*" [title/abstract word]) OR
"random*"[title/abstract word]) OR
"latin square"[title/abstract word]) OR
"control*"[title/abstract word]) OR
"prospectiv*"[title/abstract word]) OR
"volunteer*"[title/abstract word]) NOT
("animal"[MESH] NOT "human"[MESH]))
EMBASE
(1980 - )
In addition to Central/CCTR and MEDLINE, EMBASE (the
Excerpta Medica database produced by Elsevier Science)
should be searched. EMBASE is a major biomedical and
pharmaceutical database indexing over 3,500 international
journals in the following fields: drug research,
pharmacology, pharmaceutics, toxicology, clinical and
experimental human medicine, health policy and management,
public health, occupational health, environmental health,
drug dependence and abuse, psychiatry, forensic medicine,
and biomedical engineering/instrumentation.
Search
strategy for EMBASE: Generic part for randomized controlled
and controlled clinical trials
EMBASE (Ovid)
1.clinical article/
2.clinical study/
3.clinical trial/
4.controlled study/
5.randomized controlled trial/
6.major clinical study/
7.double blind procedure/
8.multicenter study/
9.single blind procedure/
10.phase 3 clinical study/
11.phase 4 clinical study/
12.crossover procedure/
13.placebo/
14.or/1-13
15.allocat$.ti,ab
16.assign$.ti,ab
17.blind$.ti,ab
18.((clinic$ adj25 (study or trial)).ti,ab
19.compar$.ti,ab
20.control$.ti,ab
21.cross?over.ti,ab
22.factorial$.ti,ab
23.follow?up.ti,ab
24.placebo$.ti,ab
25.prospectiv$.ti,ab
26.random$.ti,ab
27.((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or
mask$).ti,ab
28.trial.ti,ab
29.(versus or vs).ti,ab
30.or/15-29
31.14 or 30
32.human/
33.nonhuman/
34.animal/
35.animal experiment/
36.33 or 34 or 35
37.32 not 3
38.31 not 36
39.31 and 37
40.38 and 39
Additional Electronic Databases
CINAHL
(1982 - )
The Cumulative Index to Nursing & Allied Health (CINAHL)
database provides authoritative coverage of the literature
related to nursing and allied health. Virtually all
English-language publications are indexed along with the
publications of the American Nurses Association and the
National League for Nursing.
HealthStar (1975 - )
HealthSTAR contains citations to the published literature on
health services, technology, administration, and research.
It focuses on both the clinical and non-clinical aspects of
health care delivery.
PsycINFO (1887 - )
The PsycINFO and PsycLIT databases cover the professional
and academic literature in psychology and related
disciplines including medicine, psychiatry, nursing,
sociology, education, pharmacology, physiology, linguistics,
and other areas. Coverage is worldwide, and includes
references and abstracts to over 1300 journals (and in
PsycINFO, to dissertations) in more than 30 languages, and
to book chapters and books in the English language. Over
50,000 references are added annually. Popular literature is
excluded.
POPLINE (1970 - ), free access: http://igm.nlm.nih.gov/
POPulation information onLINE provides worldwide coverage of
population, family planning, and related health issues,
including family planning technology and programs, fertility,
and population law and policy. In addition, POPLINE focuses
on particular developing-country issues including demography,
AIDS and other sexually transmitted diseases, maternal and
child health, primary health care communication, and
population and environment. POPLINE citations are searchable
with POPLINE keywords as well as MESH headings. The file is
produced by the Population Information Program at the Johns
Hopkins School of Public Health. The database is funded
primarily by the United States Agency of International
Development.
Search
strategies for the identification of studies
Electronic
searches
The following search strategy
has been designed to search CENTRAL/Cochrane Controlled
Trials Register published in The Cochrane Library to
identify reports of randomized or quasi-randomized
controlled trials within the scope of fertility regulation.
This search will be run for the first time in The Cochrane
Library, Issue 2, 2001 and thereafter for each release of
The Cochrane Library. All languages will be included for
consideration. The terms in upper case denote 'controlled
vocabulary' or 'Thesaurus' terms, e.g. MeSH (Medical Subject
Headings) applied by indexers of electronic databases such
as MEDLINE and EMBASE to describe the subject content of
each record. The terms in lower case denote 'free text' or 'textwords'
which are used by the author to describe the subject content
of the study. Drug classes and individual names for
contraceptives, including their proprietary names used in
different countries where known, will be included. This
strategy will be regularly
revised to include the annual
revision of MeSH terms to allow for new terms to be added
and existing terms to be changed as appropriate. Until the
New Generation Cochrane Library version is available, the
MeSH terms which have been added to MEDLINE since 1998 will
be included as free text phrases.
#1explode CONTRACEPTION
#2CONTRACEPTION-BEHAVIOR
#3contracept*
#4explode FAMILY-PLANNING
#5family planning or planned parenthood or birth control
#6birth regulat* or population regulat* or fertility regulat*
or birth spacing
#7population control or fertility control or reproduct*
control
#8pregnan* near (prevent* or interrupt* or terminat*)
#9POPULATION-CONTROL
#10FAMILY-PLANNING-POLICY
#11explode CONTRACEPTIVE-DEVICES
#12intrauterine device* or intra-uterine device* or IUD* or
TCu380a or CuT-200 or Gynefix
#13barrier method* or condom* or vaginal sponge* or cervical
cap*
#14explode REPRODUCTIVE-CONTROL-AGENTS
#15algestone acetophenide or neolutin depositum or
chlormadinone acetate or luteran or gestafortin or prostal
or cyproterone acetate or andro-diane or androcur or cyprone
or cyprostat or demegestone or lutionex or desogestrel or
marvelon or mercilon or dienogest or drospirenone or
ethinyloestradiol or ethinylestradiol or progynon-c or
estigyn or primogyn-c or estinyl or turisteron or lynoral or
etifollin or ethynodiol diacetate or lutometrodiol or
luteonorm or femulen or etonogestrel or gestodene or
femodene or minulet or lynoestrenol or orgametril or exluton
or exlutona or exlutena or medroxyprogesterone acetate or
depo-provera or depocon or farlutal or prodafem or provera
or depo-ralovera or ralovera or depo-prodasone or gestoral
or prodasone or clinofem or clinovir or depo-clinovir or
g-farlutal or lutoral or perlutex or petogen or
depo-progevera or progevera or cykrina or gestapuran or
prodafem or amen or curretab or cycrin or mestranol or
ortho-novum or norinyl-1 or mifepristone or mifegyne or
nomegestrol acetate or lutenyl or norethisterone or
norethisterone acetate or norethisterone enanthate or
micronovum or primolut-nor or locilan or micronor or noriday
or primolut-n or norlutate or milligynon or norfor or
noristerat or norluten or gestakadin or sovel or conludag or
nur-isterate or mini-pe or menzol or sh-420 or utovlan or
aygestin or nor-qd or norgestimate or norgestrel or
levonorgestrel or dexnorgestrel or microlut or microval or
mirena or norplant or mikro-30 or 28-mini or levonova or
microluton or follistrel or neogest or norgeston or
postinor-2 or ovrette norgestrienone or ogyline or
ormeloxifene or centchroman or progesterone or gestagen or
proluton or progestogel or utrogestan or gesterol or
prometrium or progestasert or progestosol or utrogestan or
esolut or proluton or prontogest or progestan or cyclogest
or cutifitol or progeffik or crinone or testosterone
enanthate
#16ovulat* near (supress* or inhibit* or prevent*)
#17ABORTION-APPLICANTS
#18explode ABORTION-INDUCED
#19abortion or abortifacient*or termination or morning after
pill or RU-486 or Yuzpe
#20explode STERILIZATION-SEXUAL
#21(female or woman or women or male or man or men) near
sterili*
#22vasectom*
#23SEXUAL-ABSTINENCE
#24periodic* abstinen* or sexual* abstinen* or coitus
interruptus
The
above subject search strategy will be adapted to search
MEDLINE, EMBASE, HealthStar, PsycINFO, CINAHL and POPLINE in
the first instance and full details will be published in
future issues of the Fertility Regulation Group's Module.
Hand
searching
The
following journals are being searched prospectively by hand:
Advances in Contraception (1985-1997 completed by Dutch
Cochrane Centre; 1998- search ongoing)
The Journal of Family Planning and Reproductive Health Care
[formerly Journal of Family Planning Doctors and British
Journal of Family Planning] (1975-1997 completed; 1998-
search ongoing)
Contraception (1970-1996 completed by Cochrane Menstrual
Disorders Group;1997- search ongoing)
European Journal of Contraception and Reproductive Health
Care (1996- search ongoing)
The
following journals are newly registered for searching
prospectively by hand:
Family Planning Perspectives (1969-)
Studies in Family Planning (1963-)
Population Reports:
Series A Oral Contraceptives (1974-)
Series B Intrauterine Devices (1973-)
Series C Female Sterilization (1973-)
Series D Male Sterilization (1973-)
Series F Pregnancy Termination (1973-)
Series G Prostaglandins (1973-)
Series H Barrier Methods (1973-)
Series I Periodic Abstinence (1973-)
Series J Family Planning Programs (1973-)
Series K Injectables and Implants (1975-)
Series M Special Topic Monographs (1977-)
Other
strategies
To identify additional high yield journals to be searched by
hand the following strategies will be carried out:
Search Ulrich's International Directory of Periodicals by
subject to generate a list of potential journals within the
scope of fertility regulation; search MEDLINE and EMBASE for
randomised controlled trials in these journals and rank them
according to yield to identify priority journals for
immediate searching.
Generate a list of journals containing the trial reports in
the Group's Specialized Register. Check the Master List of
journals being searched by hand to see if any are not
already being searched.
Search POPLINE for randomised controlled trials and rank
results by journal title. Check the Master List to see if
any are not already being handsearched.
To
identify conference proceedings to be searched by hand the
following strategies will be carried out:
Generate a list of relevant conferences by asking experts in
the field at which conferences they present their research
and identify the sources in which the meeting/conference
abstracts are published.
Search the British Library Inside (online database includes
information on over 100,000 conference proceedings worldwide)
by subject.
Ensure that all sections of journals identified for
handsearching, especially supplements, are searched as these
are likely to contain abstracts of trials presented at
conferences.
Planned
searching activities
The
above subject search strategy (designed to search the
CENTRAL/Cochrane Controlled Trials Register, published in
The Cochrane Library) will be adapted to search MEDLINE,
EMBASE, PsycINFO, CINAHL and POPLINE in the first instance.
Full details of the search strategies for these databases
will be published in future issues of the Fertility
Regulation Group's Module.
Methods
used in reviews
Search
strategies
Access
to specialised register by reviewers
The Fertility Regulation Group's Specialized Register has
been submitted for the first time for inclusion in The
Cochrane Library, Issue 3, 2001. The Group's Specialized
Register code SR-FERTILREG can be incorporated into a
search. The Trials Search Co-ordinator is happy to help
design and run search strategies for reviewers, particularly
on electronic databases which are not accessible to them.
The search strategy designed to generate the Group's
Specialized Register will be run on each release of The
Cochrane Library and it is intended that trial reports
identified in this way, which are potentially relevant to
specific reviewers undertaking reviews registered with the
Fertility Regulation Group, will be sent to the reviewers
concerned.
Reviewers are advised to:
Search at least Central/ Cochrane Controlled Trials Register
(CCTR), MEDLINE, and EMBASE (for generic search strategies
see the section on Electronic searches below;
Search any other specialist databases in their topic area(s)
as well as the bibliographies of papers they acquire.
Descriptions of possible valuable databases are given in the
section on electronic searches;
Contact authors of all trials and/or reviews relevant to
their review topic to request information on any further
trials of which they may be aware, whether unpublished or "on-going";
Contact pharmaceutical industries to request information on/data
concerning trials conducted by them;
Visit our web site, http://www.medfac.leidenuniv.nl/cochrane/,
for search strategies, useful links, examples of letters to
authors (in the near future);
Ask for help from the Review Group Coordinator if there are
any problems.
Reviews should only include evidence provided by randomised
controlled trials and controlled clinical trials until a new
policy regarding non-randomised evidence is developed. Two
reviewers should independently assess each potentially
eligible trial for inclusion in the review. A third reviewer
should be used to resolve any discrepancies regarding
eligibility. Trial publications should be assessed for
eligibility with the results section (and any other area
where results may appear) masked. Where necessary additional
information should be sought from the principal investigator
of the trial concerned.
Assessment
of methodological quality
Assessment of methodological quality
Two independent reviewers should independently assess the
methodological quality of all eligible studies and the level
of agreement should be reported in the review. Any
disagreement will be resolved by discussion with a third
reviewer, and any differences in opinion which can not
easily resolved, will be referred to the editorial team. To
enhance the (future) quality of the systematic reviews,
reviewers are encouraged to first pilot test the assessment
of methodological quality on a set of articles available
from the Review Group Co-ordinator.
An important dimension of study quality relates to the
extent to which systematic error or bias is minimised. In
clinical trials, potential biases fall into four categories,
and should be therefore assessed for all reviews:
Selection bias: biased allocation to comparison groups
Method of avoidance: randomisation
Generation of unbiased allocation sequence:
Adequate: random numbers, drawing of lots, tossing a coin,
shuffling cards, etc.
Inadequate (possibly related to prognosis): case record
number, date-of-birth, day, week, months of admission
Concealment of allocation sequence
Adequate (cannot be foreseen): central randomisation, coding
of drugs in pharmacy, numbered, sealed envelopes, etc
Inadequate (can be foreseen): open allocation schedules,
alternation, unsealed or non-opaque envelopes, etc.
Performance bias: unequal provision of care apart from the
treatment under evaluation
Method of avoidance: blinding of care providers and patients
Adequate
Inadequate
Detection bias
Method of avoidance: blinding of outcome assessors
Adequate
Inadequate
Attrition bias: biased occurrence & handling of protocol
deviations, withdrawals and losses to follow-up
Method of avoidance: all randomised patients should be
included in the analyses, regardless of their study
adherence ('Intention to treat analysis')
Adequate
Inadequate
If the
article does not contain information to judge the presence
or absence of these biases, the reviewers are recommended to
contact the authors for additional information. If the
authors cannot be contacted or the information is no longer
available, the criteria should be scored as 'Inadequate'.
The
use of summary scores from quality scales is problematic.
Results depend on the choice of the scale, and the
interpretation of findings is difficult. It is therefore
preferable to examine the influence of individual components
of methodological quality. This is best done using
sensitivity analysis.
For
further information on the assessment of methodological
quality, please refer to Section 6, page 39 - 50, of the
Cochrane Reviewers' Handbook, version 4.1 (updated December
2000), or to chapter 5, page 87 - 108, of Systematic Reviews
in Health Care by M. Egger, G.D. Smith, and D.G. Altman (eds.),
2001, London: BMJ Publishing Group.
Crossover and cluster randomised studies should in principle
be included in the systematic review. Standard quality
criteria also apply to these trials. However, reviewers
should consider whether there was a substantial possibility
of carryover between the subsequent conditions in crossover
studies in a sensitivity analysis.
Data
collection
At
least two reviewers should independently extract the data.
Reviewers are asked to record at least the following general
data in addition to the pre-specified variables of interest
(outcomes), using a structured data extraction form. If data
is missing from a trial report the reviewer is encouraged to
contact the original investigator in order to request
additional information.
Identification:
ID Review
Article
ID database of references
First author
Year
ID Reviewer
Study
design:
Randomised controlled trial (RCT)
Controlled clinical trial (CCT)
Cross-over study
Cluster randomised study
Intervention
Treatment groups
Participants:
Inclusion criteria
Exclusion criteria
Number
Age
Parity
Social economical status
Educational level
Ethnicity
Previous contraceptive method
Health status
Smoking
Body mass index
Setting:
Country
Location of care
Methods:
Unit of allocation
Unit of analysis
Loss to follow-up
Quality
Generation of unbiased allocation sequence:
Concealment of allocation sequence
Blinding of care providers and patients
Blinding of outcome assessors
Intention to treat analysis
Statistical guidelines are available from the Group's
editorial base and further guidance can be obtained from the
statistical editor.
Statistical guidelines are provided by the Group and are as
follows:
STATISTICAL GUIDELINES FOR REVIEWERS IN THE FERTILITY
REGULATION GROUP
Introduction
With these guidelines we want to assist reviewers in making
decisions about which are the most appropriate statistical
methods to use. Reviewers undertaking or updating a Cochrane
Review will in future be asked to follow the guidelines
detailed below. If they choose to use other options, then
this must be explicitly stated in the methods section of the
review, and preferably discussed with the editor. Reviewers
should, wherever possible, seek the advice or help of a
statistician before embarking on a review. They should also
use caution when extracting and interpreting their data, and
should work closely with the editorial group and/or
statistician.
These
guidelines attempt to suggest practical strategies for an
initial review of an area. In some cases a fuller analysis
may then be required, perhaps warranting obtaining
individual patient data, or further statistical modelling
involving fairly strong assumptions. However a decision on
whether this effort is warranted can only really be taken
once the initial systematic review is complete.
For
more information on the statistical methods and definitions
of statistical terms used in Cochrane Reviews, please refer
to section eight of the Cochrane Collaboration Handbook for
reviewers (http://www.cochrane.dk/cochrane/handbook/handbook.htm).
Please
note these guidelines are for assisting people in writing
the text of the review. Users of the Cochrane Library are
able to change the defaults and look at the data in
different ways.
Included studies
Both RANDOMISED CONTROLLED TRIALS and CONTROLLED CLINICAL
TRIALS (also mentioned as quasi-randomised or
pseudo-randomised; Medline uses the term 'controlled
clinical trials') are eligible for inclusion in the
analyses. Although randomised controlled trials are superior
to controlled clinical trials, reviewers should realise that
they assess the quality of the report and that the
requirements from journals have been changed over time.
Furthermore, for an author who is familiar to the work of
the Cochrane Collaboration it might be better not to respond
to a request for information on randomisation and
concealment of allocation, if this would disqualify their
study. Reviewers should therefore investigate the influence
of this and other indicators of biases (i.e. generation of
unbiased allocation sequence, concealment of allocation
sequence, blinding of care providers and patients, blinding
of outcome assessors, intention-to-treat analysis) on their
outcome measures in sensitivity analyses, and incorporate
these findings in their discussion and conclusions.
Ref: Meta-analyses involving cross-over trials:
methodological issues. Diana R, Elbourne DR, Altman DG,
Higgins JPT, Curtin F, Worthington HV, Vail A. Int J
Epidemiol 2002 (in press).
It is
common in our group to consider discontinuation rates and/or
side effects that were reasons for discontinuation of
contraceptive method. Reviewers should be aware that this
kind of outcome measure is related to loss to follow-up, and
that studies with high loss to follow-up might be the ones
investigating methods with unfavourable user profiles.
Finally, reviewers should conduct their analyses according
to the intention-to-treat principle by using the original
number randomised to each group, and not the sample size
excluding protocol deviations or those lost to follow-up.
Outcomes with no data
It is important to state beforehand what types of outcomes
would answer the "real clinical problem" and, if necessary,
to draw attention to the fact that they have not been
measured.
Unit
of measurement problems
In our scope, outcomes may be registered at the person
level, but also at the level of menstrual cycle. It is often
very difficult to convert data provide by number of
menstrual cycles into number of women, and vice versa.
Effect
measures
Event
data (Dichotomous Data)
Simple binary variables are common in trials of fertility
regulation. In MetaView several options are available as
effect measure. Reviewers should either use the relative
risk or the odds ratio as the effect measure for dichotomous
data:
The RELATIVE RISK or RISK RATIO (RR): For a single trial, if
the outcome in each group is expressed as a rate, the
relative risk is the ratio of the rate in the experimental
group to that in the control group. RR are more easy to
interpret than odds ratio's, but it affects trial weights in
meta-analysis (independent of sample sizes) if event rates
are very variable across trials, or event rates are very
high.
The ODDS RATIO describes the odds of a patient in the
experimental group having the outcome relative to a patient
in the control group. For rare outcomes, the relative and
the odds ratio are virtually interchangeable, but for more
common outcomes they can be very different. OR are difficult
to interpret, and might be misinterpreted as RR,
consequently overestimates the benefits and harms of an
intervention. If the OR is used, special attention should be
paid to properly explaining any differences. Reviewers may
convert the OR into RR before interpretation of results, or
they may derive the relative odds reductions to use in the
presentation of results.
The PETO ODDS RATIO is an approximation of the Odds Ratio (OR),
and was initially the only effect measure in MetaView. Now
that other methods are available, Peto-OR should not be used
anymore, because the Peto-OR becomes biased when treatment
effects become larger, or when randomisation is unbalanced.
Some
outcomes take the form of a count. Examples include number
of pregnancies, number of occurrences of a particular side
effect. These should always be defined with respect to a
time period. It may be helpful to specify particular periods
of interest e.g. one week, one month, three months, one year
etc. In practice papers are likely to vary, so it may be
helpful to record the nearest available measure, in the form
AVERAGE NUMBER OF EVENTS PER GROUP, (AVERAGE) PERIOD OF
FOLLOW UP, and then calculate a RATE by dividing the first
by the second. The difference between the groups can then be
summarised, for example by a ratio of rates.
Continuous data
It is worth documenting (for each group in each trial, for
each time point of interest) the raw mean, standard
deviation and number of observations, eventually both in
women and in menstrual cycles, as well as the change,
standard deviation of the change and the number of
observations (in women as well as in menstrual cycles).
At each time point of interest, for continuous data the
WEIGHTED MEAN DIFFERENCE should be used whenever outcomes
are measured in a standard way across studies (e.g.
operation time, biochemical parameters). This has the
advantage of summarising results in natural units that are
easily understood (e.g. the mean difference in operation
time between the treatment and control group). If there is
only one study for a particular outcome, then the WEIGHTED
MEAN DIFFERENCE should be used.
Occasionally, it may be desirable or necessary to summarise
results across studies with outcomes that are conceptually
the same but measured in different ways (e.g. side effects,
outcomes measured in women and menstrual cycles). Under
these circumstances STANDARDISED MEAN DIFFERENCES can be
used. However, because this approach makes it possible to
combine the results of dissimilar studies, reviewers must be
particularly cautious in deciding whether such an analysis
makes sense in interpreting the results.
Reviewers should be aware of the possibility of skewed data
and the potential problems it presents. To detect skew in
measurements that are always positive divide the mean by the
standard deviation. If the result is less than 1.64 there is
some positive skew. Where there is positive skew, reviewers
should perform sensitivity analyses including and excluding
these trials (see section below on sensitivity analysis).
In many cases, only means and standard errors are reported.
Reviewers can convert standard errors into standard
deviations by using the formula:
Standard deviation = standard error x square root of n (where
n = group sample size)
Fixed
effect versus random effects
Both the FIXED EFFECT model and the RANDOM EFFECTS model can
be used to analyse the data. The fixed-effect models assume
that all the studies are estimating the same "true" effect,
and that the variation in effects seen between trials is
only due to chance. The random-effects model assumes that
the treatment effects from individual studies are a random
sample from a "population" of different effect sizes that
follows a normal distribution. There will be almost always
being differences in baseline risk of patients in trials
carried out in different trials and at different times.
Initially, only fixed effect models were available in
MetaView (the estimation of the Peto-OR corresponds to the
fixed effect model). Whether or not to use the fixed or
random effect model is still a matter of ongoing debate.
Reviewers should make a documented choice in their protocol
for one of these. The random effects model will tend to give
a more conservative estimate, but the results from the two
models should basically agree where there is homogeneity (between
studies).
Heterogeneity
An important component of a systematic review is the
investigation of the consistency of the treatment effect
across trials (heterogeneity). The fixed effect model does
not allow for between trial variations. In the presence of
significant heterogeneity (i.e. the test for homogeneity
results in a p value of 0.05/0.10 or less) the between trial
variation should be acknowledged and this corresponds to the
use of the random effect model. Even when stratifying
reduces heterogeneity, there still will be residual
variation between trials, and this should be included in the
model, although use of this model does not overcome the
problem of heterogeneity. A non-significant test cannot be
interpreted as evidence of homogeneity. Tests of
heterogeneity have low statistical power and may fail to
detect as statistically significant even a moderate degree
of genuine heterogeneity. All reviewers should therefore
consider possible resources of heterogeneity where possible,
through examining whether differences in study results are
related to characteristics of the studies (quality, year of
study, place of study etc.), or specific clinical or
demographic differences between studies. It is advisable to
do a sensitivity analysis, starting by excluding trials of
the poorest quality and see whether homogeneity improves. If
reviewers refrain from pooling, they still need to explore
the sources of heterogeneity as this yields information that
increase our understanding of influential conditions that
modify treatment effects.
Subgroup analysis
Wherever possible, any hypotheses about potential subgroups
(i.e. different doses of a drug, age groups) should be
stated a priori (in the protocol for the review). The number
of planned subgroup analyses should be kept to a minimum to
avoid spurious findings. Where there is significant
heterogeneity in the results and no subgroup analysis has
been stated a priori, subgroup analysis may be used, but the
results interpreted with caution. Readers should be informed
that the subgroup analysis was done because of the
significant heterogeneity found, not because of an a priori
hypothesis.
Sensitivity analysis
Once the data has been analysed, reviewers should consider
how sensitive the results are in relation to the way the
analysis was done. The following is a minimum set of
sensitivity analyses that reviewers should perform:
1. Repeat the analysis excluding unpublished studies (if
there were any).
2. Repeat the analysis excluding studies of the lowest
quality (which would have been done already if there were a
heterogeneity problem).
3. If there were one or more very large studies, repeat the
analysis excluding them to look at how much they dominate
the results.
4. Repeat the analysis excluding other types of studies,
depending on the particular review and the degree to which
there were choices about the inclusion/exclusion criteria (e.g.
with/without trials that had different dosages).
If there are a reasonable number of studies, a funnel plot
should be drawn to examine the possibility of publication
bias. A funnel plot is a graphical display of sample size
plotted against effect size. A gap on one side of the wide
part of the funnel indicates that some studies have not been
published or located.
These
guidelines were modified from the guidelines developed by
the Menstrual Disorders Group and the Cystic Fibrosis and
Genetic Disorders Group.
Useful
references
L'Abbe KA, Detsky AS, O'Rourke K. Meta-analysis in clinical
research. Annals of internal medicine 1987; 10: 224-233.
Petitti DB. Meta-Analysis, and Cost-Effectiveness Analysis.
Monographs in Epidemiology and Biostatistics 1994; 10.
Systematic Reviews in Health Care by M. Egger, G.D. Smith,
and D.G. Altman (eds.), 2001, London: BMJ Publishing Group.
Reporting of reviews
Still
in progress
Editorial
process
Titles
must be registered with the editorial base using a standard
form (available at the Editorial Office in Leiden from the
Review Group Co-ordinator Anja Helmerhorst), to prevent
possible wasted time and duplication of effort if more than
one person unknowingly embarks on the same review. The FRG
encourages reviewers to collaborate with at least one other
person, so that there is a mix of content and methodological
expertise. In Leiden at the Editorial Office a database with
collaborators and their interests is maintained. It is also
advisable to involve people from more than one centre.
Reviews must have a nominated contact reviewer who is
responsible for liaising with the editorial team and other
reviewers. All titles will be reviewed by all members of the
editorial team and considered for their potential overlap,
mixture of expertise, feasibility and suitability for a
systematic review. This process should take no longer than
two weeks.Once a title has been approved, it will appear in
the module.
If more than one person proposes to do the same review the
Review Group Co-ordinator will attempt to establish a
collaboration between the parties and will arbitrate in the
case of disagreements.
Protocols must be delivered within three months of a title
being registered. Titles which have been registered for more
than twelve months, for which protocols have not been
forthcoming, are 'de-registered' and become generally
available once more for review by other Group members.
The
Group encourages reviewers to attend a workshop on 'Developing
a protocol', before commencing work. Reviewers are also sent
'Practical guidelines for writing a protocol', when their
title is accepted.
At least two editors/external referees evaluate the protocol
using a refereeing checklist and a form for providing
comment. They are asked to return completed assessments
within four weeks. Comments are forwarded by the review
group co-ordinator to the contact reviewer. Following any
necessary revisions, and after approval by the refereeing
editor, protocols are submitted to the CDSR. Once the
protocol has been accepted, it must be sent to the editorial
base electronically (in Revman).
Reviewers are aware of the identity and contact details of
the editors who comment on their protocols and, in the event
of a difference in opinion, are free to engage in discussion
with them to establish a solution.
Copy-editing of protocols is done at the editorial base and
reviewers sent are asked to approve the final version prior
to publication on CDSR.
Reviews should be submitted within twelve months of the
protocol being accepted for publication on CDSR.
Reviewers are sent a copy of 'Practical guidelines for
writing a review', once their protocol has been accepted.
Advice on specific problems/queries is available from the
editorial base. The complete review is forwarded to the
editorial team and evaluated by the same editors/external
referees (minimum 2). External referees might be requested
for advice when deemed necessary. The refereeing editor
summarises the comments of the referees and outlines
expected revisions. At this stage editors/external reviewers
will randomly check a sample of the included trials to
ensure that data have been extracted correctly and quality
of the included /excluded studies has been assessed
adequately. Following any necessary revisions and approval
by the refereeing editor, the completed review is submitted
to the CDSR. The editorial process to referee a review takes
four weeks; the whole process from the formal submission of
a review, feedback of comments, making revisions/addressing
comments, to receiving overall editorial approval will take
approximately twelve months. Reviewers are aware of the
identity and contact details of the editors who comment on
their reviews and in the event of a different opinion, are
free to engage in discussion with them to establish a
solution. Copy-editing of reviews is done at the editorial
base and reviewers sent are asked to approve the final
version prior to publication on CDSR.
Authors are advised of appropriate trials and are asked to
examine reviews on bienual basis with a view to updating
them. If no new trials have been identified, and no changes
are desired by the editorial base or the reviewer, then the
review will be updated as it stands. If changes are required,
reviewers have nine months in which to update the review.
Revised reviews are edited by a minimum of two editors and a
statistician prior to re-publication. Reviews that include
preliminary data from on-going trials are required to take
subsequent data into account within nine months of the
publication of the data. Revised reviews will be edited by
two editors and a statistician as above.
Reviewers are free to update reviews more often than once
per two years if they wish.
It is likely that, in the future, reviews will need to be
updated in the light of comments received through the 'Comments
and criticisms' facility on the Cochrane Library. It is
expected that reviewers will be obliged to provide a
response to criticism, and, if significant changes were made
to the review as a result, the revised review would be
subjected to the same editorial requirements as an updated
review.
The
Fertility Regulation Group publishes a newsletter once a
year for their reviewers, peer reviewers, handsearchers,
special advisers, their funding agencies and their editors.
Persons who are interested in receiving the newsletter
should contact the editorial office in Leiden.
References
Still
in progress
LINKS
WITH OTHER COLLABORATIVE REVIEW GROUPS:
Menstrual Disorders and Subfertility Group ( Paul O'Brien )
Pregnancy and Childbirth Group ( Frans Helmerhorst )
CO-PUBLICATION
Reviewers may wish to seek co-publication of Cochrane
Reviews in peer-reviewed medical journals, particularly in
those journals that have expressed enthusiasm for
co-publication of Cochrane Reviews.
For
the Cochrane Collaboration, there is one essential condition
of co-publication: Cochrane Reviews must remain free for
dissemination in any and all media, without restriction from
any of them. To ensure this, Cochrane reviewers grant the
Collaboration world-wide licences for these activities, and
do not sign over exclusive copyright to any journal or other
publisher. A journal is free to request a non-exclusive
copyright that permits it to publish and re-publish a review,
but this cannot restrict the publication of the review by
the Cochrane Collaboration in whatever form the
Collaboration feels appropriate.
Reviewers are strongly discouraged from publishing Cochrane
Reviews in journals before they are ready for publication in
CDSR. This applies particularly to Centre directors and
editors of Review Groups. However, journals will sometimes
insist that the publication of the review in CDSR should not
precede publication in print. When this is the case,
reviewers should submit a review for publication in the
journal after agreement from their CRG editor and before
publication in CDSR. Publication in print should not be
subject to lengthy production times, and reviewers should
not unduly delay publication of a Cochrane Review either
because of delays from a journal or in order to resubmit
their review to another journal. Journals can also request
revision of a review for editorial or content reasons.
External peer review provided by journals may enhance the
value of the review and should be welcomed. Journals
generally may require shorter reviews than those published
in CDSR. Selective shortening of reviews may be appropriate,
but there should not be any substantive differences between
the review as published in the journal and CDSR.
If a
review is published in a journal, it should be noted that a
fuller and maintained version of the review is available in
CDSR. Typically, this should be done by including a
statement such as the following in the introduction: 'A more
detailed review will be published and updated in the
Cochrane Database of Systematic Reviews.Reference'.
The
reference should be to the protocol for the review published
in CDSR. A similar statement should be included in the
introduction if a review is published in CDSR prior to
publishing a version of the review in a journal. After a
version of a Cochrane Review has been published in a
journal, a reference to the journal publication must be
added under the heading.
'Other
published versions of this review'.
Reviewers are also encouraged to add the following statement
to versions of Cochrane Reviews that are published in
journals.
'A version of this review has been published in The Cochrane
Library. Cochrane systematic reviews are regularly updated
to include new research, and in response to comments and
criticisms from readers. If you wish to comment on this, or
other Cochrane reviews of interventions for XXX, please send
it to XXX'.
Review
Groups may wish to establish a policy on the person to whom
comments should be sent. Reviewers whose primary affiliation
is a Cochrane entity should include the following sentence
when publishing an article that is not about the Cochrane
Collaboration or does not reflect official policy:
"The views expressed in this article represent those of the
authors and are not necessarily the views or the official
policy of the Cochrane Collaboration".
In addition, the following modification of the disclaimer
published in The Cochrane Library should be added to
Cochrane Reviews published in journals.
"The
results of a Cochrane Review can be interpreted differently,
depending on people's perspectives and circumstances. Please
consider the conclusions presented carefully. They are the
opinions of review authors, and are not necessarily shared
by the Cochrane Collaboration."
The
passage below can be provided to journal editors upon
submission of a review for publication, and the letter of
submission should be copied to the CRG editors for
information. This policy and procedure may be new to some
journal editors and may require direct discussion with the
journal editor. The CRG editors should be informed of any
problems encountered in this process. The following passage
is suggested for inclusion in letters of submission to
journal editors:
"This systematic review has been prepared under the aegis of
the Cochrane Collaboration, an international organisation
that aims to help people make well-informed decisions about
healthcare by preparing, maintaining and promoting the
accessibility of systematic reviews of the effects of
healthcare interventions."
The
Collaboration's publication policy permits journals to
publish reviews, with priority if required, but permits the
Cochrane Collaboration also to publish and disseminate such
reviews. Cochrane Reviews cannot be subject to the exclusive
copyright requested by some journals.
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